WO2024067344A1 - 特异性识别light的抗体及其应用 - Google Patents

特异性识别light的抗体及其应用 Download PDF

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WO2024067344A1
WO2024067344A1 PCT/CN2023/120362 CN2023120362W WO2024067344A1 WO 2024067344 A1 WO2024067344 A1 WO 2024067344A1 CN 2023120362 W CN2023120362 W CN 2023120362W WO 2024067344 A1 WO2024067344 A1 WO 2024067344A1
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seq
amino acid
acid sequence
variant
light
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PCT/CN2023/120362
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French (fr)
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张淼旻
王国武
于德彬
崔静澜
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舒泰神（北京）生物制药股份有限公司
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Publication of WO2024067344A1 publication Critical patent/WO2024067344A1/zh

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants

Definitions

  • the present invention relates to antibodies that specifically recognize LIGHT, and methods for preparing and using the antibodies, including methods for using the antibodies to treat diseases and/or conditions caused by LIGHT signaling pathway disorders, such as autoimmune diseases and/or inflammatory diseases.
  • LIGHT a lymphotoxin-like receptor that can be expressed on T lymphocytes and competes with herpes simplex virus glycoprotein D for binding to HVEM
  • TNFSF tumor necrosis factor superfamily
  • TNFSF14 tumor necrosis factor superfamily member 14
  • CD258 is a type II transmembrane protein containing 240 amino acids that can form homotrimers on the cell surface.
  • the trimeric structure of LIGHT enables it to aggregate cell surface receptors that interact with it, thereby initiating the activation of costimulatory signaling pathways (Bobmer et al., 2002, Trends Biochem. Sci. 27, 19–26).
  • cytoplasmic LIGHT also known as free LIGHT
  • membrane-bound LIGHT also known as cell surface LIGHT
  • LIGHT is not expressed on naive T cells, but is upregulated in activated T cells. LIGHT is expressed on the surface of T cells in a strictly regulated manner after activation, appearing within 4 hours, reaching a peak at 12-24 hours, and disappearing at 48 hours (Castellano et al., 2002, J Biol Chem 277 42841-51). Activation of CD8+ T cells upregulates the expression of LIGHT more than CD4+ T cells. LIGHT is also constitutively expressed on the surface of immature dendritic cells (DC) at detectable levels (Tamada et al., 2000, J Immunol 164 4105-10). LIGHT is also expressed on natural killer (NK) cells and monocytes (Cohavy et al., 2005, J Immunol 174 646-53).
  • DC immature dendritic cells
  • LIGHT binds to three different receptors: lymphotoxin beta receptor (LT ⁇ R) (Crowe et al., 1994, Science 264707-10, Browning et al., 1997, J Immunol 159 3288-98), herpes simplex virus entry mediator (HVEM) (Montgomery et al., 1996, Cell 87(3)427-36) and decoy receptor 3 (DcR3) (Yu et al., 1999, J Biol Chem 274 13733-6). Mutations of amino acids at positions 119 and 174 in the LIGHT sequence can abolish its ability to bind to HVEM and LT ⁇ R receptors (Rooney et al., 2000, J. Biol. Chem.
  • LT ⁇ R is present on the surface of epithelial cells, stromal cells, immature DCs, and myeloid cells, but is not expressed in lymphocytes (Giles et al., 2018, Front Immunol. 9:2585). LT ⁇ R signaling induces genes involved in proinflammatory responses, including activation of MIP-1/2, adhesion molecules, and chemokines (Dejardin E et al., 2002, Immunity. 17(4):525). In addition, studies have reported that LIGHT-LT ⁇ R signaling controls lipid balance and plays a role in dyslipidemia (Combes JL et al., 2007, J Exp Med. 204(8):1757–1764).
  • LIGHT-LT ⁇ R interactions are considered to be an integral part of the development and maintenance of lymphoid structures (Lu et al., 2014, Front Immunol. 5:47). Scheu et al. found that the absence of LIGHT and LT ⁇ in mice led to the destruction of all secondary lymphoid structures (Scheu et al., 2002, J Exp Med 195:1613-1624).
  • LT ⁇ R was shown to associate with a signaling complex including TRAF2, TRAF3, and inhibitor of ⁇ B (I ⁇ B) kinase complex (IKK).
  • I ⁇ B ⁇ B kinase complex
  • the LIGHT-LT ⁇ R interaction mediates the activation of c-Jun N-terminal kinase (JNK), activator protein-1 (AP-1), and nuclear factor- ⁇ B (NF- ⁇ B) in a TRAF2-dependent manner (Kim WJ et al., 2005, Immunology. 114(2):272–279.).
  • JNK c-Jun N-terminal kinase
  • AP-1 activator protein-1
  • NF- ⁇ B nuclear factor- ⁇ B
  • LIGHT-LT ⁇ R signaling The effects of LIGHT-LT ⁇ R signaling are wide-ranging.
  • the function of LIGHT-LT ⁇ R can positively regulate and support anti-tumor immune responses, including increasing the sensitivity of cancer cells to immune responses, repairing disordered tumor vasculature, and supporting cell migration and infiltration of effector cells into tumors (Joseph G. et al., Frontiers in Immonology, 2020).
  • studies by Conlon TM et al. have demonstrated that therapeutic inhibition of LT ⁇ R signaling can restore lung structure from smoking-induced emphysema and airway fibrosis.
  • Blocking the effects of LT ⁇ R signaling can block the formation of iBALT, apoptosis of alveolar epithelial cells, and restart endogenous Wnt/ ⁇ -catenin-driven alveolar regeneration (Conlon TM et al., 2020, Nature. 588(7836):151-156).
  • HVEM Herpes simplex virus entry mediator
  • TNFRSF14 tumor necrosis factor receptor superfamily member 14
  • TNFRSF14 tumor necrosis factor receptor superfamily member 14
  • HVEM can interact with a variety of different ligands, which transmit activation or inhibition signals to the downstream by binding to the CRD domain of HVEM. Some of these ligands deliver co-stimulatory signals, such as LIGHT and LT ⁇ ; others deliver co-inhibitory signals, such as CD160, glycoprotein D (gD), and BTLA (Murphy et al., Annu Rev Immunol. 28:389, 2010).
  • co-stimulatory signals such as LIGHT and LT ⁇
  • co-inhibitory signals such as CD160, glycoprotein D (gD), and BTLA (Murphy et al., Annu Rev Immunol. 28:389, 2010).
  • the CRD2 and CRD3 domains of HVEM interact with LIGHT (Ware et al., 2008, Immunol. Rev.
  • BTLA and CD160 bind to CRD1 and CRD2 of HVEM and compete with HSV gD binding (Compaan et al., 2005, J. Biol. Chem. 280, 39553–39561.). Studies have reported that the loss of the CRD1 domain results in the transmission of co-stimulatory signals of HVEM-Ig. This suggests that CRD1 is essential for the inhibitory signaling induced by recombinant HVEM-Ig fusion protein (Adams et al., 2002, Am. J. Transplant. 2, 12-18).
  • HVEM The interaction of LIGHT with HVEM is responsible for the major immunostimulatory properties of LIGHT (Steinberg et al., 2011, Immunol Rev. 244:169–87).
  • HVEM expressed on lymphocytes, NK cells, smooth muscle, and epithelial cells, acts as an important T cell stimulator, leading to T cell activation, proliferation, and survival (Ware CF et al., 2011, Curr Opin Immunol 23:627-31).
  • HVEM is required for the co-stimulatory effect of LIGHT in a CD28-independent T cell-to-T cell manner to activate T effector cells. This pro-inflammatory interaction increases the expression of the Th1 cytokines IFN ⁇ and GM-CSF.
  • HVEM can induce the recruitment of TRAFs, including TRAF2, and the activation of NF- ⁇ B and JNK/AP-1 transcription factors, which contribute to T cell survival in vivo.
  • HVEM can also trigger NK cells to produce IFN ⁇ through LIGHT-mediated nuclear factor- ⁇ B (NF- ⁇ B) RelA/p50 signaling (Fan et al., 2006, Blood 107:1342-51).
  • LIGHT produced by tumor-sensing NK cells is an important component of the NK-DC tandem that occurs during the initiation of a new antitumor response (Holmes et al., 2014, Proc Natl Acad Sci USA. 111:E5688–96). Therefore, LIGHT-HVEM-mediated T cell co-stimulation and NK-DC tandem play an important role in generating antitumor immunity in a therapeutic setting.
  • Patent application WO2008027338A2 discloses an antibody capable of specifically binding to an hLIGHT polypeptide, and a method for treating an hLIGHT-mediated disease in an individual, comprising administering an antibody, such as a fully humanized antibody, that specifically binds to an hLIGHT polypeptide to the individual.
  • LIGHT can activate T cell or innate immune cell-mediated inflammatory responses by binding to HVEM or LT ⁇ R receptors, causing autoimmune diseases and/or inflammatory diseases. Therefore, using therapeutic antibodies to antagonize LIGHT can inhibit the immune response induced by this signaling pathway and provide new treatments for the above-mentioned related diseases.
  • an isolated anti-LIGHT antibody comprising a heavy chain variable domain ( VH ), the VH comprising: a heavy chain complementary determining region (HC-CDR) 1 comprising GYFIN (SEQ ID NO: 1); HC-CDR2 comprising RIYPYNVX1TFYNQNFKG (SEQ ID NO: 45), wherein X1 is D or N; and HC-CDR3 comprising GTHYYGSSGAMDY (SEQ ID NO: 16); and a light chain variable domain ( VL ), the VL comprising: a light chain complementary determining region (LC-CDR) 1 comprising KASQNVGTAVA (SEQ ID NO: 23); LC-CDR2 comprising SASNRYT (SEQ ID NO: 30); and LC-CDR3 comprising QQYSSYPYT (SEQ ID NO: 37).
  • VH heavy chain variable domain
  • HC-CDR heavy chain complementary determining region
  • HC-CDR2 comprising RIYPYNVX1TFY
  • an isolated anti-LIGHT antibody comprising a VH , wherein the VH comprises: HC-CDR1, comprising the amino acid sequence shown in SEQ ID NO: 1 or a variant thereof, wherein the variant comprises at most about 3 amino acid substitutions; HC-CDR2, comprising the amino acid sequence shown in any one of SEQ ID NOs: 8-9 or a variant thereof, wherein the variant comprises at most about 3 amino acid substitutions; and HC-CDR3, comprising the amino acid sequence shown in SEQ ID NO: 16 or a variant thereof, wherein the variant comprises at most about 3 amino acid substitutions.
  • VL comprises: a LC-CDR1 comprising the amino acid sequence shown in SEQ ID NO:23 or a variant thereof, wherein the variant comprises the substitution of up to about 3 amino acids; a LC-CDR2 comprising the amino acid sequence shown in SEQ ID NO:30 or a variant thereof, wherein the variant comprises the substitution of up to about 3 amino acids; and a LC-CDR3 comprising the amino acid sequence shown in SEQ ID NO:37 or a variant thereof, wherein the variant comprises the substitution of up to about 3 amino acids.
  • an isolated anti-LIGHT antibody comprising: a VH comprising HC-CDR1, HC-CDR2 and HC-CDR3 comprised by the VH as shown in any one of the amino acid sequences of SEQ ID NOs:46-53, and a VL comprising LC-CDR1, LC-CDR2 and LC-CDR3 comprised by the VL as shown in any one of the amino acid sequences of SEQ ID NOs:62-65.
  • an isolated anti-LIGHT antibody comprising: (i) a VH comprising HC-CDR1, HC-CDR2 and HC-CDR3 comprised by the VH as shown in the amino acid sequence of SEQ ID NO:46; and a VL comprising LC-CDR1, LC-CDR2 and LC-CDR3 comprised by the VL as shown in the amino acid sequence of SEQ ID NO:62; (ii) a VH comprising HC-CDR1, HC-CDR2 and HC-CDR3 comprised by the VH as shown in the amino acid sequence of SEQ ID NO:47; and a VL comprising LC-CDR1, LC-CDR2 and LC-CDR3 comprised by the VL as shown in the amino acid sequence of SEQ ID NO:63; (iii) a VH comprising HC-CDR1, HC-CDR2 and HC-CDR3 comprised by the VH as shown in the amino acid sequence of SEQ ID NO:63;
  • an isolated anti-LIGHT antibody comprising: (i) a VH comprising: a HC- CDR1 comprising the amino acid sequence of SEQ ID NO: 1, a HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 8, and a HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 16, or a variant of the VH comprising up to about 5 amino acid substitutions in the HC-CDRs; and a VL comprising: a LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 23, a LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 30, and a LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 37, or a variant of the VL comprising up to about 5 amino acid substitutions in the LC-CDRs; (ii) a VH comprising: a HC- CDR1 comprising the amino acid sequence of SEQ ID NO: 1, a HC
  • a variant of H comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L comprising: LC- CDR1 comprising the amino acid sequence of SEQ ID NO:23, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:30, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:37, or a variant of the V L comprising up to about 5 amino acid substitutions in its LC-CDRs.
  • any one of the isolated anti-LIGHT antibodies described above comprises: a VH comprising an amino acid sequence as shown in any one of SEQ ID NOs:46-53 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence as shown in any one of SEQ ID NOs:46-53; and a VL comprising an amino acid sequence as shown in any one of SEQ ID NOs:62-65 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence as shown in any one of SEQ ID NOs:62-65.
  • an isolated anti-LIGHT antibody comprising: (i) a VH comprising an amino acid sequence of SEQ ID NO:46 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:46; and a VL comprising an amino acid sequence of SEQ ID NO:62 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:62; (ii) a VH comprising an amino acid sequence of SEQ ID NO:47 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:47; and a VL comprising an amino acid sequence of SEQ ID NO:63 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:63; (iii) a VH comprising an amino acid sequence of SEQ ID NO:48 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino
  • a VH comprising an amino acid sequence of SEQ ID NO:50 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:50; and a VL comprising an amino acid sequence of SEQ ID NO:63 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:63; (vi) a VH comprising an amino acid sequence of SEQ ID NO:47 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:47; and a VL comprising an amino acid sequence of SEQ ID NO:64 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:65.
  • an isolated anti-LIGHT antibody comprising: (i) a VH comprising HC-CDR1, HC-CDR2 and HC-CDR3 comprised by the VH as shown in the amino acid sequence of SEQ ID NO:54; and a VL comprising LC-CDR1, LC-CDR2 and LC-CDR3 comprised by the VL as shown in the amino acid sequence of SEQ ID NO:66.
  • an isolated anti-LIGHT antibody comprising: (i) a VH comprising: a HC-CDR1 comprising the amino acid sequence of SEQ ID NO:2, a HC-CDR2 comprising the amino acid sequence of SEQ ID NO:10, and a HC-CDR3 comprising the amino acid sequence of SEQ ID NO:17, or a variant of the VH comprising up to about 5 amino acid substitutions in its HC-CDRs; and a VL comprising: a LC -CDR1 comprising the amino acid sequence of SEQ ID NO:24, a LC-CDR2 comprising the amino acid sequence of SEQ ID NO:31, and a LC-CDR3 comprising the amino acid sequence of SEQ ID NO:38, or a variant of the VL comprising up to about 5 amino acid substitutions in its LC-CDRs.
  • any isolated anti-LIGHT antibody as described above comprises: a VH comprising the amino acid sequence shown in SEQ ID NO:54 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO:54; and a VL comprising the amino acid sequence shown in SEQ ID NO:66 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO:66.
  • an isolated anti-LIGHT antibody comprising: (i) a VH comprising HC-CDR1, HC-CDR2 and HC-CDR3 comprised by the VH as shown in the amino acid sequence of SEQ ID NO:55; and a VL comprising LC-CDR1, LC-CDR2 and LC-CDR3 comprised by the VL as shown in the amino acid sequence of SEQ ID NO:67.
  • an isolated anti-LIGHT antibody comprising: (i) a VH comprising: a HC-CDR1 comprising the amino acid sequence of SEQ ID NO:2, a HC-CDR2 comprising the amino acid sequence of SEQ ID NO:10, and a HC-CDR3 comprising the amino acid sequence of SEQ ID NO:17, or a variant of the VH comprising up to about 5 amino acid substitutions in its HC-CDRs; and a VL comprising: a LC -CDR1 comprising the amino acid sequence of SEQ ID NO:25, a LC-CDR2 comprising the amino acid sequence of SEQ ID NO:31, and a LC-CDR3 comprising the amino acid sequence of SEQ ID NO:39, or a variant of the VL comprising up to about 5 amino acid substitutions in its LC-CDRs.
  • any isolated anti-LIGHT antibody as described above comprises: a VH comprising the amino acid sequence shown in SEQ ID NO:55 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO:55; and a VL comprising the amino acid sequence shown in SEQ ID NO:67 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO:67.
  • an isolated anti-LIGHT antibody comprising: (i) a VH comprising HC-CDR1, HC-CDR2 and HC-CDR3 comprised by the VH as shown in the amino acid sequence of SEQ ID NO:56; and a VL comprising LC-CDR1, LC-CDR2 and LC-CDR3 comprised by the VL as shown in the amino acid sequence of SEQ ID NO:68.
  • an isolated anti-LIGHT antibody comprising: (i) a VH comprising: a HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 3, a HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 11, and a HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 18, or a variant of the VH comprising at most about 5 HC-CDRs; and a V L comprising: a LC-CDR1 comprising the amino acid sequence of SEQ ID NO:26, a LC-CDR2 comprising the amino acid sequence of SEQ ID NO:32, and a LC-CDR3 comprising the amino acid sequence of SEQ ID NO:40, or a variant of said V L comprising up to about 5 amino acid substitutions in its LC-CDRs.
  • any isolated anti-LIGHT antibody as described above comprises: a VH comprising the amino acid sequence shown in SEQ ID NO:56 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO:56; and a VL comprising the amino acid sequence shown in SEQ ID NO:68 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO:68.
  • an isolated anti-LIGHT antibody comprising: (i) a VH comprising HC-CDR1, HC-CDR2 and HC-CDR3 comprised by the VH as shown in the amino acid sequence of SEQ ID NO:57; and a VL comprising LC-CDR1, LC-CDR2 and LC-CDR3 comprised by the VL as shown in the amino acid sequence of SEQ ID NO:69.
  • an isolated anti-LIGHT antibody comprising: (i) a VH comprising: a HC-CDR1 comprising the amino acid sequence of SEQ ID NO:3, a HC-CDR2 comprising the amino acid sequence of SEQ ID NO:11, and a HC-CDR3 comprising the amino acid sequence of SEQ ID NO:18, or a variant of the VH comprising up to about 5 amino acid substitutions in its HC-CDRs; and a VL comprising: a LC -CDR1 comprising the amino acid sequence of SEQ ID NO:26, a LC-CDR2 comprising the amino acid sequence of SEQ ID NO:32, and a LC-CDR3 comprising the amino acid sequence of SEQ ID NO:41, or a variant of the VL comprising up to about 5 amino acid substitutions in its LC-CDRs.
  • any isolated anti-LIGHT antibody as described above comprises: a VH comprising the amino acid sequence shown in SEQ ID NO:57 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO:57; and a VL comprising the amino acid sequence shown in SEQ ID NO:69 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO:69.
  • an isolated anti-LIGHT antibody comprising: (i) a VH comprising HC-CDR1, HC-CDR2 and HC-CDR3 comprised by the VH as shown in the amino acid sequence of SEQ ID NO:58; and a VL comprising LC-CDR1, LC-CDR2 and LC-CDR3 comprised by the VL as shown in the amino acid sequence of SEQ ID NO:70.
  • an isolated anti-LIGHT antibody comprising: (i) a VH comprising: a HC-CDR1 comprising the amino acid sequence of SEQ ID NO:4, a HC-CDR2 comprising the amino acid sequence of SEQ ID NO:12, and a HC-CDR3 comprising the amino acid sequence of SEQ ID NO:19, or a variant of the VH comprising up to about 5 amino acid substitutions in its HC-CDRs; and a VL comprising: a LC -CDR1 comprising the amino acid sequence of SEQ ID NO:27, a LC-CDR2 comprising the amino acid sequence of SEQ ID NO:33, and a LC-CDR3 comprising the amino acid sequence of SEQ ID NO:42, or a variant of the VL comprising up to about 5 amino acid substitutions in its LC-CDRs.
  • any isolated anti-LIGHT antibody as described above comprises: a VH comprising the amino acid sequence shown in SEQ ID NO:58 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO:58; and a VL comprising the amino acid sequence shown in SEQ ID NO:70 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO:70.
  • an isolated anti-LIGHT antibody comprising: (i) a VH comprising HC-CDR1, HC-CDR2 and HC-CDR3 comprised by the VH as shown in the amino acid sequence of SEQ ID NO:59; and a VL comprising LC-CDR1, LC-CDR2 and LC-CDR3 comprised by the VL as shown in the amino acid sequence of SEQ ID NO:71.
  • an isolated anti-LIGHT antibody comprising: (i) a VH comprising: a HC-CDR1 comprising the amino acid sequence of SEQ ID NO:5, a HC-CDR2 comprising the amino acid sequence of SEQ ID NO:13, and a HC-CDR3 comprising the amino acid sequence of SEQ ID NO:20, or a variant of the VH comprising up to about 5 amino acid substitutions in its HC-CDRs; and a VL comprising: a LC -CDR1 comprising the amino acid sequence of SEQ ID NO:28, a LC-CDR2 comprising the amino acid sequence of SEQ ID NO:34, and a LC-CDR3 comprising the amino acid sequence of SEQ ID NO:43, or a variant of the VL comprising up to about 5 amino acid substitutions in its LC-CDRs.
  • any isolated anti-LIGHT antibody as described above comprises: a VH comprising the amino acid sequence shown in SEQ ID NO:59 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO:59; and a VL comprising the amino acid sequence shown in SEQ ID NO:71 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO:71.
  • an isolated anti-LIGHT antibody comprising a heavy chain variable domain ( VH ), the VH comprising a heavy chain complementary determining region (HC-CDR) 1 comprising DHIMN (SEQ ID NO:6); HC-CDR2 comprising RIYPVSGETNYNQKFMG (SEQ ID NO:14); and HC-CDR3 comprising GSYYWNAMDY (SEQ ID NO:21); and a light chain variable domain ( VL ), the VL comprising: a light chain complementary determining region (LC-CDR) 1 comprising KASQSVDFDGDSYMN (SEQ ID NO:29) or KASQSVDFDGESYMN (SEQ ID NO:83); LC-CDR2 comprising SASNLES (SEQ ID NO:35); and LC-CDR3 comprising QQSIEDPWT (SEQ ID NO:43).
  • VH heavy chain variable domain
  • HC-CDR heavy chain complementary determining region 1 comprising DHIMN (SEQ ID NO
  • an isolated anti-LIGHT antibody comprising a VH comprising: an HC-CDR1 comprising the amino acid sequence shown in SEQ ID NO:6 or a variant thereof, wherein the variant comprises up to about 3 amino acid substitutions; an HC-CDR2 comprising the amino acid sequence shown in SEQ ID NO:14 or a variant thereof, wherein the variant comprises up to about 3 amino acid substitutions; and an HC-CDR3 comprising the amino acid sequence shown in SEQ ID NO:21 or a variant thereof, wherein the variant comprises up to about 3 amino acid substitutions; and a VL comprising: an LC-CDR1 comprising the amino acid sequence shown in any one of SEQ ID NOs:29 or 83 or a variant thereof, wherein the variant comprises up to about 3 amino acid substitutions; an LC-CDR2 comprising the amino acid sequence shown in SEQ ID NO:35 or a variant thereof, wherein the variant comprises up to about 3 amino acid substitutions; and an LC-CDR3 comprising
  • an isolated anti-LIGHT antibody comprising: a VH comprising HC-CDR1, HC-CDR2 and HC-CDR3 comprised by the VH as shown in any one of the amino acid sequences of SEQ ID NOs: 60, 84-85, and a VL comprising LC-CDR1, LC-CDR2 and LC-CDR3 comprised by the VL as shown in any one of the amino acid sequences of SEQ ID NOs: 72, 86-91.
  • an isolated anti-LIGHT antibody comprising: (i) a VH comprising HC-CDR1, HC-CDR2 and HC-CDR3 as shown in the amino acid sequence of SEQ ID NO: 60; and a VL comprising and LC-CDR1, LC-CDR2 and LC-CDR3 contained in the V L as shown in the amino acid sequence of SEQ ID NO: 72; (ii) V H comprising HC-CDR1, HC-CDR2 and HC-CDR3 contained in the V H as shown in the amino acid sequence of SEQ ID NO: 84; and V L comprising LC-CDR1, LC-CDR2 and LC-CDR3 contained in the V L as shown in the amino acid sequence of SEQ ID NO: 86; (iii) V H comprising HC-CDR1, HC-CDR2 and HC-CDR3 contained in the V H as shown in the amino acid sequence of SEQ ID NO: 85; and V L comprising
  • an isolated anti-LIGHT antibody comprising: (i) a VH comprising: a HC- CDR1 comprising the amino acid sequence of SEQ ID NO:6, a HC-CDR2 comprising the amino acid sequence of SEQ ID NO:14, and a HC-CDR3 comprising the amino acid sequence of SEQ ID NO:21, or a variant of the VH comprising up to about 5 amino acid substitutions in the HC-CDRs; and a VL comprising: a LC-CDR1 comprising the amino acid sequence of SEQ ID NO:29, a LC-CDR2 comprising the amino acid sequence of SEQ ID NO:35, and a LC-CDR3 comprising the amino acid sequence of SEQ ID NO:43, or a variant of the VL comprising up to about 5 amino acid substitutions in the LC-CDRs; (ii) a VH comprising: a HC- CDR1 comprising the amino acid sequence of SEQ ID NO:6,
  • a variant of H comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L comprising: LC- CDR1 comprising the amino acid sequence of SEQ ID NO:83, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:35, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:43, or a variant of the V L comprising up to about 5 amino acid substitutions in its LC-CDRs.
  • any isolated anti-LIGHT antibody as described above comprises: a VH comprising an amino acid sequence as shown in any one of SEQ ID NOs: 60, 84-85 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence as shown in any one of SEQ ID NOs: 60, 84-85; and a VL comprising an amino acid sequence as shown in any one of SEQ ID NOs: 72, 86-91 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence as shown in any one of SEQ ID NOs: 72, 86-91.
  • any of the isolated anti-LIGHT antibodies described above comprises: (i) a VH comprising the amino acid sequence of SEQ ID NO:60 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:60; and a VL comprising the amino acid sequence of SEQ ID NO:72 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:72; (ii) a VH comprising the amino acid sequence of SEQ ID NO: 84 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:84; and VL , comprising the amino acid sequence of SEQ ID NO:86 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:86; (iii) VH , comprising the amino acid sequence of SEQ ID NO:85 or a variant thereof, said variant having at least about 80% sequence identity with
  • an isolated anti-LIGHT antibody comprising a heavy chain variable domain ( VH ), the VH comprising: a heavy chain complementary determining region (HC-CDR) 1 comprising SYNVH (SEQ ID NO:7); HC-CDR2 comprising AVYPGNGDTSYNQKFKG (SEQ ID NO:15); and HC-CDR3 comprising GSYYYTSSYFDH (SEQ ID NO:22); and a light chain variable domain ( VL ), the VL comprising: a light chain complementary determining region (LC-CDR) 1 comprising KASQSVDFDGDSYMN (SEQ ID NO:29); LC-CDR2 comprising TASNLES (SEQ ID NO:36); and LC-CDR3 comprising QQSYEDPFT (SEQ ID NO:44).
  • VH heavy chain variable domain
  • HC-CDR heavy chain complementary determining region 1 comprising SYNVH
  • HC-CDR2 comprising AVYPGNGDTSY
  • an isolated anti-LIGHT antibody comprising: a VH comprising HC-CDR1, HC-CDR2 and HC-CDR3 comprised by the VH as shown in any one of the amino acid sequences of SEQ ID NOs:61, 92-94; and a VL comprising LC-CDR1, LC-CDR2 and LC-CDR3 comprised by the VL as shown in any one of the amino acid sequences of SEQ ID NOs :73, 95-99.
  • an isolated anti-LIGHT antibody comprising: (i) a VH comprising HC-CDR1, HC-CDR2 and HC-CDR3 comprised by the VH as shown in the amino acid sequence of SEQ ID NO:61; and a VL comprising LC-CDR1, LC-CDR2 and LC-CDR3 comprised by the VL as shown in the amino acid sequence of SEQ ID NO:73.
  • an isolated anti-LIGHT antibody comprising: (i) a VH comprising: a HC-CDR1 comprising the amino acid sequence of SEQ ID NO:7, a HC-CDR2 comprising the amino acid sequence of SEQ ID NO:15, and a HC-CDR3 comprising the amino acid sequence of SEQ ID NO:22, or a variant of the VH comprising up to about 5 amino acid substitutions in its HC-CDRs; and a VL comprising: a LC -CDR1 comprising the amino acid sequence of SEQ ID NO:29, a LC-CDR2 comprising the amino acid sequence of SEQ ID NO:36, and a LC-CDR3 comprising the amino acid sequence of SEQ ID NO:44, or a variant of the VL comprising up to about 5 amino acid substitutions in its LC-CDRs.
  • any isolated anti-LIGHT antibody as described above comprises: a VH comprising an amino acid sequence as shown in any one of SEQ ID NOs: 61, 92-94 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence as shown in any one of SEQ ID NOs: 61, 92-94; and a VL comprising an amino acid sequence as shown in any one of SEQ ID NOs: 73, 95-99 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence as shown in any one of SEQ ID NOs: 73, 95-99.
  • any of the isolated anti-LIGHT antibodies described above comprises: (i) a VH comprising an amino acid sequence as set forth in SEQ ID NO:61 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence as set forth in SEQ ID NO:61; and a VL comprising an amino acid sequence as set forth in SEQ ID NO:73 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence as set forth in SEQ ID NO:73; (ii) a VH comprising an amino acid sequence as set forth in SEQ ID NO:92 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence as set forth in SEQ ID NO:92; and a VL comprising an amino acid sequence as set forth in SEQ ID NO:95 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence as set forth in SEQ ID NO:95; (iii) a VH comprising an amino acid sequence as set forth in SEQ ID NO:
  • the isolated anti-LIGHT antibody binds to human LIGHT with a Kd value of 0.1 pM to about 10 nM.
  • an isolated anti-LIGHT antibody is provided that competes with any of the above isolated anti-LIGHT antibodies for specific binding to LIGHT. In some embodiments, an isolated anti-LIGHT antibody is provided that specifically binds to the same epitope as any of the above isolated anti-LIGHT antibodies.
  • any of the anti-LIGHT antibodies separated as described above, the anti-LIGHT antibody separated comprises an Fc fragment.
  • the anti-LIGHT antibody separated is a full-length IgG antibody.
  • the anti-LIGHT antibody separated is a full-length IgG1, IgG2, IgG3 or IgG4 antibody.
  • the anti-LIGHT antibody separated is a chimeric, fully human or humanized antibody.
  • the anti-LIGHT antibody separated is an antigen-binding fragment selected from Fab, Fab', F(ab)' 2 , Fab'-SH, single-chain Fv (scFv), Fv fragment, dAb, Fd, nanobody, double-chain antibody (diabody) and linear antibody.
  • an isolated nucleic acid molecule is provided, the nucleic acid molecule encoding any anti-LIGHT antibody as described above.
  • a vector is provided, the vector comprising any nucleic acid molecule as described above.
  • a host cell is provided, the host cell comprising any anti-LIGHT antibody as described above, any nucleic acid molecule as described above, or any vector as described above.
  • a method for preparing an anti-LIGHT antibody comprising: a) culturing any of the above host cells under conditions that can effectively express the anti-LIGHT antibody; and b) obtaining the expressed anti-LIGHT antibody from the host cell.
  • a method for treating a desired individual disease or condition comprising administering to the individual an effective amount of any anti-LIGHT antibody as described above.
  • the use of any anti-LIGHT antibody as described above in the preparation of a pharmaceutical composition for treating a desired individual disease or condition is provided.
  • the use of any anti-LIGHT antibody as described above or a pharmaceutical composition comprising an anti-LIGHT antibody in the preparation of a medicament for treating a disease or condition is provided.
  • the disease or condition is related to the LIGHT signaling pathway, including autoimmune diseases and/or inflammatory diseases or conditions.
  • the disease or condition is selected from, for example, inflammatory bowel disease (IBD), Crohn's disease, ulcerative colitis, ankylosing spondylitis, atopic dermatitis, rheumatoid arthritis, bronchiolitis, transplant rejection, allograft rejection, graft-versus-host disease (GVHD), asthma, eosinophilic esophagitis, acute respiratory distress syndrome (ARDS), chronic heart failure, chronic obstructive pulmonary disease (COPD), septic shock, fibrotic diseases, skin fibrosis, idiopathic pulmonary fibrosis, renal fibrosis, chronic kidney disease, systemic sclerosis, multiple sclerosis, Sjögren's syndrome, lupus, airway inflammation, psoriasis, hepatitis, celiac disease, primary biliary cirrhosis, autoimmune hemolytic anemia, autoimmune neonatal thrombocytopenia, idiopathic thro
  • compositions, kits, and manufactured products comprising any of the anti-LIGHT antibodies described above.
  • Figure 1 shows the binding affinity of chimeric anti-LIGHT antibodies to human LIGHT analyzed by ELISA.
  • Figure 1A shows the binding affinity of exemplary chimeric anti-LIGHT antibodies LT-m17 and LT-m18 to human LIGHT.
  • Figure 1B shows the binding affinity of exemplary chimeric anti-LIGHT antibodies LT-m31, LT-m33, and LT-m37 to human LIGHT.
  • Figure 1C shows the binding affinity of exemplary chimeric anti-LIGHT antibodies LT-m55, LT-m58, LT-m64, and LT-m85 to human LIGHT.
  • Figure 2 shows the cross-binding activity of chimeric anti-LIGHT antibodies with cynomolgus monkey LIGHT analyzed by ELISA.
  • Figure 2A shows the cross-binding activity of exemplary chimeric anti-LIGHT antibodies LT-m17 and LT-m18 with cynomolgus monkey LIGHT.
  • Figure 2B shows the cross-binding activity of exemplary chimeric anti-LIGHT antibodies LT-m31, LT-m33, LT-m37 with cynomolgus monkey LIGHT.
  • Figure 2C shows the cross-binding activity of exemplary chimeric anti-LIGHT antibodies LT-m55, LT-m58, LT-m64, LT-m85 with cynomolgus monkey LIGHT.
  • Figure 3A shows the inhibitory activity of exemplary chimeric anti-LIGHT antibodies LT-m17, LT-m31, LT-m33, and LT-m37 on free LIGHT activation of the LT ⁇ R reporter gene.
  • Figure 3B shows the inhibitory activity of exemplary chimeric anti-LIGHT antibodies LT-m55, LT-m58, LT-m64, and LT-m85 on free LIGHT activation of the LT ⁇ R reporter gene.
  • Figure 4A shows the inhibitory activity of exemplary chimeric anti-LIGHT antibodies LT-m17, LT-m31, LT-m33, and LT-m37 on cell LIGHT activation of LT ⁇ R reporter genes.
  • Figure 4B shows the inhibitory activity of exemplary chimeric anti-LIGHT antibodies LT-m55, LT-m58, and LT-m64 on cell LIGHT activation of LT ⁇ R reporter genes.
  • Figure 4C shows the inhibitory activity of exemplary chimeric anti-LIGHT antibody LT-m85 on cell LIGHT activation of LT ⁇ R reporter genes.
  • Figure 5A shows the inhibitory activity of exemplary chimeric anti-LIGHT antibodies LT-m17, LT-m31, LT-m33, and LT-m37 on free LIGHT activation of the HVEM reporter gene.
  • Figure 5B shows the inhibitory activity of exemplary chimeric anti-LIGHT antibodies LT-m55, LT-m64, and LT-m85 on free LIGHT activation of the HVEM reporter gene.
  • Figure 5C shows the inhibitory activity of exemplary chimeric anti-LIGHT antibody LT-m58 on free LIGHT activation of the HVEM reporter gene.
  • Figure 6 shows the binding affinity of humanized anti-LIGHT antibodies to human LIGHT analyzed by ELISA.
  • Figure 6A shows the binding affinity of exemplary humanized anti-LIGHT antibodies hum_LT-m37-1 to hum_LT-m37-6 to human LIGHT.
  • Figure 6B shows the binding affinity of exemplary humanized anti-LIGHT antibodies hum_LT-m37-7 to hum_LT-m37-12 to human LIGHT.
  • Figure 6C shows the binding affinity of exemplary humanized anti-LIGHT antibodies hum_LT-m37-13 to hum_LT-m37-16 to human LIGHT.
  • Figure 7 shows the activity of humanized anti-LIGHT antibodies in blocking the binding of LIGHT to LT ⁇ R analyzed by ELISA.
  • Figure 7A shows the activity of exemplary humanized anti-LIGHT antibodies hum_LT-m37-1, hum_LT-m37-2, hum_LT-m37-4, hum_LT-m37-9 in blocking the binding of LIGHT to LT ⁇ R analyzed by ELISA.
  • Figure 7B shows the activity of exemplary humanized anti-LIGHT antibodies hum_LT-m37-5, hum_LT-m37-6, hum_LT-m37-7, hum_LT-m37-8, hum_LT-m37-11, hum_LT-m37-12 in blocking the binding of LIGHT to LT ⁇ R analyzed by ELISA.
  • FIG. 7C shows the activity of exemplary humanized anti-LIGHT antibodies hum_LT-m37-13, hum_LT-m37-14, hum_LT-m37-15, hum_LT-m37-16 in blocking the binding of LIGHT to LT ⁇ R as analyzed by ELISA.
  • Figure 8A shows the inhibitory activity of exemplary humanized anti-LIGHT antibodies hum_LT-m37-1 to hum_LT-m37-6 on free LIGHT activation of LT ⁇ R reporter gene.
  • Figure 8B shows the inhibitory activity of exemplary humanized anti-LIGHT antibodies hum_LT-m37-7 to hum_LT-m37-12 on free LIGHT activation of LT ⁇ R reporter gene.
  • Figure 8C shows the inhibitory activity of exemplary humanized anti-LIGHT antibodies hum_LT-m37-13 to hum_LT-m37-16 on free LIGHT activation of LT ⁇ R reporter gene.
  • FIG9A shows the inhibitory activity of exemplary humanized anti-LIGHT antibodies hum_LT-m37-1 to hum_LT-m37-6 on cellular LIGHT activation of LT ⁇ R reporter gene.
  • FIG9B shows the inhibitory activity of exemplary humanized anti-LIGHT antibodies hum_LT-m37-7 to hum_LT- m37-12 inhibits the activation of LT ⁇ R reporter gene by cell LIGHT.
  • Figure 9C shows the inhibitory activity of exemplary humanized anti-LIGHT antibodies hum_LT-m37-13 to hum_LT-m37-16 on the activation of LT ⁇ R reporter gene by cell LIGHT.
  • Figure 10A shows the inhibitory activity of exemplary humanized anti-LIGHT antibodies hum_LT-m37-1 to hum_LT-m37-6 on free LIGHT activation of HVEM reporter gene.
  • Figure 10B shows the inhibitory activity of exemplary humanized anti-LIGHT antibodies hum_LT-m37-14, hum_LT-m37-15, and hum_LT-m37-16 on free LIGHT activation of HVEM reporter gene.
  • FIG. 11 shows the inhibitory activity of exemplary humanized anti-LIGHT antibodies hum_LT-m37-13, hum_LT-m37-14, hum_LT-m37-15, and hum_LT-m37-16 on the production of MMP-9 induced by LIGHT in BEAS-2B bronchial epithelial cells.
  • FIG. 12 shows the inhibitory activity of exemplary humanized anti-LIGHT antibodies hum_LT-m37-13, hum_LT-m37-14, hum_LT-m37-15, and hum_LT-m37-16 on the activation and proliferation of CD3+ T cells stimulated by LIGHT.
  • Figure 13 shows the inhibitory activity of exemplary anti-LIGHT antibodies on leukocyte levels in the LPS-induced mouse ARDS model.
  • Figure 13A shows the inhibitory activity of exemplary anti-LIGHT antibodies LT-m17 and hum_LT-m37-12 on total leukocyte levels in the LPS-induced mouse ARDS model.
  • Figure 13B shows the inhibitory activity of exemplary anti-LIGHT antibodies LT-m17 and hum_LT-m37-12 on intermediate cell levels in the LPS-induced mouse ARDS model.
  • Figure 13C shows the inhibitory activity of exemplary anti-LIGHT antibodies LT-m17 and hum_LT-m37-12 on lymphocyte levels in the LPS-induced mouse ARDS model.
  • Figure 13D shows the inhibitory activity of exemplary anti-LIGHT antibodies LT-m17 and hum_LT-m37-12 on neutrophil levels in the LPS-induced mouse ARDS model.
  • the present application provides anti-LIGHT antibody molecules.
  • anti-LIGHT antibody F19 also known as CERC-002, Quisovalimab; Avalo Therapeutics
  • the antibodies in the present application bind to different regions or epitopes of LIGHT, and surprisingly, the antibodies in the present application have been shown to be even more effective than F19 in various biological experiments.
  • anti-LIGHT antibodies provided in the present application include, for example, full-length anti-LIGHT antibodies, anti-LIGHT single-chain antibodies (scFvs), anti-LIGHT Fc fusion proteins, multispecific (such as bispecific) anti-LIGHT antibodies, anti-LIGHT immunoconjugates and the like.
  • an anti-LIGHT antibody comprising: a heavy chain variable domain ( VH ), the VH comprising: a heavy chain complementary determining region (HC-CDR) 1 comprising GYFIN (SEQ ID NO: 1); HC-CDR2 comprising RIYPYNVX1TFYNQNFKG (SEQ ID NO: 45), wherein X1 is D or N; and HC-CDR3 comprising GTHYYGSSGAMDY (SEQ ID NO: 16); and a light chain variable domain ( VL ), the VL comprising: a light chain complementary determining region (LC-CDR) 1 comprising KASQNVGTAVA (SEQ ID NO: 23); LC-CDR2 comprising SASNRYT (SEQ ID NO: 30); and LC-CDR3 comprising QQYSSYPYT (SEQ ID NO: 37).
  • VH heavy chain variable domain
  • HC-CDR heavy chain complementary determining region
  • HC-CDR2 comprising RIYPYNVX1TFY
  • the present application provides an anti-LIGHT antibody, the anti-LIGHT antibody comprising: a heavy chain variable domain ( VH ), the VH comprising: a heavy chain complementary determining region (HC-CDR) 1, which comprises GYFMN (SEQ ID NO: 2); HC-CDR2, which comprising RIYPYSGDTFYNQKFNN (SEQ ID NO: 10); and HC-CDR3 comprising SEHFGRNYGTGAVDY (SEQ ID NO: 17); and a light chain variable domain ( VL ), wherein the VL comprises: a light chain complementarity determining region (LC-CDR) 1 comprising RSSQGLVHSNGNTYLH (SEQ ID NO: 24); a LC-CDR2 comprising KVSNRFS (SEQ ID NO: 31); and a LC-CDR3 comprising SQSTHVPYT (SEQ ID NO: 38).
  • VH heavy chain variable domain
  • HC-CDR heavy chain complementary determining region
  • HC-CDR
  • the present application provides an anti-LIGHT antibody, comprising: a heavy chain variable domain (V H ), the V H comprising: a heavy chain complementary determining region (HC-CDR) 1 comprising GYFMN (SEQ ID NO: 2); HC-CDR2 comprising RIYPYSGDTFYNQKFNN (SEQ ID NO: 10); and HC-CDR3 comprising SEHFGRNYGTGAVDY (SEQ ID NO: 17); and a light chain variable domain (V L ), the V L comprising: a light chain complementary determining region (LC-CDR) 1 comprising RSSQSLVHSNGNTYLH (SEQ ID NO: 25); LC-CDR2 comprising KVSNRFS (SEQ ID NO: 31); and LC-CDR3 comprising SQSTHVPLT (SEQ ID NO: 39).
  • V H heavy chain variable domain
  • HC-CDR heavy chain complementary determining region
  • HC-CDR2 comprising RIYPYSGDTFYNQK
  • the present application provides an anti-LIGHT antibody, comprising: a heavy chain variable domain (V H ), the V H comprising: a heavy chain complementarity determining region (HC-CDR) 1 comprising NYYVY (SEQ ID NO: 3); HC-CDR2 comprising EINPTNGDPNFNEKFKS (SEQ ID NO: 11); and HC-CDR3 comprising SNWDYGNAMDF (SEQ ID NO: 18); and a light chain variable domain (V L ), the V L comprising: a light chain complementarity determining region (LC-CDR) 1 comprising KASQSVDFDGDGYMN (SEQ ID NO: 26); LC-CDR2 comprising KASHLDS (SEQ ID NO: 32); and LC-CDR3 comprising QQSIEDPFT (SEQ ID NO: 41).
  • V H heavy chain variable domain
  • HC-CDR heavy chain complementarity determining region
  • HC-CDR2 comprising EINPTNGDPNFNEKFKS (
  • the present application provides an anti-LIGHT antibody, comprising: a heavy chain variable domain (V H ), the V H comprising: a heavy chain complementary determining region (HC-CDR) 1 comprising NYGMN (SEQ ID NO: 4); HC-CDR2 comprising WINTYTGEPTYADDFKG (SEQ ID NO: 12); and HC-CDR3 comprising DNWDGKGMDY (SEQ ID NO: 19); and a light chain variable domain (V L ), the V L comprising: a light chain complementary determining region (LC-CDR) 1 comprising KASQDVDTAVA (SEQ ID NO: 27); LC-CDR2 comprising WASTRHT (SEQ ID NO: 33); and LC-CDR3 comprising HQYGSYPLT (SEQ ID NO: 42).
  • V H heavy chain variable domain
  • HC-CDR heavy chain complementary determining region
  • HC-CDR2 comprising WINTYTGEPTYADDFKG
  • HC-CDR3 comprising DNW
  • the present application provides an anti-LIGHT antibody, comprising: a heavy chain variable domain (V H ), the V H comprising: a heavy chain complementary determining region (HC-CDR) 1 comprising TYYMY (SEQ ID NO: 5); HC-CDR2 comprising EINPTNGGTIFNEKFKT (SEQ ID NO: 13); and HC-CDR3 comprising GNWPYWSFDV (SEQ ID NO: 20); and a light chain variable domain (V L ), the V L comprising: a light chain complementary determining region (LC-CDR) 1 comprising KASQSVDFDGDNYMN (SEQ ID NO: 28); LC-CDR2 comprising AASNLDS (SEQ ID NO: 34); and LC-CDR3 comprising QQSIEDPWT (SEQ ID NO: 43).
  • V H heavy chain variable domain
  • HC-CDR heavy chain complementary determining region
  • HC-CDR2 comprising EINPTNGGTIFNEKFKT
  • the present application provides an anti-LIGHT antibody, comprising: a heavy chain variable domain (V H ), the V H comprising: a heavy chain complementary determining region (HC-CDR) 1 comprising DHIMN (SEQ ID NO: 6); HC-CDR2 comprising RIYPVSGETNYNQKFMG (SEQ ID NO: 14); and HC-CDR3 comprising GSYYWNAMDY (SEQ ID NO: 21); and a light chain variable domain (V L ), the V L comprising: a light chain complementary determining region (LC-CDR) 1 comprising KASQSVDFDGDSYMN (SEQ ID NO: 29) or KASQSVDFDGESYMN (SEQ ID NO: 83); LC-CDR2 comprising SASNLES (SEQ ID NO: 35); and LC-CDR3 comprising QQSIEDPWT (SEQ ID NO: 43).
  • V H heavy chain variable domain
  • HC-CDR heavy chain complementary determining region
  • the present application provides an anti-LIGHT antibody, comprising: a heavy chain variable domain (V H ), the V H comprising: a heavy chain complementary determining region (HC-CDR) 1 comprising SYNVH (SEQ ID NO: 7); HC-CDR2 comprising AVYPGNGDTSYNQKFKG (SEQ ID NO: 15); and HC-CDR3 comprising GSYYYTSSYFDH (SEQ ID NO: 22); and a light chain variable domain (V L ), the V L comprising: a light chain complementary determining region (LC-CDR) 1 comprising KASQSVDFDGDSYMN (SEQ ID NO: 29); LC-CDR2 comprising TASNLES (SEQ ID NO: 36); and LC-CDR3 comprising QQSYEDPFT (SEQ ID NO: 44).
  • V H heavy chain variable domain
  • HC-CDR heavy chain complementary determining region
  • HC-CDR2 comprising AVYPGNGDTSYNQ
  • nucleic acids encoding anti-LIGHT antibodies are also provided.
  • compositions comprising anti-LIGHT antibodies are also provided.
  • treatment is a method of obtaining beneficial or desired results, including clinical results.
  • the beneficial or desired clinical results include, but are not limited to, one or more of the following: alleviating one or more symptoms caused by the disease, reducing the extent of the disease, stabilizing the disease (e.g., preventing or delaying disease progression), preventing or delaying the spread of the disease (e.g., metastasis), preventing or delaying disease recurrence, delaying or slowing disease progression, improving the disease state, alleviating the disease (partially or completely), reducing the dose of one or more other drugs required to treat the disease, delaying disease progression, improving or enhancing quality of life, increasing body weight, and/or prolonging survival.
  • treatment also includes a reduction in the pathological consequences of the disease (e.g., forced expiratory volume for asthma). The methods of the present application take into account any one or more aspects of these treatments.
  • the CDR boundaries of the antibodies or antigen-binding fragments disclosed herein can be defined or identified by the Kabat, Chothia or Al-Lazikani conventions (Al-Lazikani 1997; Chothia 1985; Chothia 1987; Chothia 1989; Kabat 1987; Kabat 1991).
  • the three CDR regions of the heavy or light chain are inserted between flanking segments called framework regions (FRs), which are more highly conserved than the CDR regions and form a scaffold that supports the hypervariable loops.
  • FRs flanking segments
  • the constant regions of the heavy and light chains are not involved in antigen binding but exhibit a variety of effector functions.
  • Antibodies are classified based on the amino acid sequence of their heavy chain constant regions.
  • the five major classes or isotypes of antibodies are IgA, IgD, IgE, IgG, and IgM, which are characterized by their Heavy chains are of type ⁇ , ⁇ , ⁇ , ⁇ , and ⁇ .
  • the major classes of antibodies are divided into subclasses, such as IgG1 ( ⁇ 1 heavy chain), IgG2 ( ⁇ 2 heavy chain), IgG3 ( ⁇ 3 heavy chain), IgG4 ( ⁇ 4 heavy chain), IgA1 ( ⁇ 1 heavy chain), or IgA2 ( ⁇ 2 heavy chain).
  • antigen-binding fragment includes antibody fragments, such as diabodies, Fab, Fab', F(ab') 2 , Fv fragments, disulfide-stabilized Fv fragments (dsFv), (dsFv) 2 , bispecific dsFv (dsFv-dsFv'), disulfide-stabilized diabodies (dsdiabodies), single-chain Fv (scFv), scFv dimers (divalent diabodies), multispecific antibodies composed of antibody fragments comprising one or more CDRs, single-domain antibodies, nanobodies, domain antibodies, bivalent domain antibodies, or any other antibody fragment that can bind to an antigen but does not contain a complete antibody structure.
  • antibody fragments such as diabodies, Fab, Fab', F(ab') 2 , Fv fragments, disulfide-stabilized Fv fragments (dsFv), (dsFv) 2 , bispecific dsFv (dsFv
  • Antigen-binding fragments can bind to the same antigen as a parent antibody or a parent antibody fragment (such as a parent scFv). Antigen-binding fragments also include fusion proteins comprising the above antibody fragments. In some embodiments, an antigen-binding fragment may include one or more CDRs from a specific human antibody, which are grafted to the framework region from one or more different human antibodies.
  • epitope refers to a specific group of atoms or amino acids on an antigen to which an antibody or antibody portion binds. If two antibodies or antibody portions exhibit competitive binding to an antigen, they are likely to bind to the same epitope on the antigen.
  • a first antibody "competes" for binding to a LIGHT target with a second antibody when the first antibody inhibits binding of the second antibody to the LIGHT target by at least 50% (e.g., at least 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, or 99%) at equimolar concentrations, and vice versa.
  • PCT Publication WO 03/48731 describes a high-throughput antibody "epitope binning" method based on cross-competition.
  • the terms “specifically bind”, “specifically recognize” or “specific for” refer to a measurable and reproducible interaction, such as the binding of an antibody to a target that can determine the presence of the target in a heterogeneous population of molecules, including biomolecules.
  • an antibody can specifically recognize a target (which can be an epitope) means that the antibody binds to the target with higher affinity, avidity, more readily and/or more persistently than it binds to other targets.
  • an antibody that specifically recognizes an antigen reacts with one or more antigenic determinants of the antigen with an affinity that is at least 10 times greater than its binding affinity to other targets.
  • an "isolated" anti-LIGHT antibody refers to an anti-LIGHT antibody that (1) is not related to naturally occurring proteins, (2) does not contain other proteins from the same source, (3) is expressed by cells of a different species, or (4) does not exist in nature.
  • isolated nucleic acid refers to a nucleic acid of genomic, cDNA or synthetic origin or a combination thereof. Depending on its origin, the "isolated nucleic acid” means (1) unrelated to all or part of the polynucleotides in the “isolated nucleic acid” found in nature, (2) operably linked to polynucleotides not naturally associated therewith, or (3) not present as part of a longer sequence in nature.
  • CDR complementarity determining region
  • chimeric antibody refers to an antibody in which a portion of the heavy chain and/or light chain is identical or homologous to the corresponding sequence in an antibody from a specific species or belonging to a specific antibody class or subclass, and the remaining portion of the chain(s) is identical or homologous to the corresponding sequence in an antibody from another genus or belonging to another antibody class or subclass, as well as fragments of such antibodies, as long as they have the biological activity described in the present application (see U.S. Patent No. 4,816,567; and Morrison et al., Proc. Natl. Acad. Sci. USA, 81:6851-6855 (1984)).
  • Fv is the smallest antibody fragment that contains a complete antigen recognition and binding site. This fragment is a dimer formed by a heavy chain variable domain and a light chain variable domain tightly non-covalently linked. Six hypervariable loops (3 loops each in the light chain and heavy chain) are derived from the folding of these two domains, which provide the antibody with amino acid residues for binding to the antigen and give the antibody specificity for binding to the antigen. However, even a single variable domain (or half of an Fv fragment, which contains only 3 CDRs specific for the antigen) has the ability to recognize and bind to the antigen, although its affinity is lower than that of the complete binding site.
  • Single-chain Fv also abbreviated as “sFv” or “scFv”
  • sFv is an antibody fragment comprising VH and VL antibody domains connected into a single polypeptide chain.
  • the scFv polypeptide further comprises a connecting polypeptide between the VH and VL domains, which enables the scFv to form an ideal structure for antigen binding.
  • scFv see Pluckthun in The Pharmacology of Monoclonal Antibodies, vol. 113, Rosenburg and Moore eds., Springer-Verlag, New York, pp. 269-315 (1994).
  • diabody is a small antibody fragment prepared by constructing an scFv fragment (see above) using a short linker (e.g., 5 to 10 residues) between the VH and VL domains, so that the variable domains are paired between chains rather than within the chains, resulting in a bivalent fragment, i.e., a fragment with two antigen binding sites.
  • Bispecific diabodies are heterodimers of two "crossed" scFv fragments, in which the VH and VL domains of the two antibodies are located on different polypeptide chains.
  • Diabodies are fully described in EP 404,097; WO 93/11161; Hollinger et al., Proc. Natl. Acad. Sci. USA, 90: 6444-6448 (1993).
  • the "humanized" form of a non-human (such as rodent) antibody is a chimeric antibody that includes minimal sequences from a non-human antibody.
  • a humanized antibody is a human immunoglobulin (receptor antibody) in which the hypervariable region (HVR) residues of the receptor antibody are replaced by residues from a non-human species such as a mouse, rat, rabbit or non-human mammal with an ideal antibody specificity, affinity and performance (donor antibody).
  • residues in the framework region of a human immunoglobulin are replaced by corresponding non-human residues.
  • a humanized antibody may include residues that are not present in either the receptor antibody or the donor antibody. These modifications can further improve the performance of the antibody.
  • a humanized antibody will include substantially all, at least one, and usually two variable domains, wherein all or substantially all of the hypervariable loops correspond to the hypervariable loops of a non-human immunoglobulin, and all or substantially all of the framework regions are human immunoglobulin sequences.
  • Human antibodies optionally also include at least a portion of an immunoglobulin constant region (Fc), typically a constant region of a human immunoglobulin.
  • Fc immunoglobulin constant region
  • the "percent (%) amino acid sequence identity" or “homology” of the polypeptide and antibody sequences identified herein is defined as the percentage of identical amino acid residues in a candidate sequence and the polypeptide sequence to be compared, when conservative substitutions are considered to be part of the sequence identity.
  • the percentage of amino acid sequence identity can be determined by a variety of alignment methods within the skill of the art, for example, using publicly available computer software such as BLAST, BLAST-2, ALIGN, Megalign (DNASTAR), or MUSCLE software.
  • One skilled in the art can determine appropriate parameters for measuring alignment, including any algorithm required to maximize alignment over the full length of the sequences being compared.
  • Fc receptor or "FcR” is used to describe a receptor that binds to the Fc region of an antibody.
  • the FcR described herein is an FcR that binds to an IgG antibody (a gamma receptor), including receptors of the Fc ⁇ RI, Fc ⁇ RII, and Fc ⁇ RIII subclasses, including allelic variants and alternatively spliced forms of these receptors.
  • Fc ⁇ RII receptors include Fc ⁇ RIIA ("activating receptor") and Fc ⁇ RIIB ("inhibiting receptor”), which have similar amino acid sequences and differ primarily in the cytoplasmic domain.
  • the cytoplasmic domain of the activating receptor Fc ⁇ RIIA contains an immunoreceptor tyrosine-based activation motif (ITAM).
  • the cytoplasmic domain of the inhibitory receptor Fc ⁇ RIIB contains an immunoreceptor tyrosine-based inhibition motif (ITIM) (see M.in Annu. Rev. Immunol. 15: 203-234 (1997). Allotypes are also included, such as the Fc ⁇ RIIIA allotypes: Fc ⁇ RIIIA-Phe158, Fc ⁇ RIIIA-Val158, Fc ⁇ RIIA-R131 and/or Fc ⁇ RIIA-H131. FcRs are described in Ravetch and Kinet, Annu. Rev.
  • FcR in this application encompasses other types of FcRs, including FcRs identified in the future.
  • FcR also includes the neonatal receptor FcRn, which is responsible for the transfer of maternal IgGs to the newborn (Guyer et al., J. Immunol. 117:587 (1976) and Kim et al., J. Immunol. 24:249 (1994)).
  • FcRn refers to the neonatal Fc receptor (FcRn).
  • FcRn is structurally similar to the major histocompatibility complex (MHC) and consists of an ⁇ chain non-covalently bound to ⁇ 2 microglobulin.
  • MHC major histocompatibility complex
  • FcRn plays an important role in the passive transport of immunoglobulins IgGs from mother to newborn and in regulating serum IgG levels.
  • FcRn acts as a salvage receptor that binds and transports endocytosed IgG in an intact form within and between cells and protects them from the default degradation pathway.
  • the "CH1 domain" of a human IgG heavy chain constant region typically stretches from amino acid 118 to amino acid 215 (EU numbering system).
  • the "hinge region” is generally defined as extending from Glu 216 to Pro 230 of human IgG1 (Burton, Molec. Immunol. 22: 161-206 (1985)). By placing the first and last cysteine residues that form inter-heavy chain disulfide bonds in the same position as IgG1, the hinge regions of other IgG isotypes can be aligned with the IgG1 sequence.
  • the "CH2 domain" of the human IgG Fc region typically extends from amino acid 231 to amino acid 340.
  • the CH2 domain is unique in that it does not pair closely with another region, but rather two N-terminally linked branched sugar chains are inserted between the two CH2 domains of the intact native IgG molecule. It is speculated that carbohydrates may serve as a substitute for domain-to-domain pairing, helping to maintain CH2 domain stability. Burton, Molec. Immunol. 22: 161-206 (1985).
  • the "CH3" domain includes the stretch from the C-terminal residue to the CH2 domain within the Fc region (from amino acid 341 to the C-terminus of the antibody sequence, generally amino acid residue 446 or 447 for IgG).
  • a “functional Fc fragment” has the "effector functions" possessed by a native Fc region sequence.
  • exemplary “effector functions” include C1q binding; complement-dependent cytotoxicity (CDC); Fc receptor binding; antibody-dependent cell-mediated cytotoxicity (ADCC); phagocytosis; downregulation of cell surface receptors (such as B cell receptor; BCR), etc.
  • Such effector functions generally require the Fc region to be combined with a binding domain (such as an antibody variable region) and can be evaluated using a variety of experimental methods known in the art.
  • Antibodies with IgG Fc variants having "altered" FcR binding affinity or ADCC activity have enhanced or diminished FcR binding activity and/or ADCC activity compared to the parent polypeptide or a polypeptide comprising a native Fc sequence.
  • Fc variants that exhibit "enhanced binding" to FcR have a higher binding affinity (e.g., a lower apparent Kd or IC 50 value) to at least one FcR compared to the parent polypeptide or a polypeptide comprising a native IgG Fc sequence.
  • the binding ability is enhanced by 3 times, e.g., 5, 10, 25, 50, 60, 100, 150, 200, or even up to 500 times, or the binding ability is increased by 25% to 1000%, compared to the parent polypeptide.
  • Fc variants that exhibit "reduced binding" to FcR have a lower affinity (e.g., a higher apparent Kd or IC 50 value) to at least one FcR compared to the parent polypeptide.
  • the binding ability is decreased by 40% or more compared to the parent polypeptide.
  • ADCC antibody-dependent cell-mediated cytotoxicity
  • FcRs Fc receptors
  • cytotoxic cells e.g., natural killer (NK) cells, neutrophils, and macrophages
  • NK cells e.g., natural killer (NK) cells, neutrophils, and macrophages
  • Antibodies "arm” the cytotoxic cells and are required for this killing.
  • NK cells express only Fc ⁇ RIII, while monocytes express Fc ⁇ RI, Fc ⁇ RII, and Fc ⁇ RIII.
  • FcR expression on hematopoietic cells is summarized in Table 3 on page 464 of Ravetch and Kinet, Annu. Rev. Immunol 9:457-92 (1991).
  • an in vitro ADCC assay can be performed, as described in U.S. Patent Nos. 5,500,362 or 5,821,337. Effector cells suitable for such experiments include peripheral blood mononuclear cells (PBMC) and natural killer cells (NK).
  • PBMC peripheral blood mononuclear cells
  • NK natural killer cells
  • ADCC activity of the target molecule can also be assessed in vivo, for example, as described in an animal model disclosed in Clynes et al. PNAS (USA) 95: 652-656 (1998).
  • a polypeptide comprising an Fc region variant exhibits "enhanced ADCC activity" or is capable of more effectively mediating an ADCC effect in the presence of human effector cells compared to a polypeptide comprising a wild-type IgG Fc polypeptide or a parent polypeptide, and the polypeptide comprising an Fc region variant is capable of more effectively mediating ADCC both in vitro and in vivo when the amount of the polypeptide comprising the wild-type IgG Fc polypeptide (or parent polypeptide) is substantially the same during the experiment.
  • Such variants are generally identified using any in vitro ADCC experimental method known in the art, such as an experiment or method for identifying ADCC activity, such as in an animal model, etc. In some embodiments, such variants mediate ADCC 5 to 100 times more efficiently, such as 25 to 50 times, compared to wild-type Fc (or parent polypeptide).
  • “Complement-dependent cytotoxicity” or “CDC” refers to the lysis of target cells in the presence of complement. Activation of the classical complement pathway is initiated by the binding of the first component of the complement system (C1q) to an antibody (of the appropriate structural subclass) that binds to a cognate antigen.
  • C1q the first component of the complement system
  • an antibody of the appropriate structural subclass
  • a CDC assay may be performed, such as that described in Gazzano-Santoro et al., J. Immunol. Methods 202:163 (1996).
  • Polypeptide variants having altered Fc region amino acid sequences and increased or decreased C1q binding ability are described in U.S. Patent No. 6,194,551B1 and WO99/51642. The contents of these patent publications are expressly incorporated herein by reference. See also Idusogie et al. J. Immunol. 164:4178-4184 (2000).
  • nucleotide sequence encoding an amino acid sequence includes all nucleotide sequences that are degenerate forms of each other and encode the same amino acid sequence.
  • a nucleotide sequence encoding a protein or RNA may also include introns, for example, a nucleotide sequence encoding a protein contains introns in some forms.
  • operably linked refers to a functional connection between a regulatory sequence and a heterologous nucleotide sequence, thereby allowing the latter to be expressed.
  • a first nucleotide sequence is operably linked to a second nucleotide sequence when the first nucleotide sequence is in a functional relationship with the second nucleotide sequence.
  • a promoter affects the transcription or expression of a coding sequence
  • the promoter is operably linked to a coding sequence.
  • operably linked DNA sequences are contiguous and, if necessary, two protein coding regions can be linked in the same reading frame.
  • homologous refers to the sequence similarity or sequence identity between two polypeptides or between two nucleic acid molecules. If the same position in two compared sequences is the same base or amino acid monomer subunit, for example, the same position in two DNA molecules is adenine, then the two DNA molecules are homologous at that position.
  • the homology percentage between two sequences refers to the ratio of the number of matching or homologous positions in the two sequences to the total number of positions multiplied by 100. For example, if 6 out of 10 positions in two sequences are If the sequences are matched or homologous, then the homology between the two sequences is 60%. For example, the DNA sequences ATTGCC and TATGGC have 50% homology. Generally speaking, when comparing two sequences, the comparison is performed with the goal of obtaining the maximum homology.
  • an “effective amount” of an anti-LIGHT antibody or composition disclosed herein refers to an amount sufficient to achieve a specific purpose.
  • An “effective amount” can be determined empirically and by known methods related to the purpose.
  • terapéuticaally effective amount refers to the amount of the anti-LIGHT antibody or its composition disclosed herein that can effectively treat a disease or symptom of an individual.
  • “asthma-related parameters” are used as indicators for evaluating the therapeutic effect of asthma, for example, “asthma-related parameters” include: (a) forced expiratory volume in 1 second (FEV1); (b) peak expiratory flow (PEF), including morning PEF (AM PEF) and evening PEF (PM PEF); (c) use of inhaled bronchodilators, such as albuterol or levosalbutamol; (d) five-item Asthma Control Questionnaire (ACQ5) score; (d) nighttime awakening; and (e) 22-item Sino-Nasal Outcome Test (SNOT-22) score.
  • FEV1 forced expiratory volume in 1 second
  • PEF peak expiratory flow
  • AM PEF morning PEF
  • PM PEF evening PEF
  • inhaled bronchodilators such
  • the therapeutically effective amount of an anti-LIGHT antibody or composition disclosed herein can increase one or more of FEV1, AMPEF or PMPEF from baseline, and/or reduce one or more of daily albuterol/levosalbutamol usage, ACQ5 score, average number of awakenings at night, or SNOT-22 score from baseline.
  • baseline refers to the value of an asthma-related parameter of a patient before or at the time of taking the pharmaceutical composition of the present invention.
  • an improvement in an asthma-related parameter refers to an increase of at least 0.10L in FEV1 from baseline.
  • an improvement in an asthma-related parameter refers to an increase of at least 10.0L/min in AMPEF from baseline.
  • an improvement in an asthma-related parameter refers to an increase of at least 1.0L/min in PMPEF from baseline. In some embodiments, an improvement in an asthma-related parameter refers to a reduction of at least 1 puff(s) of albuterol/levosalbutamol usage per day from baseline. In some embodiments, an improvement in an asthma-related parameter refers to a decrease of at least 0.5 points in the ACQ5 score from baseline. In some embodiments, the improvement of asthma-related parameters refers to a decrease in the number of nighttime awakenings from baseline of at least 0.2 times. In some embodiments, the improvement of asthma-related parameters refers to a decrease in the SNOT-22 score of at least 5 points from baseline.
  • the therapeutically effective amount is an amount that can adequately control the disease. In some embodiments, the therapeutically effective amount is an amount that prolongs the patient's survival. In certain embodiments, the therapeutically effective amount is an amount that improves the patient's progression-free survival.
  • pharmaceutically acceptable or “pharmacologically compatible” refers to materials that are free of biological activity or other undesirable properties, such as materials that can be added to a pharmaceutical composition administered to a patient without causing significant adverse biological reactions, or that do not interact in a harmful manner with any other components contained in the composition.
  • Pharmaceutically acceptable carriers or excipients preferably meet the required standards for toxicology or manufacturing testing and/or are included in the inactive ingredient guide compiled by the U.S. Food and Drug Administration.
  • reference to "not" a value or parameter generally indicates and describes "other than” a value or parameter.
  • the method cannot be used to treat type X cancer, meaning that the method is generally used to treat other types of cancer except type X cancer.
  • the present application provides anti-human and/or cynomolgus monkey LIGHT antibodies that specifically bind to LIGHT.
  • the anti-LIGHT antibodies include, but are not limited to, humanized antibodies, chimeric antibodies, mouse antibodies, human antibodies, and antibody molecules comprising heavy chain and/or light chain CDRs as described herein.
  • the present application provides antibodies separated from LIGHT.
  • Anti-LIGHT antibodies contemplated include, for example, full-length anti-LIGHT antibodies (such as full-length IgG1 or IgG4), anti-LIGHT single-chain antibodies, anti-LIGHT Fc fusion proteins, multispecific (such as bispecific) anti-LIGHT antibodies, anti-LIGHT immunoconjugates, and the like.
  • the anti-LIGHT antibody is a full-length antibody (such as full-length IgG1 or IgG4) or an antigen-binding fragment thereof that specifically binds to LIGHT.
  • the anti-LIGHT antibody is Fab, Fab', F(ab)' 2 , Fab'-SH, single-chain Fv (scFv), Fv fragment, dAb, Fd, nanobody, double-chain antibody (diabody) or linear antibody.
  • an antibody that specifically binds to LIGHT refers to an antibody that binds to LIGHT with an affinity that is at least 10 times greater than the affinity for binding to a non-target (including, for example, 10, 10 2 , 10 3 , 10 4 , 10 5 , 10 6 , or 10 7 times).
  • a non-target refers to an antigen that is not LIGHT.
  • Binding affinity can be determined by methods known in the art, such as ELISA, fluorescence activated cell sorting (FACS) analysis, or radioimmunoprecipitation analysis (RIA).
  • Kd values can be determined by methods known in the art, such as surface plasmon resonance (SPR) technology or biolayer interferometry (BLI).
  • non-human anti-LIGHT antibodies comprising human sequences (e.g., human heavy and light chain variable domains comprising human CDR sequences) are discussed extensively herein, non-human anti-LIGHT antibodies are also contemplated.
  • non-human anti-LIGHT antibodies include human CDR sequences and non-human framework sequences of anti-LIGHT antibodies described herein.
  • non-human framework sequences include any sequence for generating heavy and/or light chain variable domains using one or more human CDR sequences as described herein, including, for example, mammals, such as mice, rats, rabbits, pigs, cattle (e.g., cattle, bulls, buffaloes), deer, sheep, goats, chickens, cats, dogs, ferrets, primates (e.g., small apes, macaques), etc.
  • non-human anti-LIGHT antibodies include anti-LIGHT antibodies generated by transplanting one or more human CDR sequences described herein into non-human framework regions (e.g., mouse or chicken framework region sequences).
  • amino acid sequence of an exemplary human LIGHT comprises or consists of the amino acid sequence shown in SEQ ID NO: 78.
  • the anti-LIGHT antibodies described herein specifically recognize epitopes in human LIGHT. In some embodiments, the anti-LIGHT antibodies cross-react with LIGHT of species other than humans. In some embodiments, the anti-LIGHT antibodies are completely specific to human LIGHT and do not cross-react with other non-human species.
  • the anti-LIGHT antibody cross-reacts with at least one allelic variant of a LIGHT protein (or a fragment thereof).
  • the allelic variant has up to 30 (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, or 30) amino acid substitutions (e.g., conservative substitutions) compared to a naturally occurring LIGHT protein (or a fragment thereof).
  • the anti-LIGHT antibody does not cross-react with any allelic variant of the LIGHT protein (or a fragment thereof).
  • the anti-LIGHT antibody cross-reacts with at least one interspecies variant of the LIGHT protein.
  • the LIGHT protein (or its fragment) is human LIGHT
  • the interspecies variant of the LIGHT protein (or its fragment) is a variant in cynomolgus monkeys.
  • the anti-LIGHT antibody does not cross-react with any interspecies variant of the LIGHT protein.
  • the anti-LIGHT antibody comprises an antibody heavy chain constant region and an antibody light chain constant region.
  • the anti-LIGHT antibody comprises an IgG1-type heavy chain constant region.
  • the anti-LIGHT antibody comprises an IgG2-type heavy chain constant region.
  • the anti-LIGHT antibody comprises an IgG3-type heavy chain constant region.
  • the anti-LIGHT antibody comprises an IgG4-type heavy chain constant region.
  • the heavy chain constant region comprises (including consisting of or consisting essentially of) the amino acid sequence SEQ ID NO:74.
  • the heavy chain constant region comprises (including consisting of or consisting essentially of) the amino acid sequence SEQ ID NO:75.
  • the anti-LIGHT antibody comprises a kappa light chain constant region.
  • the light chain constant region comprises (including consisting of or consisting essentially of) the amino acid sequence SEQ ID NO:76.
  • the anti-LIGHT antibody comprises a lambda light chain constant region.
  • the light chain constant region comprises (including consisting of or consisting essentially of) the amino acid sequence SEQ ID NO:77.
  • the anti-LIGHT antibody comprises an antibody heavy chain variable domain and an antibody light chain variable domain.
  • the anti-LIGHT antibody comprises a heavy chain variable domain ( VH ), the VH comprising: a heavy chain complementary determining region (HC-CDR) 1 comprising GYFIN (SEQ ID NO: 1); HC-CDR2 comprising RIYPYNVX1TFYNQNFKG (SEQ ID NO: 45), wherein X1 is D or N; and HC-CDR3 comprising GTHYYGSSGAMDY (SEQ ID NO: 16); and a light chain variable domain ( VL ), the VL comprising: a light chain complementary determining region (LC-CDR) 1 comprising KASQNVGTAVA (SEQ ID NO: 23); LC-CDR2 comprising SASNRYT (SEQ ID NO: 30); and LC-CDR3 comprising QQYSSYPYT (SEQ ID NO: 37).
  • VH heavy chain variable domain
  • HC-CDR heavy chain complementary determining region
  • HC-CDR2 comprising RIYPYNVX1TFYNQ
  • the anti-LIGHT antibody comprises a VH comprising: HC-CDR1 comprising the amino acid sequence shown in SEQ ID NO: 1 or a variant thereof, wherein the variant comprises substitutions of up to about 3 (eg, 1, 2, or 3) amino acids; HC-CDR2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 8-9 or a variant thereof, wherein the variant comprises substitutions of up to about 3 (eg, 1, 2, or 3) amino acids; and HC-CDR3 comprising the amino acid sequence shown in SEQ ID NO: 16 or a variant thereof, wherein the variant comprises substitutions of up to about 3 (eg, 1, 2, or 3) amino acids.
  • the anti-LIGHT antibody comprises a VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence of any one of SEQ ID NOs:8-9, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO:16.
  • the anti-LIGHT antibody comprises a VL , wherein the VL comprises: an LC-CDR1 comprising the amino acid sequence shown in SEQ ID NO: 23 or a variant thereof, wherein the variant comprises a substitution of up to about 3 (e.g., 1, 2, or 3) amino acids; an LC-CDR2 comprising the amino acid sequence shown in SEQ ID NO: 30 or a variant thereof, wherein the variant comprises a substitution of up to about 3 (e.g., 1, 2 or 3) amino acid substitutions; and LC-CDR3, which comprises the amino acid sequence shown in SEQ ID NO: 37 or a variant thereof, wherein the variant comprises a substitution of up to about 3 (e.g., 1, 2 or 3) amino acids.
  • the VL comprises: an LC-CDR1 comprising the amino acid sequence shown in SEQ ID NO: 23 or a variant thereof, wherein the variant comprises a substitution of up to about 3 (e.g., 1, 2, or 3) amino acids; an LC-CDR2 comprising
  • the anti-LIGHT antibody comprises a VL comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO:23, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO:30, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO:37.
  • the anti-LIGHT antibody comprises a VH comprising: an HC-CDR1 comprising the amino acid sequence shown in SEQ ID NO: 1 or a variant thereof, wherein the variant comprises a substitution of up to about 3 (e.g., 1, 2, or 3) amino acids; an HC-CDR2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 8-9 or a variant thereof, wherein the variant comprises a substitution of up to about 3 (e.g., 1, 2, or 3) amino acids; and an HC-CDR3 comprising the amino acid sequence shown in SEQ ID NO: 16 or a variant thereof, wherein the variant comprises a substitution of up to about 3 (e.g., 1, 2, or 3) amino acids; and a VL comprising: an LC-CDR1 comprising the amino acid sequence shown in SEQ ID NO: 23 or a variant thereof, wherein the variant comprises a substitution of up to about 3 (e.g., 1, 2, or 3) amino acids; an LC-CDR
  • the anti-LIGHT antibody comprises a VH comprising: a HC-CDR1 comprising the amino acid sequence shown in SEQ ID NO: 1, a HC-CDR2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 8-9, and a HC-CDR3 comprising the amino acid sequence shown in SEQ ID NO: 16; and a VL comprising: a LC-CDR1 comprising the amino acid sequence shown in SEQ ID NO: 23, a LC-CDR2 comprising the amino acid sequence shown in SEQ ID NO: 30, and a LC-CDR3 comprising the amino acid sequence shown in SEQ ID NO: 37.
  • the anti-LIGHT antibody comprises a VH comprising: a HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, a HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 8, a HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 16, or a variant of the VH comprising up to about 5 amino acid substitutions in its HC-CDRs; and a VL comprising: a LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 23, a LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 30, a LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 37, or a variant of the VL comprising up to about 5 amino acid substitutions in its LC-CDRs.
  • the anti-LIGHT antibody comprises a VH comprising: a HC-CDR1 comprising the amino acid sequence of SEQ ID NO:1, a HC-CDR2 comprising the amino acid sequence of SEQ ID NO:8, and a HC-CDR3 comprising the amino acid sequence of SEQ ID NO:16; and a VL comprising: a LC-CDR1 comprising the amino acid sequence of SEQ ID NO:23, a LC-CDR2 comprising the amino acid sequence of SEQ ID NO:30, and a LC-CDR3 comprising the amino acid sequence of SEQ ID NO:37.
  • the anti-LIGHT antibody comprises a VH comprising: a HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, a HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 9, a HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 16, or a variant of the VH comprising up to about 5 amino acid substitutions in the HC-CDRs; and a VL comprising: a LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 23, a LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 24. NO:30, LC-CDR3, which comprises the amino acid sequence of SEQ ID NO:37, or a variant of said V L , which comprises substitutions of up to about 5 amino acids in its LC-CDRs.
  • the anti-LIGHT antibody comprises a VH comprising: a HC-CDR1 comprising the amino acid sequence of SEQ ID NO:1, a HC-CDR2 comprising the amino acid sequence of SEQ ID NO:9, and a HC-CDR3 comprising the amino acid sequence of SEQ ID NO:16; and a VL comprising: a LC-CDR1 comprising the amino acid sequence of SEQ ID NO:23, a LC-CDR2 comprising the amino acid sequence of SEQ ID NO:30, and a LC-CDR3 comprising the amino acid sequence of SEQ ID NO:37.
  • the anti-LIGHT antibody comprises a VH comprising HC-CDR1, HC-CDR2 and HC-CDR3 comprised by a VH as shown in any one of the amino acid sequences shown in SEQ ID NOs:46-53; and a VL comprising LC-CDR1, LC-CDR2 and LC-CDR3 comprised by a VL as shown in any one of the amino acid sequences shown in SEQ ID NOs:62-65.
  • the anti-LIGHT antibody comprises a VH comprising HC-CDR1, HC-CDR2 and HC-CDR3 comprised by VH as shown in the amino acid sequence of SEQ ID NO:46; and a VL comprising LC-CDR1, LC-CDR2 and LC-CDR3 comprised by VL as shown in the amino acid sequence of SEQ ID NO:62.
  • the anti-LIGHT antibody comprises a VH comprising HC-CDR1, HC-CDR2 and HC-CDR3 comprised by VH as shown in the amino acid sequence of SEQ ID NO:47; and a VL comprising LC-CDR1, LC-CDR2 and LC-CDR3 comprised by VL as shown in the amino acid sequence of SEQ ID NO:63.
  • the anti-LIGHT antibody comprises a VH comprising HC-CDR1, HC-CDR2 and HC-CDR3 comprised by VH as shown in the amino acid sequence of SEQ ID NO:48; and a VL comprising LC-CDR1, LC-CDR2 and LC-CDR3 comprised by VL as shown in the amino acid sequence of SEQ ID NO:63.
  • the anti-LIGHT antibody comprises a VH comprising HC-CDR1, HC-CDR2 and HC-CDR3 comprised by VH as shown in the amino acid sequence of SEQ ID NO:49; and a VL comprising LC-CDR1, LC-CDR2 and LC-CDR3 comprised by VL as shown in the amino acid sequence of SEQ ID NO:63.
  • the anti-LIGHT antibody comprises a VH comprising HC-CDR1, HC-CDR2 and HC-CDR3 comprised by VH as shown in the amino acid sequence of SEQ ID NO:50; and a VL comprising LC-CDR1, LC-CDR2 and LC-CDR3 comprised by VL as shown in the amino acid sequence of SEQ ID NO:63.
  • the anti-LIGHT antibody comprises a VH comprising HC-CDR1, HC-CDR2 and HC-CDR3 comprised by VH as shown in the amino acid sequence of SEQ ID NO:47; and a VL comprising LC-CDR1, LC-CDR2 and LC-CDR3 comprised by VL as shown in the amino acid sequence of SEQ ID NO:64.
  • the anti-LIGHT antibody comprises a VH comprising HC-CDR1, HC-CDR2 and HC-CDR3 comprised by VH as shown in the amino acid sequence of SEQ ID NO:48; and a VL comprising LC-CDR1, LC-CDR2 and LC-CDR3 comprised by VL as shown in the amino acid sequence of SEQ ID NO:64.
  • the anti-LIGHT antibody comprises a VH comprising HC-CDR1, HC-CDR2 and HC-CDR3 comprised by VH as shown in the amino acid sequence of SEQ ID NO:49; and a VL comprising LC-CDR1, LC-CDR2 and LC-CDR3 comprised by VL as shown in the amino acid sequence of SEQ ID NO:64.
  • the anti-LIGHT antibody comprises a VH comprising HC-CDR1, HC-CDR2 and HC-CDR3 comprised by VH as shown in the amino acid sequence of SEQ ID NO:50; and a VL comprising LC-CDR1, LC-CDR2 and LC-CDR3 comprised by VL as shown in the amino acid sequence of SEQ ID NO:64.
  • the anti-LIGHT antibody comprises a VH comprising HC-CDR1, HC-CDR2 and HC-CDR3 comprised by VH as shown in the amino acid sequence of SEQ ID NO:47; and a VL comprising LC-CDR1, LC-CDR2 and LC-CDR3 comprised by VL as shown in the amino acid sequence of SEQ ID NO:65.
  • the anti-LIGHT antibody comprises a VH comprising HC-CDR1, HC-CDR2 and HC-CDR3 comprised by VH as shown in the amino acid sequence of SEQ ID NO:48; and a VL comprising LC-CDR1, LC-CDR2 and LC-CDR3 comprised by VL as shown in the amino acid sequence of SEQ ID NO:65.
  • the anti-LIGHT antibody comprises a VH comprising HC-CDR1, HC-CDR2 and HC-CDR3 comprised by VH as shown in the amino acid sequence of SEQ ID NO:49; and a VL comprising LC-CDR1, LC-CDR2 and LC-CDR3 comprised by VL as shown in the amino acid sequence of SEQ ID NO:65.
  • the anti-LIGHT antibody comprises a VH comprising HC-CDR1, HC-CDR2 and HC-CDR3 comprised by VH as shown in the amino acid sequence of SEQ ID NO:50; and a VL comprising LC-CDR1, LC-CDR2 and LC-CDR3 comprised by VL as shown in the amino acid sequence of SEQ ID NO:65.
  • the anti-LIGHT antibody comprises a VH comprising HC-CDR1, HC-CDR2 and HC-CDR3 comprised by VH as shown in the amino acid sequence of SEQ ID NO:51; and a VL comprising LC-CDR1, LC-CDR2 and LC-CDR3 comprised by VL as shown in the amino acid sequence of SEQ ID NO:63.
  • the anti-LIGHT antibody comprises a VH comprising HC-CDR1, HC-CDR2 and HC-CDR3 comprised by VH as shown in the amino acid sequence of SEQ ID NO:52; and a VL comprising LC-CDR1, LC-CDR2 and LC-CDR3 comprised by VL as shown in the amino acid sequence of SEQ ID NO:65.
  • the anti-LIGHT antibody comprises a VH comprising HC-CDR1, HC-CDR2 and HC-CDR3 comprised by VH as shown in the amino acid sequence of SEQ ID NO:53; and a VL comprising LC-CDR1, LC-CDR2 and LC-CDR3 comprised by VL as shown in the amino acid sequence of SEQ ID NO:65.
  • the anti-LIGHT antibody comprises a VH comprising HC-CDR1, HC-CDR2 and HC-CDR3 comprised by VH as shown in the amino acid sequence of SEQ ID NO:51; and a VL comprising LC-CDR1, LC-CDR2 and LC-CDR3 comprised by VL as shown in the amino acid sequence of SEQ ID NO:65.
  • the anti-LIGHT antibody comprises: a VH comprising an amino acid sequence as set forth in any one of SEQ ID NOs:46-53 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to an amino acid sequence as set forth in any one of SEQ ID NOs:46-53; and a VL comprising an amino acid sequence as set forth in any one of SEQ ID NOs:62-65 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to an amino acid sequence as set forth in any one of SEQ ID NOs:62-65.
  • the anti-LIGHT antibody comprises a VH comprising an amino acid sequence as set forth in any one of SEQ ID NOs: 46-53 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% ) sequence identity to an amino acid sequence as set forth in any one of SEQ ID NOs:62-65.
  • the amino acid sequence shown in any one of SEQ ID NOs: 53, and V L wherein the V L comprises the amino acid sequence shown in any one of SEQ ID NOs: 62-65.
  • the anti-LIGHT antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 46, or a variant thereof, the variant having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 46; and a VL comprising the amino acid sequence of SEQ ID NO: 62, or a variant thereof, the variant having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 62.
  • the anti-LIGHT antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 46, and a VL comprising the amino acid sequence of SEQ ID NO: 62.
  • the anti-LIGHT antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 47, or a variant thereof, which has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 47; and a VL comprising the amino acid sequence of SEQ ID NO: 63, or a variant thereof, which has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 63.
  • the anti-LIGHT antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 47, and a VL comprising the amino acid sequence of SEQ ID NO: 63.
  • the anti-LIGHT antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 48, or a variant thereof, which has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 48; and a VL comprising the amino acid sequence of SEQ ID NO: 63, or a variant thereof, which has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 63.
  • the anti-LIGHT antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 48, and a VL comprising the amino acid sequence of SEQ ID NO: 63.
  • the anti-LIGHT antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 49, or a variant thereof, which has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 49; and a VL comprising the amino acid sequence of SEQ ID NO: 63, or a variant thereof, which has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 63.
  • the anti-LIGHT antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 49, and a VL comprising the amino acid sequence of SEQ ID NO: 63.
  • the anti-LIGHT antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 50, or a variant thereof, which has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 50; and a VL comprising the amino acid sequence of SEQ ID NO: 63, or a variant thereof, which has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 63.
  • the anti-LIGHT antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 50, and a VL comprising the amino acid sequence of SEQ ID NO: 63.
  • the anti-LIGHT antibody comprises: a VH comprising the amino acid sequence of SEQ ID NO: 47 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, and a VL comprising the amino acid sequence of SEQ ID NO: 64 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99 % ) sequence identity to the amino acid sequence of SEQ ID NO: 64.
  • the anti-LIGHT antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 47, and a VL comprising the amino acid sequence of SEQ ID NO: 64.
  • the anti-LIGHT antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 48, or a variant thereof, which has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 48; and a VL comprising the amino acid sequence of SEQ ID NO: 64, or a variant thereof, which has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 64.
  • the anti-LIGHT antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 48, and a VL comprising the amino acid sequence of SEQ ID NO: 64.
  • the anti-LIGHT antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 49, or a variant thereof, the variant having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 49; and a VL comprising the amino acid sequence of SEQ ID NO: 64, or a variant thereof, the variant having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 64.
  • the anti-LIGHT antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 49, and a VL comprising the amino acid sequence of SEQ ID NO: 64.
  • the anti-LIGHT antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 50, or a variant thereof, which has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 50; and a VL comprising the amino acid sequence of SEQ ID NO: 64, or a variant thereof, which has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 64.
  • the anti-LIGHT antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 50, and a VL comprising the amino acid sequence of SEQ ID NO: 64.
  • the anti-LIGHT antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 47, or a variant thereof, the variant having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 47; and a VL comprising the amino acid sequence of SEQ ID NO: 65, or a variant thereof, the variant having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 65.
  • the anti-LIGHT antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 47, and a VL comprising the amino acid sequence of SEQ ID NO: 65.
  • the anti-LIGHT antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 48, or a variant thereof, which has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 48; and a VL comprising the amino acid sequence of SEQ ID NO: 65, or a variant thereof, which has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 65.
  • the anti-LIGHT antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 48, and a VL comprising the amino acid sequence of SEQ ID NO: 65.
  • the anti-LIGHT antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 49, or a variant thereof, the variant having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 49; and a VL comprising the amino acid sequence of SEQ ID NO: 65, or a variant thereof, the variant having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 65.
  • the anti-LIGHT antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 49, and a VL comprising the amino acid sequence of SEQ ID NO: 65.
  • the anti-LIGHT antibody comprises a VH comprising the amino acid sequence of SEQ ID NO:50, or a variant thereof, which has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence of SEQ ID NO:50; and a VL comprising the amino acid sequence of SEQ ID NO:65, or a variant thereof, which has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence of SEQ ID NO:65.
  • the anti-LIGHT antibody comprises a VH comprising the amino acid sequence of SEQ ID NO:50, and a VL comprising the amino acid sequence of SEQ ID NO:65.
  • the anti-LIGHT antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 51, or a variant thereof, which has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 51; and a VL comprising the amino acid sequence of SEQ ID NO: 63, or a variant thereof, which has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 63.
  • the anti-LIGHT antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 51, and a VL comprising the amino acid sequence of SEQ ID NO: 63.
  • the anti-LIGHT antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 52, or a variant thereof, which has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 52; and a VL comprising the amino acid sequence of SEQ ID NO: 65, or a variant thereof, which has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 65.
  • the anti-LIGHT antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 52, and a VL comprising the amino acid sequence of SEQ ID NO: 65.
  • the anti-LIGHT antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 53, or a variant thereof, which has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 53; and a VL comprising the amino acid sequence of SEQ ID NO: 65, or a variant thereof, which has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 65.
  • the anti-LIGHT antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 53, and a VL comprising the amino acid sequence of SEQ ID NO: 65.
  • the anti-LIGHT antibody comprises: a VH comprising the amino acid sequence of SEQ ID NO:51 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence of SEQ ID NO:51; and a VL comprising the amino acid sequence of SEQ ID NO:65 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence of SEQ ID NO:65.
  • the anti-LIGHT antibody comprises a VH comprising the amino acid sequence of SEQ ID NO:51, and a VL comprising the amino acid sequence of SEQ ID NO:65.
  • the anti-LIGHT antibody comprises a VH comprising: a HC-CDR1 comprising the amino acid sequence of SEQ ID NO:2, a HC-CDR2 comprising the amino acid sequence of SEQ ID NO:10, a HC-CDR3 comprising the amino acid sequence of SEQ ID NO:17, or a variant of the VH comprising up to about 5 amino acid substitutions in its HC-CDRs; and a VL comprising: a LC-CDR1 comprising the amino acid sequence of SEQ ID NO:24, a LC-CDR2 comprising the amino acid sequence of SEQ ID NO:31, a LC-CDR3 comprising the amino acid sequence of SEQ ID NO:38, or a variant of the VL comprising up to about 5 amino acid substitutions in its LC-CDRs.
  • the anti-LIGHT antibody comprises a VH comprising: a HC-CDR1 comprising the amino acid sequence of SEQ ID NO:2, a HC-CDR2 comprising the amino acid sequence of SEQ ID NO:10, and a HC-CDR3 comprising the amino acid sequence of SEQ ID NO:17; and a VL comprising: a LC-CDR1 comprising the amino acid sequence of SEQ ID NO:24, a LC-CDR2 comprising the amino acid sequence of SEQ ID NO:31, and a LC-CDR3 comprising the amino acid sequence of SEQ ID NO:38.
  • the anti-LIGHT antibody comprises a VH comprising HC-CDR1, HC-CDR2 and HC-CDR3 comprised by VH as shown in the amino acid sequence of SEQ ID NO:54; and a VL comprising LC-CDR1, LC-CDR2 and LC-CDR3 comprised by VL as shown in the amino acid sequence of SEQ ID NO:66.
  • the anti-LIGHT antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 54, or a variant thereof, which has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 54; and a VL comprising the amino acid sequence of SEQ ID NO: 66, or a variant thereof, which has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 66.
  • the anti-LIGHT antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 54, and a VL comprising the amino acid sequence of SEQ ID NO: 66.
  • the anti-LIGHT antibody comprises a VH comprising: a HC-CDR1 comprising the amino acid sequence of SEQ ID NO:2, a HC-CDR2 comprising the amino acid sequence of SEQ ID NO:10, a HC-CDR3 comprising the amino acid sequence of SEQ ID NO:17, or a variant of the VH comprising up to about 5 amino acid substitutions in its HC-CDRs; and a VL comprising: a LC-CDR1 comprising the amino acid sequence of SEQ ID NO:25, a LC-CDR2 comprising the amino acid sequence of SEQ ID NO:31, a LC-CDR3 comprising the amino acid sequence of SEQ ID NO:39, or a variant of the VL comprising up to about 5 amino acid substitutions in its LC-CDRs.
  • the anti-LIGHT antibody comprises a VH comprising: a HC-CDR1 comprising the amino acid sequence of SEQ ID NO:2, a HC-CDR2 comprising the amino acid sequence of SEQ ID NO:10, and a HC-CDR3 comprising the amino acid sequence of SEQ ID NO:17; and a VL comprising: a LC-CDR1 comprising the amino acid sequence of SEQ ID NO:25, a LC-CDR2 comprising the amino acid sequence of SEQ ID NO:31, and a LC-CDR3 comprising the amino acid sequence of SEQ ID NO:39.
  • the anti-LIGHT antibody comprises a VH comprising HC-CDR1, HC-CDR2 and HC-CDR3 comprised by VH as shown in the amino acid sequence of SEQ ID NO:55; and a VL comprising LC-CDR1, LC-CDR2 and LC-CDR3 comprised by VL as shown in the amino acid sequence of SEQ ID NO:67.
  • the anti-LIGHT antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 55, or a variant thereof, which has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 55; and a VL comprising the amino acid sequence of SEQ ID NO: 67, or a variant thereof, which has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 67.
  • the anti-LIGHT antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 55, and a VL comprising the amino acid sequence of SEQ ID NO: 67.
  • the anti-LIGHT antibody comprises a VH comprising: a HC-CDR1 comprising the amino acid sequence of SEQ ID NO:3, a HC-CDR2 comprising the amino acid sequence of SEQ ID NO:11, a HC-CDR3 comprising the amino acid sequence of SEQ ID NO:18, or a variant of the VH comprising up to about 5 amino acid substitutions in its HC-CDRs; and a VL comprising: a LC-CDR1 comprising the amino acid sequence of SEQ ID NO:26, a LC-CDR2 comprising the amino acid sequence of SEQ ID NO:32, a LC-CDR3 comprising the amino acid sequence of SEQ ID NO:40, or a variant of the VL comprising up to about 5 amino acid substitutions in its LC-CDRs.
  • the anti-LIGHT antibody comprises a VH comprising: a HC-CDR1 comprising the amino acid sequence of SEQ ID NO:3, a HC-CDR2 comprising the amino acid sequence of SEQ ID NO:11, and a HC-CDR3 comprising the amino acid sequence of SEQ ID NO:18; and a VL comprising: a LC-CDR1 comprising the amino acid sequence of SEQ ID NO:26, a LC-CDR2 comprising the amino acid sequence of SEQ ID NO:32, and a LC-CDR3 comprising the amino acid sequence of SEQ ID NO:40.
  • the anti-LIGHT antibody comprises a VH comprising HC-CDR1, HC-CDR2 and HC-CDR3 comprised by VH as shown in the amino acid sequence of SEQ ID NO:56; and a VL comprising LC-CDR1, LC-CDR2 and LC-CDR3 comprised by VL as shown in the amino acid sequence of SEQ ID NO:68.
  • the anti-LIGHT antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 56, or a variant thereof, which has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 56; and a VL comprising the amino acid sequence of SEQ ID NO: 68, or a variant thereof, which has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 68.
  • the anti-LIGHT antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 56, and a VL comprising the amino acid sequence of SEQ ID NO: 68.
  • the anti-LIGHT antibody comprises a VH comprising: a HC-CDR1 comprising the amino acid sequence of SEQ ID NO:3, a HC-CDR2 comprising the amino acid sequence of SEQ ID NO:11, a HC-CDR3 comprising the amino acid sequence of SEQ ID NO:18, or a variant of the VH comprising up to about 5 amino acid substitutions in its HC-CDRs; and a VL comprising: a LC-CDR1 comprising the amino acid sequence of SEQ ID NO:26, a LC-CDR2 comprising the amino acid sequence of SEQ ID NO:32, a LC-CDR3 comprising the amino acid sequence of SEQ ID NO:41, or a variant of the VL comprising up to about 5 amino acid substitutions in its LC-CDRs.
  • the anti-LIGHT antibody comprises a VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO:3, HC-CDR2 comprising the amino acid sequence of SEQ ID NO:11, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:18; and a VL comprising: a LC-CDR1 comprising the amino acid sequence of SEQ ID NO:26, a LC-CDR2 comprising the amino acid sequence of SEQ ID NO:32, and a LC-CDR3 comprising the amino acid sequence of SEQ ID NO:41.
  • the anti-LIGHT antibody comprises a VH comprising HC-CDR1, HC-CDR2 and HC-CDR3 comprised by VH as shown in the amino acid sequence of SEQ ID NO:57; and a VL comprising LC-CDR1, LC-CDR2 and LC-CDR3 comprised by VL as shown in the amino acid sequence of SEQ ID NO:69.
  • the anti-LIGHT antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 57, or a variant thereof, which has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 57; and a VL comprising the amino acid sequence of SEQ ID NO: 69, or a variant thereof, which has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 69.
  • the anti-LIGHT antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 57, and a VL comprising the amino acid sequence of SEQ ID NO: 69.
  • the anti-LIGHT antibody comprises a VH comprising: a HC-CDR1 comprising the amino acid sequence of SEQ ID NO:4, a HC-CDR2 comprising the amino acid sequence of SEQ ID NO:12, a HC-CDR3 comprising the amino acid sequence of SEQ ID NO:19, or a variant of the VH comprising up to about 5 amino acid substitutions in its HC-CDRs; and a VL comprising: a LC-CDR1 comprising the amino acid sequence of SEQ ID NO:27, a LC-CDR2 comprising the amino acid sequence of SEQ ID NO:33, a LC-CDR3 comprising the amino acid sequence of SEQ ID NO:42, or a variant of the VL comprising up to about 5 amino acid substitutions in its LC-CDRs.
  • the anti-LIGHT antibody comprises a VH comprising: a HC-CDR1 comprising the amino acid sequence of SEQ ID NO:4, a HC-CDR2 comprising the amino acid sequence of SEQ ID NO:12, and a HC-CDR3 comprising the amino acid sequence of SEQ ID NO:19; and a VL comprising: a LC-CDR1 comprising the amino acid sequence of SEQ ID NO:27, a LC-CDR2 comprising the amino acid sequence of SEQ ID NO:33, and a LC-CDR3 comprising the amino acid sequence of SEQ ID NO:42.
  • the anti-LIGHT antibody comprises a VH comprising HC-CDR1, HC-CDR2 and HC-CDR3 comprised by VH as shown in the amino acid sequence of SEQ ID NO:58; and a VL comprising LC-CDR1, LC-CDR2 and LC-CDR3 comprised by VL as shown in the amino acid sequence of SEQ ID NO:70.
  • the anti-LIGHT antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 58, or a variant thereof, which has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 58; and a VL comprising the amino acid sequence of SEQ ID NO: 70, or a variant thereof, which has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 70.
  • the anti-LIGHT antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 58, and a VL comprising the amino acid sequence of SEQ ID NO: 70.
  • the anti-LIGHT antibody comprises a VH comprising: a HC-CDR1 comprising the amino acid sequence of SEQ ID NO:5, a HC-CDR2 comprising the amino acid sequence of SEQ ID NO:13, a HC-CDR3 comprising the amino acid sequence of SEQ ID NO:20, or a variant of the VH comprising up to about 5 amino acid substitutions in the HC-CDRs; and a VL comprising: a LC-CDR1 comprising the amino acid sequence of SEQ ID NO:28, a LC-CDR2 comprising the amino acid sequence of SEQ ID NO: NO:34, LC-CDR3, which comprises the amino acid sequence of SEQ ID NO:43, or a variant of said V L , which comprises substitutions of up to about 5 amino acids in its LC-CDRs.
  • the anti-LIGHT antibody comprises a VH comprising: a HC-CDR1 comprising the amino acid sequence of SEQ ID NO:5, a HC-CDR2 comprising the amino acid sequence of SEQ ID NO:13, and a HC-CDR3 comprising the amino acid sequence of SEQ ID NO:20; and a VL comprising: a LC-CDR1 comprising the amino acid sequence of SEQ ID NO:28, a LC-CDR2 comprising the amino acid sequence of SEQ ID NO:34, and a LC-CDR3 comprising the amino acid sequence of SEQ ID NO:43.
  • the anti-LIGHT antibody comprises a VH comprising HC-CDR1, HC-CDR2 and HC-CDR3 comprised by VH as shown in the amino acid sequence of SEQ ID NO:59; and a VL comprising LC-CDR1, LC-CDR2 and LC-CDR3 comprised by VL as shown in the amino acid sequence of SEQ ID NO:71.
  • the anti-LIGHT antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 59, or a variant thereof, which has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 59; and a VL comprising the amino acid sequence of SEQ ID NO: 71, or a variant thereof, which has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 71.
  • the anti-LIGHT antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 59, and a VL comprising the amino acid sequence of SEQ ID NO: 71.
  • an isolated anti-LIGHT antibody comprising a heavy chain variable domain ( VH ), the VH comprising a heavy chain complementary determining region (HC-CDR) 1 comprising DHIMN (SEQ ID NO:6); HC-CDR2 comprising RIYPVSGETNYNQKFMG (SEQ ID NO:14); and HC-CDR3 comprising GSYYWNAMDY (SEQ ID NO:21); and a light chain variable domain ( VL ), the VL comprising: a light chain complementary determining region (LC-CDR) 1 comprising KASQSVDFDGDSYMN (SEQ ID NO:29) or KASQSVDFDGESYMN (SEQ ID NO:83); LC-CDR2 comprising SASNLES (SEQ ID NO:35); and LC-CDR3 comprising QQSIEDPWT (SEQ ID NO:43).
  • VH heavy chain variable domain
  • HC-CDR heavy chain complementary determining region 1 comprising DHIMN (SEQ ID NO
  • the anti-LIGHT antibody comprises a VH comprising: HC-CDR1 comprising the amino acid sequence shown in SEQ ID NO:6 or a variant thereof, wherein the variant comprises substitutions of up to about 3 (eg, 1, 2, or 3) amino acids; HC-CDR2 comprising the amino acid sequence shown in SEQ ID NO:14 or a variant thereof, wherein the variant comprises substitutions of up to about 3 (eg, 1, 2, or 3) amino acids; and HC-CDR3 comprising the amino acid sequence shown in SEQ ID NO:21 or a variant thereof, wherein the variant comprises substitutions of up to about 3 (eg, 1, 2, or 3) amino acids.
  • the anti-LIGHT antibody comprises a VH comprising: a HC-CDR1 comprising the amino acid sequence of SEQ ID NO:6, a HC-CDR2 comprising the amino acid sequence of SEQ ID NO:14, and a HC-CDR3 comprising the amino acid sequence of SEQ ID NO:21.
  • the anti-LIGHT antibody comprises a VL , wherein the VL comprises: an LC-CDR1 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 29 or 83 or a variant thereof, wherein the variant comprises a substitution of at most about 3 (e.g., 1, 2, or 3) amino acids; an LC-CDR2 comprising an amino acid sequence as shown in SEQ ID NO: 35 or a variant thereof, wherein the variant comprises at most about 3 (e.g., 1, 2, or 3) amino acids; A LC-CDR3 comprising the amino acid sequence shown in SEQ ID NO: 43 or a variant thereof, wherein the variant comprises a substitution of up to about 3 (e.g., 1, 2 or 3) amino acids.
  • VL comprises: an LC-CDR1 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 29 or 83 or a variant thereof, wherein the variant comprises a substitution of at most about 3 (e.g., 1, 2, or 3) amino acids
  • the anti-LIGHT antibody comprises a VL comprising: an LC-CDR1 comprising an amino acid sequence as shown in any one of SEQ ID NOs:29 or 83, an LC-CDR2 comprising an amino acid sequence as shown in SEQ ID NO:35, and an LC-CDR3 comprising an amino acid sequence as shown in SEQ ID NO:43.
  • the anti-LIGHT antibody comprises a VH comprising: an HC-CDR1 comprising an amino acid sequence as set forth in SEQ ID NO:6 or a variant thereof, wherein the variant comprises a substitution of up to about 3 (e.g., 1, 2, or 3) amino acids; an HC-CDR2 comprising an amino acid sequence as set forth in SEQ ID NO:14 or a variant thereof, wherein the variant comprises a substitution of up to about 3 (e.g., 1, 2, or 3) amino acids; and an HC-CDR3 comprising an amino acid sequence as set forth in SEQ ID NO:21 or a variant thereof, wherein the variant comprises a substitution of up to about 3 (e.g., 1, 2, or 3) amino acids; and a VL comprising: an LC-CDR1 comprising an amino acid sequence as set forth in any one of SEQ ID NOs:29 or 83 or a variant thereof, wherein the variant comprises a substitution of up to about 3 (e.g., 1, 2, or 3) amino acids;
  • the anti-LIGHT antibody comprises a VH comprising: a HC-CDR1 comprising the amino acid sequence shown in SEQ ID NO:6, a HC-CDR2 comprising the amino acid sequence shown in SEQ ID NO:14, and a HC-CDR3 comprising the amino acid sequence shown in SEQ ID NO:21; and a VL comprising: a LC -CDR1 comprising the amino acid sequence shown in any one of SEQ ID NOs:29 or 83, a LC-CDR2 comprising the amino acid sequence shown in SEQ ID NO:35, and a LC-CDR3 comprising the amino acid sequence shown in SEQ ID NO:43.
  • the anti-LIGHT antibody comprises a VH comprising: a HC-CDR1 comprising the amino acid sequence of SEQ ID NO:6, a HC-CDR2 comprising the amino acid sequence of SEQ ID NO:14, a HC-CDR3 comprising the amino acid sequence of SEQ ID NO:21, or a variant of the VH comprising up to about 5 amino acid substitutions in its HC-CDRs; and a VL comprising: a LC-CDR1 comprising the amino acid sequence of SEQ ID NO:29, a LC-CDR2 comprising the amino acid sequence of SEQ ID NO:35, a LC-CDR3 comprising the amino acid sequence of SEQ ID NO:43, or a variant of the VL comprising up to about 5 amino acid substitutions in its LC-CDRs.
  • the anti-LIGHT antibody comprises a VH comprising: a HC-CDR1 comprising the amino acid sequence of SEQ ID NO:6, a HC-CDR2 comprising the amino acid sequence of SEQ ID NO:14, and a HC-CDR3 comprising the amino acid sequence of SEQ ID NO:21; and a VL comprising: a LC-CDR1 comprising the amino acid sequence of SEQ ID NO:29, a LC-CDR2 comprising the amino acid sequence of SEQ ID NO:35, and a LC-CDR3 comprising the amino acid sequence of SEQ ID NO:43.
  • the anti-LIGHT antibody comprises a VH comprising: a HC-CDR1 comprising the amino acid sequence of SEQ ID NO:6, a HC-CDR2 comprising the amino acid sequence of SEQ ID NO:14, a HC-CDR3 comprising the amino acid sequence of SEQ ID NO:21, or a variant of the VH comprising up to about 5 amino acid substitutions in the HC-CDRs; and a VL comprising: a LC-CDR1 comprising the amino acid sequence of SEQ ID NO:83, a LC-CDR2 comprising the amino acid sequence of SEQ ID NO: NO:35, LC-CDR3, which comprises the amino acid sequence of SEQ ID NO:43, or a variant of said V L , which comprises substitutions of up to about 5 amino acids in its LC-CDRs.
  • the anti-LIGHT antibody comprises a VH comprising: a HC-CDR1 comprising the amino acid sequence of SEQ ID NO:6, a HC-CDR2 comprising the amino acid sequence of SEQ ID NO:14, and a HC-CDR3 comprising the amino acid sequence of SEQ ID NO:21; and a VL comprising: a LC-CDR1 comprising the amino acid sequence of SEQ ID NO:83, a LC-CDR2 comprising the amino acid sequence of SEQ ID NO:35, and a LC-CDR3 comprising the amino acid sequence of SEQ ID NO:43.
  • the anti-LIGHT antibody comprises: a VH comprising HC-CDR1, HC-CDR2 and HC-CDR3 comprised by the VH as shown in any one of the amino acid sequences of SEQ ID NOs: 60, 84-85, and a VL comprising LC-CDR1, LC-CDR2 and LC-CDR3 comprised by the VL as shown in any one of the amino acid sequences of SEQ ID NOs: 72, 86-91.
  • the anti-LIGHT antibody comprises a VH comprising HC-CDR1, HC-CDR2 and HC-CDR3 comprised by VH as shown in the amino acid sequence of SEQ ID NO:60; and a VL comprising LC-CDR1, LC-CDR2 and LC-CDR3 comprised by VL as shown in the amino acid sequence of SEQ ID NO:72.
  • the anti-LIGHT antibody comprises a VH comprising HC-CDR1, HC-CDR2 and HC-CDR3 comprised by VH as shown in the amino acid sequence of SEQ ID NO:85; and a VL comprising LC-CDR1, LC-CDR2 and LC-CDR3 comprised by VL as shown in the amino acid sequence of SEQ ID NO:90.
  • the anti-LIGHT antibody comprises: a VH comprising an amino acid sequence as shown in any one of SEQ ID NOs:60, 84-85 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence shown in any one of SEQ ID NOs:60, 84-85; and a VL comprising an amino acid sequence as shown in any one of SEQ ID NOs:72, 86-91 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence shown in any one of SEQ ID NOs:72, 86-91.
  • the anti-LIGHT antibody comprises a VH comprising the amino acid sequence shown in any one of SEQ ID NOs : 60, 84-85, and a VL comprising the amino acid sequence shown in any one of SEQ ID NOs: 72, 86-91.
  • the anti-LIGHT antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 60, or a variant thereof, which has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 60; and a VL comprising the amino acid sequence of SEQ ID NO: 72, or a variant thereof, which has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 72.
  • the anti-LIGHT antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 60, and a VL comprising the amino acid sequence of SEQ ID NO: 72.
  • the anti-LIGHT antibody comprises: a VH comprising the amino acid sequence of SEQ ID NO:84 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence of SEQ ID NO:84; and a VL comprising the amino acid sequence of SEQ ID NO:86 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence of SEQ ID NO:86.
  • the anti-LIGHT antibody comprises a VH comprising the amino acid sequence of SEQ ID NO:84, and a VL comprising the amino acid sequence of SEQ ID NO:86.
  • the anti-LIGHT antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 85, or a variant thereof, which has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 85; and a VL comprising the amino acid sequence of SEQ ID NO: 87, or a variant thereof, which has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 87.
  • the anti-LIGHT antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 85, and a VL comprising the amino acid sequence of SEQ ID NO: 87.
  • the anti-LIGHT antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 84, or a variant thereof, which has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 84; and a VL comprising the amino acid sequence of SEQ ID NO: 88, or a variant thereof, which has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 88.
  • the anti-LIGHT antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 84, and a VL comprising the amino acid sequence of SEQ ID NO: 88.
  • the anti-LIGHT antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 84, or a variant thereof, which has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 84; and a VL comprising the amino acid sequence of SEQ ID NO: 89, or a variant thereof, which has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 89.
  • the anti-LIGHT antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 84, and a VL comprising the amino acid sequence of SEQ ID NO: 89.
  • the anti-LIGHT antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 85, or a variant thereof, which has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 85; and a VL comprising the amino acid sequence of SEQ ID NO: 90, or a variant thereof, which has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 90.
  • the anti-LIGHT antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 85, and a VL comprising the amino acid sequence of SEQ ID NO: 90.
  • the anti-LIGHT antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 84, or a variant thereof, which has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 84; and a VL comprising the amino acid sequence of SEQ ID NO: 91, or a variant thereof, which has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 91.
  • the anti-LIGHT antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 84, and a VL comprising the amino acid sequence of SEQ ID NO: 91.
  • the anti-LIGHT antibody comprises a heavy chain variable domain ( VH ), wherein the VH comprises: a heavy chain complementary determining region (HC-CDR) 1 comprising SYNVH (SEQ ID NO: 7); a HC-CDR2 comprising AVYPGNGDTSYNQKFKG (SEQ ID NO: 15); and HC-CDR3 comprising GSYYYTSSYFDH (SEQ ID NO: 22); and a light chain variable domain ( VL ), wherein VL comprises: a light chain complementarity determining region (LC-CDR) 1 comprising KASQSVDFDGDSYMN (SEQ ID NO: 29); LC-CDR2 comprising TASNLES (SEQ ID NO: 36); and LC-CDR3 comprising QQSYEDPFT (SEQ ID NO: 44).
  • VH comprises: a heavy chain complementary determining region (HC-CDR) 1 comprising SYNVH (SEQ ID NO: 7); a HC-CDR2
  • the anti-LIGHT antibody comprises a VH comprising: a HC-CDR1 comprising the amino acid sequence shown in SEQ ID NO:7 or a variant thereof, wherein the variant comprises substitutions of up to about 3 (eg, 1, 2, or 3) amino acids; a HC-CDR2 comprising the amino acid sequence shown in SEQ ID NO:15 or a variant thereof, wherein the variant comprises substitutions of up to about 3 (eg, 1, 2, or 3) amino acids; and a HC-CDR3 comprising the amino acid sequence shown in SEQ ID NO:22 or a variant thereof, wherein the variant comprises substitutions of up to about 3 (eg, 1, 2, or 3) amino acids.
  • the anti-LIGHT antibody comprises a VH comprising: a HC-CDR1 comprising the amino acid sequence of SEQ ID NO:7, a HC-CDR2 comprising the amino acid sequence of SEQ ID NO:15, and a HC-CDR3 comprising the amino acid sequence of SEQ ID NO:22.
  • the anti-LIGHT antibody comprises a VL comprising: a LC-CDR1 comprising the amino acid sequence shown in SEQ ID NO:29 or a variant thereof, wherein the variant comprises substitutions of up to about 3 (e.g., 1, 2 or 3) amino acids; a LC-CDR2 comprising the amino acid sequence shown in SEQ ID NO:36 or a variant thereof, wherein the variant comprises substitutions of up to about 3 (e.g., 1, 2 or 3) amino acids; and a LC-CDR3 comprising the amino acid sequence shown in SEQ ID NO:44 or a variant thereof, wherein the variant comprises substitutions of up to about 3 (e.g., 1, 2 or 3) amino acids.
  • the anti-LIGHT antibody comprises a VL comprising: a LC-CDR1 comprising the amino acid sequence of SEQ ID NO:29, a LC-CDR2 comprising the amino acid sequence of SEQ ID NO:36, and a LC-CDR3 comprising the amino acid sequence of SEQ ID NO:44.
  • the anti-LIGHT antibody comprises a VH comprising: an HC-CDR1 comprising the amino acid sequence set forth in SEQ ID NO:7 or a variant thereof, wherein the variant comprises a substitution of up to about 3 (e.g., 1, 2, or 3) amino acids; an HC-CDR2 comprising the amino acid sequence set forth in SEQ ID NO:15 or a variant thereof, wherein the variant comprises a substitution of up to about 3 (e.g., 1, 2, or 3) amino acids; and an HC-CDR3 comprising the amino acid sequence set forth in SEQ ID NO:22 or a variant thereof, wherein the variant comprises a substitution of up to about 3 (e.g., 1, 2, or 3) amino acids; and a VL comprising: an LC-CDR1 comprising the amino acid sequence set forth in SEQ ID NO:29 or a variant thereof, wherein the variant comprises a substitution of up to about 3 (e.g., 1, 2, or 3) amino acids; an LC-CDR2
  • the anti-LIGHT antibody comprises a VH comprising: a HC-CDR1 comprising the amino acid sequence shown in SEQ ID NO:7, a HC-CDR2 comprising the amino acid sequence shown in SEQ ID NO:15, and a HC-CDR3 comprising the amino acid sequence shown in SEQ ID NO:22; and a VL comprising: a LC -CDR1 comprising the amino acid sequence shown in SEQ ID NO:29, a LC-CDR2 comprising the amino acid sequence shown in SEQ ID NO:36, and a LC-CDR3 comprising the amino acid sequence shown in SEQ ID NO:44.
  • the anti-LIGHT antibody comprises a VH comprising: a HC-CDR1 comprising the amino acid sequence of SEQ ID NO:7, a HC-CDR2 comprising the amino acid sequence of SEQ ID NO:15, a HC-CDR3 comprising the amino acid sequence of SEQ ID NO:22, or a variant of the VH comprising up to about 5 amino acid substitutions in its HC-CDRs; and a VL comprising: a LC-CDR1 comprising the amino acid sequence of SEQ ID NO:29, a LC-CDR2 comprising the amino acid sequence of SEQ ID NO:36, a LC-CDR3 comprising the amino acid sequence of SEQ ID NO:44, or a variant of the VL comprising up to about 5 amino acid substitutions in its LC-CDRs.
  • the anti-LIGHT antibody comprises a VH comprising: a HC-CDR1 comprising the amino acid sequence of SEQ ID NO:7, a HC-CDR2 comprising the amino acid sequence of SEQ ID NO:15, and a HC-CDR3 comprising the amino acid sequence of SEQ ID NO:22; and a VL comprising: a LC-CDR1 comprising the amino acid sequence of SEQ ID NO:29, a LC-CDR2 comprising the amino acid sequence of SEQ ID NO:36, and a LC-CDR3 comprising the amino acid sequence of SEQ ID NO:44.
  • the anti-LIGHT antibody comprises a VH comprising HC-CDR1, HC-CDR2 and HC-CDR3 comprised by the VH as shown in any one of the amino acid sequences of SEQ ID NOs:61, 92-94; and a VL comprising LC-CDR1, LC-CDR2 and LC-CDR3 comprised by the VL as shown in any one of the amino acid sequences of SEQ ID NOs:73, 95-99.
  • the anti-LIGHT antibody comprises a VH comprising HC-CDR1, HC-CDR2 and HC-CDR3 comprised by VH as shown in the amino acid sequence of SEQ ID NO:61; and a VL comprising LC-CDR1, LC-CDR2 and LC-CDR3 comprised by VL as shown in the amino acid sequence of SEQ ID NO:73.
  • the anti-LIGHT antibody comprises: a VH comprising an amino acid sequence as shown in any one of SEQ ID NOs:61, 92-94 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence shown in any one of SEQ ID NOs:61, 92-94; and a VL comprising an amino acid sequence as shown in any one of SEQ ID NOs:73, 95-99 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence shown in any one of SEQ ID NOs:73, 95-99.
  • the anti-LIGHT antibody comprises a VH comprising the amino acid sequence shown in any one of SEQ ID NOs : 61, 92-94, and a VL comprising the amino acid sequence shown in any one of SEQ ID NOs: 73, 95-99.
  • the anti-LIGHT antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 61, or a variant thereof, which has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 61; and a VL comprising the amino acid sequence of SEQ ID NO: 73, or a variant thereof, which has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 73.
  • the anti-LIGHT antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 61, and a VL comprising the amino acid sequence of SEQ ID NO: 73.
  • the anti-LIGHT antibody comprises: a VH comprising the amino acid sequence of SEQ ID NO:92 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence of SEQ ID NO:92; and a VL comprising the amino acid sequence of SEQ ID NO:95 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence of SEQ ID NO:95.
  • the anti-LIGHT antibody comprises a VH comprising the amino acid sequence of SEQ ID NO:92, and a VL comprising the amino acid sequence of SEQ ID NO:95.
  • the anti-LIGHT antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 93, or a variant thereof, which has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 93; and a VL comprising the amino acid sequence of SEQ ID NO: 96, or a variant thereof, which has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 96.
  • the anti-LIGHT antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 93, and a VL comprising the amino acid sequence of SEQ ID NO: 96.
  • the anti-LIGHT antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 92, or a variant thereof, which has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 92; and a VL comprising the amino acid sequence of SEQ ID NO: 96, or a variant thereof, which has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 96.
  • the anti-LIGHT antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 92, and a VL comprising the amino acid sequence of SEQ ID NO: 96.
  • the anti-LIGHT antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 94, or a variant thereof, which has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 94; and a VL comprising the amino acid sequence of SEQ ID NO: 97, or a variant thereof, which has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 97.
  • the anti-LIGHT antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 94, and a VL comprising the amino acid sequence of SEQ ID NO: 97.
  • the anti-LIGHT antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 94, or a variant thereof, which has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 94; and a VL comprising the amino acid sequence of SEQ ID NO: 98, or a variant thereof, which has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 98.
  • the anti-LIGHT antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 94, and a VL comprising the amino acid sequence of SEQ ID NO: 98.
  • the anti-LIGHT antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 93, or a variant thereof, which has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 93; and a VL comprising the amino acid sequence of SEQ ID NO: 98, or a variant thereof, which has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 98.
  • the anti-LIGHT antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 93, and a VL comprising the amino acid sequence of SEQ ID NO: 98.
  • the anti-LIGHT antibody comprises: a VH comprising the amino acid sequence of SEQ ID NO: 92 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, and a VL comprising the amino acid sequence of SEQ ID NO: 98 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99 % ) sequence identity to the amino acid sequence of SEQ ID NO: 98.
  • the anti-LIGHT antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 92, and a VL comprising the amino acid sequence of SEQ ID NO: 98.
  • the anti-LIGHT antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 94, or a variant thereof, which has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 94; and a VL comprising the amino acid sequence of SEQ ID NO: 99, or a variant thereof, which has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 99.
  • the anti-LIGHT antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 94, and a VL comprising the amino acid sequence of SEQ ID NO: 99.
  • the anti-LIGHT antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 92, or a variant thereof, which has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 92; and a VL comprising the amino acid sequence of SEQ ID NO: 99, or a variant thereof, which has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 99.
  • the anti-LIGHT antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 92, and a VL comprising the amino acid sequence of SEQ ID NO: 99.
  • the above-mentioned amino acid substitutions are limited to the "exemplary substitutions” shown in Table 4 herein. In some embodiments, the amino acid substitutions are limited to the "preferred substitutions” shown in Table 4 herein.
  • functional epitopes can be resolved by combined alanine scanning.
  • combined alanine scanning technology can be used to identify amino acids in LIGHT protein that are necessary for interaction with anti-LIGHT antibodies.
  • the epitope is conformational, and the crystal structure of the anti-LIGHT antibody bound to the LIGHT protein can be used to identify the epitope.
  • the present application provides antibodies that competitively bind to LIGHT with any anti-LIGHT antibody described herein.
  • antibodies that can competitively bind to an epitope on LIGHT with any anti-LIGHT antibody described herein are provided.
  • anti-LIGHT antibodies are provided that bind to the same epitope as an anti-LIGHT antibody molecule comprising V H and V L , wherein the V H comprises an amino acid sequence shown in any one of SEQ ID NOs: 46-61, 92-94, and the V L comprises an amino acid sequence shown in any one of SEQ ID NOs: 62-73, 95-99.
  • anti-LIGHT antibodies that competitively bind to LIGHT with an anti-LIGHT antibody comprising V H and V L , wherein the V H comprises an amino acid sequence shown in any one of SEQ ID NOs: 46-61, 92-94, and the V L comprises an amino acid sequence shown in any one of SEQ ID NOs: 62-73, 95-99.
  • competition experiments can be used to identify monoclonal antibodies that compete with the anti-LIGHT antibodies described herein for binding to LIGHT. Competition experiments can determine whether two antibodies bind to the same epitope by recognizing the same or spatially overlapping epitopes or by competitively inhibiting the binding of another antibody to the antigen by one antibody. In certain embodiments, such competing antibodies bind to the same epitope as the antibodies described herein.
  • Some exemplary competition experiments include, but are not limited to, Harlow and Lane (1988) Antibodies: A Laboratory Manual ch. 14 (Cold Spring Harbor Laboratory, Cold Spring Harbor, NY). Detailed exemplary methods for parsing epitopes bound by antibodies are described in Morris (1996) "Epitope Mapping Protocols," in Methods in Molecular Biology vol.
  • the antibody competing with the anti-LIGHT antibody described herein is a chimeric antibody, a humanized antibody, or a fully human antibody.
  • anti-LIGHT antibody sequences are shown in Tables 2 and 3, wherein CDR numbering is performed according to the Kabat definition. Those skilled in the art will recognize that there are a variety of known algorithms to predict the position of CDRs and define antibody light and heavy chain variable regions. Antibodies comprising CDRs, VH and/or VL sequences of antibodies as described herein, but based on prediction algorithms rather than those exemplified in the following tables are also within the scope of this application.
  • LIGHT lymphotoxin-like receptor inducibly expressed on T lymphocytes that competes with herpes simplex virus glycoprotein D for binding to HVEM
  • TNFSF tumor necrosis factor superfamily
  • LIGHT is a type II transmembrane protein containing 240 amino acids, forming a homotrimer on the cell surface.
  • LIGHT is also known as tumor necrosis factor superfamily member 14 (TNFSF14), TL5, LTg, HVEML or CD258.
  • LIGHT is a T cell co-stimulatory molecule that can induce T cell proliferation and cytokine production (Tamada et al., 2000, Nat Med).
  • LIGHT can also induce inflammatory responses in monocytes and endothelial cells (Otterda et al., 2006, Blood; Chang et al., 2005, J Biomed Sci). LIGHT binds to three different receptors expressed on different cell types: the herpes virus entry regulator HVEM expressed on T cells and B cells, the lymphotoxin beta receptor LT ⁇ R and the decoy receptor 3 expressed on stromal cells and non-hematopoietic cells. LIGHT on dendritic cells and T cells enhances T cell proliferation and cytokine production. LIGHT can directly co-stimulate T cell responses. The role of LIGHT in various inflammatory diseases and conditions has been demonstrated using various models using LIGHT-deficient models and LIGHT-overexpressing transgenic animals. Overexpression of LIGHT in mice resulted in excessive overproduction of activated peripheral T-cell populations and spontaneous development of severe autoimmune diseases (Wang et al., 2001, J Clin Invest.).
  • LIGHT mediates its biological effects by binding to three TNF superfamily receptors, including the lymphotoxin ⁇ receptor (LT ⁇ R) (Crowe et al., 1994, Science 264707-10, Browning et al., 1997, J Immunol 159 3288-98), the herpes simplex virus entry mediator (HVEM) (Montgomery et al., 1996, Cell 87(3)427-36) and the decoy receptor 3 (DcR3) (Yu et al., 1999, J Biol Chem 274 13733-6).
  • L ⁇ R lymphotoxin ⁇ receptor
  • HVEM herpes simplex virus entry mediator
  • DcR3 decoy receptor 3
  • Lymphotoxin ⁇ receptor (LT ⁇ R) signaling coordinates lymphocyte neogenesis and subsequent tertiary lymphoid structures (TLS), and is associated with severe chronic inflammatory diseases in multiple organ systems.
  • Conlon TM et al. demonstrated that inhibition of LT ⁇ R signaling can activate Wnt-induced lung regeneration (Conlon TM et al., 2020, Nature 588(7836):151-156).
  • blockade of LT ⁇ R signaling inhibited epithelial non-canonical NF- ⁇ B activation and reduced TGF ⁇ signaling in the airways, inducing regeneration by preventing epithelial cell death and activating Wnt/ ⁇ -catenin signaling in alveolar epithelial progenitor cells.
  • LIGHT on activated T cells can directly transmit signals to other T cells expressing HVEM, or it can indirectly act through HVEM and/or LT ⁇ R expressed on immature DC cells or SC cells to stimulate these auxiliary cells to secrete proinflammatory factors. More and more experimental evidence shows that LIGHT expressed on DC or T cells can co-stimulate and enhance T cell proliferation and cytokine secretion (Tamada. K et al., 2000, J. Immunol. 164, 4105-4110.).
  • LIGHT-Ig recombinant fusion protein can activate NF- ⁇ B and AP-1, co-stimulate T cell proliferation and IFN- ⁇ secretion (Granger et al., 2003, Cytokine Growth Factor Rev. 14, 289-296). This enhanced T cell activation is mediated by HVEM signaling because LT ⁇ R is not expressed on mature T cells. The interaction of LIGHT with HVEM expressed by other cell types can also trigger various functional activities.
  • soluble or membrane-bound LIGHT expressed on activated T cells when contacted with HVEM expressed on immature DC cells, can induce DC cell maturation and enhance the allogeneic stimulatory activity when CD40L-Ig is added (Morel et al., 2001, J. Immunol. 167, 2479-2486).
  • mice constitutively expressing LIGHT were detected with hyperactivated T cell populations, which increased the risk of autoimmunity in mice, characterized by severe infiltration of effector cells in peripheral tissues of mice (Wang et al., 2005, J Immunol 174 8173-82; Shaikh et al., 2001, J Immunol 167 6330-7; Wang et al., 2001, J Immunol 1675099-105; Wang et al., 2004, J Clin Invest 113 826-35).
  • the interaction of HVEM-LIGHT can promote the pathogenesis of graft-versus-host disease (GVHD).
  • HVEM-LIGHT plays a dominant role in the survival of pathogenic memory Th2 cells. Interruption of the interaction of HVEM-LIGHT inhibits the accumulation of inflammatory memory Th2 cells in the lungs.
  • light -/- donor CD4+ T cells cannot be maintained after antigen exposure in vivo, co-transfer of wild-type and light-/- donor T cells can rescue the survival defect of light-/- donor T cells, indicating that HVEM induces cell survival signals into T cells by interacting with LIGHT expressed on neighboring antigen-specific T cells.
  • This study shows that HVEM expressed by CD4+ T cells can induce cell survival signals and control T cell-driven hypersensitivity pneumonitis (Soroosh et al., 2011, J Exp Med 208:797–809).
  • DcR3 also known as tumor necrosis factor receptor superfamily member 6B (TNFRSF6B)
  • TNFRSF6B tumor necrosis factor receptor superfamily member 6B
  • DcR3 binds to LIGHT and inhibits the interaction between HVEM and LIGHT (Jiang M. 2016, Med Sci Monit. 22:1850–7).
  • the anti-LIGHT antibody is a full-length anti-LIGHT antibody.
  • the full-length anti-LIGHT antibody is IgA, IgD, IgE, IgG or IgM.
  • the full-length anti-LIGHT antibody comprises an IgG constant region, such as a constant region of IgG1, IgG2, IgG3, IgG4 or a variant thereof.
  • the full-length anti-LIGHT antibody comprises a ⁇ light chain constant region.
  • the full-length anti-LIGHT antibody comprises a ⁇ light chain constant region.
  • the full-length anti-LIGHT antibody is a full-length human anti-LIGHT antibody.
  • the full-length anti-LIGHT antibody comprises a mouse immunoglobulin Fc sequence. In some embodiments, the full-length anti-LIGHT antibody comprises an Fc sequence that has been altered or otherwise altered so that it has enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) effector functions.
  • ADCC antibody-dependent cell-mediated cytotoxicity
  • CDC complement-dependent cytotoxicity
  • a full-length anti-LIGHT antibody comprising an IgG1 constant region, wherein the anti-LIGHT antibody specifically binds to LIGHT.
  • the IgG1 is a human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:74.
  • the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO:76.
  • the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO:77.
  • the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:74 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO:76.
  • the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:74 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO:77.
  • a full-length anti-LIGHT antibody comprising an IgG2 constant region, wherein the anti-LIGHT antibody specifically binds to LIGHT.
  • the IgG2 is a human IgG2.
  • the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 77.
  • a full-length anti-LIGHT antibody comprising an IgG3 constant region, wherein the anti-LIGHT antibody specifically binds to LIGHT.
  • the IgG3 is human IgG3.
  • the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO:76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO:77.
  • a full-length anti-LIGHT antibody comprising an IgG4 constant region, wherein the anti-LIGHT antibody specifically binds to LIGHT.
  • the IgG4 is a human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:75.
  • the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO:76.
  • the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO:77.
  • the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:75 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO:76.
  • the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:75 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO:77.
  • a full-length anti-LIGHT antibody comprising an IgG1 constant region
  • the anti-LIGHT antibody comprises: a) a heavy chain variable domain, the heavy chain variable domain comprising: HC-CDR1, which comprises the amino acid sequence shown in any one of SEQ ID NOs: 1-7 or a variant thereof, wherein the variant comprises a substitution of up to about 3 (e.g., 1, 2 or 3) amino acids; HC-CDR2, which comprises the amino acid sequence shown in any one of SEQ ID NOs: 8-15 or a variant thereof, wherein the variant comprises a substitution of up to about 3 (e.g., 1, 2 or 3) amino acids; and HC-CDR3, which comprises the amino acid sequence shown in any one of SEQ ID NOs: 16-22 or a variant thereof, wherein the variant comprises a substitution of up to about 3 (e.g., 1, 2 or 3) amino acids.
  • a light chain variable domain comprising: a LC-CDR1 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 23-29, 83 or a variant thereof, said variant comprising a substitution of up to about 3 (e.g., 1, 2 or 3) amino acids, a LC-CDR2 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 30-36 or a variant thereof, said variant comprising a substitution of up to about 3 (e.g., 1, 2 or 3) amino acids; and a LC-CDR3 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 37-44 or a variant thereof, said variant comprising a substitution of up to about 3 (e.g., 1, 2 or 3) amino acids.
  • a LC-CDR1 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 23-29, 83 or a variant thereof, said variant comprising a substitution of up to about 3 (e.g., 1,
  • the IgG1 is a human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 74.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 76.
  • the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 77.
  • the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 74 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 76.
  • the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 74 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 77.
  • a full-length anti-LIGHT antibody comprising an IgG2 constant region
  • the anti-LIGHT antibody comprises: a) a heavy chain variable domain, the heavy chain variable domain comprising: HC-CDR1 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 1-7 or a variant thereof, wherein the variant comprises a substitution of up to about 3 (e.g., 1, 2 or 3) amino acids; HC-CDR2 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 8-15 or a variant thereof, wherein the variant comprises a substitution of up to about 3 (e.g., 1, 2 or 3) amino acids; and HC-CDR3 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 16-22 or a variant thereof, wherein the variant comprises a substitution of up to about 3 (e.g., 1, 2 or 3) amino acids; and b) a light chain variable A light chain variable domain comprising: a LC-
  • the IgG2 is a human IgG2.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 77.
  • a full-length anti-LIGHT antibody comprising an IgG3 constant region
  • the anti-LIGHT antibody comprises: a) a heavy chain variable domain, the heavy chain variable domain comprising: HC-CDR1, which comprises the amino acid sequence shown in any one of SEQ ID NOs: 1-7 or a variant thereof, wherein the variant comprises a substitution of up to about 3 (e.g., 1, 2 or 3) amino acids, HC-CDR2, which comprises the amino acid sequence shown in any one of SEQ ID NOs: 8-15 or a variant thereof, wherein the variant comprises a substitution of up to about 3 (e.g., 1, 2 or 3) amino acids; and HC-CDR3, which comprises the amino acid sequence shown in any one of SEQ ID NOs: 16-22 or a variant thereof, wherein the variant comprises a substitution of up to about 3 (e.g., 1, 2 or 3) amino acids.
  • a light chain variable domain comprising: a LC-CDR1 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 23-29, 83 or a variant thereof, wherein the variant comprises a substitution of up to about 3 (e.g., 1, 2 or 3) amino acids; a LC-CDR2 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 30-36 or a variant thereof, wherein the variant comprises a substitution of up to about 3 (e.g., 1, 2 or 3) amino acids; and a LC-CDR3 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 37-44 or a variant thereof, wherein the variant comprises a substitution of up to about 3 (e.g., 1, 2 or 3) amino acids.
  • a LC-CDR1 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 23-29, 83 or a variant thereof, wherein the variant comprises a substitution of up to about 3 (e.
  • the IgG3 is a human IgG3.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 77.
  • a full-length anti-LIGHT antibody comprising an IgG4 constant region
  • the anti-LIGHT antibody comprises: a) a heavy chain variable domain, the heavy chain variable domain comprising: HC-CDR1 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 1-7 or a variant thereof, wherein the variant comprises a substitution of up to about 3 (e.g., 1, 2 or 3) amino acids; HC-CDR2 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 8-15 or a variant thereof, wherein the variant comprises a substitution of up to about 3 (e.g., 1, 2 or 3) amino acids; and HC-CDR3 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 16-22 or a variant thereof, wherein the variant comprises a substitution of up to about 3 (e.g., 1, 2 or 3) amino acids; and b) a light chain variable domain, the light chain variable domain comprising: LC-
  • the IgG4 is a human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:75.
  • the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO:76.
  • the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO:77.
  • the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 77.
  • a full-length anti-LIGHT antibody comprising an IgG1 constant region
  • the anti-LIGHT antibody comprises: a) a heavy chain variable domain
  • the heavy chain variable domain comprises: HC-CDR1 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 1-7, HC-CDR2 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 8-15, and HC-CDR3 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 16-22, or a variant of the heavy chain variable domain comprising up to about 5
  • a light chain variable domain comprising: a LC-CDR1 comprising an amino acid sequence as set forth in any one of SEQ ID NOs: 23-29, 83, a LC-CDR2 comprising an amino acid sequence as set forth in any one of SEQ ID NOs: 30-36, and a LC-CDR3 comprising an amino acid sequence as set forth in any one of S
  • the IgG1 is human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 74.
  • the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 76.
  • the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 77.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 76.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 77.
  • a full-length anti-LIGHT antibody comprising an IgG4 constant region
  • the anti-LIGHT antibody comprises a) a heavy chain variable domain, the heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 1-7, HC-CDR2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 8-15, and HC-CDR3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 16-22, or a variant of the heavy chain variable domain comprising up to about 5 ( and b) a light chain variable domain comprising: a LC-CDR1 comprising an amino acid sequence as set forth in any one of SEQ ID NOs: 23-29, 83, a LC-CDR2 comprising an amino acid sequence as set forth in any one of SEQ ID NOs: 30-36, and a LC-CDR3 comprising an amino acid sequence as set forth in any one of SEQ ID NOs:
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 75.
  • the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 76.
  • the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 77.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 76.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 77.
  • a full-length anti-LIGHT antibody comprising an IgG1 constant region
  • the anti-LIGHT antibody comprises: a) a heavy chain variable domain, the heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence shown in any one of SEQ ID NOs: 1-7, HC-CDR2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 8-15, and HC- CDR3, which comprises the amino acid sequence shown in any one of SEQ ID NOs: 16-22; and b) a light chain variable domain, the light chain variable domain comprising: LC-CDR1, which comprises the amino acid sequence shown in any one of SEQ ID NOs: 23-29, 83, LC-CDR2, which comprises the amino acid sequence shown in any one of SEQ ID NOs: 30-36, and LC-CDR3, which comprises the amino acid sequence shown in any one of SEQ ID NOs: 37-44.
  • the IgG1 is human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 74.
  • the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 76.
  • the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 77.
  • the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 74 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 76.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77.
  • a full-length anti-LIGHT antibody comprising an IgG4 constant region comprising: a) a heavy chain variable domain comprising: HC-CDR1 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 1-7, HC-CDR2 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 8-15, and HC-CDR3 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 16-22; and b) a light chain variable domain comprising: LC-CDR1 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 23-29, 83, LC-CDR2 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 30-36, and LC-CDR3 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 37-44.
  • the IgG4 is a human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 75.
  • the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 76.
  • the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 77.
  • the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 75 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 76.
  • the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 75 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 77.
  • a full-length anti-LIGHT antibody comprising an IgG1 constant region
  • the anti-LIGHT antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO:8, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO:16; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:23, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:30, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:37.
  • the IgG1 is a human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 76.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 77.
  • the IgG1 is a human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77.
  • a full-length anti-LIGHT antibody comprising an IgG1 constant region
  • the anti-LIGHT antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO:2, HC-CDR2 comprising the amino acid sequence of SEQ ID NO:10, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO:17; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:24, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:31, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:38.
  • the IgG1 is a human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 76.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 77.
  • a full-length anti-LIGHT antibody comprising an IgG1 constant region
  • the anti-LIGHT antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO:2, HC-CDR2 comprising the amino acid sequence of SEQ ID NO:10, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO:17; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:25, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:31, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:39.
  • the IgG1 is a human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 76.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 77.
  • a full-length anti-LIGHT antibody comprising an IgG1 constant region
  • the anti-LIGHT antibody comprises: a) a heavy chain variable domain, the heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 3, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 11, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 18; and b) a light chain variable domain comprising: a LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 26, a LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 32, and a LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 40.
  • the IgG1 is a human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 74.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 76.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 77.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 76.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 77.
  • a full-length anti-LIGHT antibody comprising an IgG1 constant region
  • the anti-LIGHT antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO:3, HC-CDR2 comprising the amino acid sequence of SEQ ID NO:11, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO:18; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:26, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:32, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:41.
  • the IgG1 is a human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 76.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 77.
  • a full-length anti-LIGHT antibody comprising an IgG1 constant region
  • the anti-LIGHT antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO:4, HC-CDR2 comprising the amino acid sequence of SEQ ID NO:12, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO:19; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:27, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:33, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:42.
  • the IgG1 is a human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 76.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 77.
  • a full-length anti-LIGHT antibody comprising an IgG1 constant region
  • the anti-LIGHT antibody comprises: a) a heavy chain variable domain, the heavy chain variable domain comprising: HC-CDR1, which comprises the amino acid sequence of SEQ ID NO: 5, HC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 13, and HC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 20; and b) a light chain variable domain, the light chain variable domain comprising: LC-CDR1, which comprises the amino acid sequence of SEQ ID NO:28, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO:34, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO:43.
  • the IgG1 is human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77.
  • a full-length anti-LIGHT antibody comprising an IgG1 constant region
  • the anti-LIGHT antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO:6, HC-CDR2 comprising the amino acid sequence of SEQ ID NO:14, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO:21; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:29, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:35, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:43.
  • the IgG1 is a human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 76.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 77.
  • a full-length anti-LIGHT antibody comprising an IgG1 constant region
  • the anti-LIGHT antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO:6, HC-CDR2 comprising the amino acid sequence of SEQ ID NO:14, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO:21; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:83, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:35, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:43.
  • the IgG1 is a human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 76.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 77.
  • a full-length anti-LIGHT antibody comprising an IgG1 constant region
  • the anti-LIGHT antibody comprises: a) a heavy chain variable domain, the heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 7, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 15, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 22; and b) a light chain variable domain, the light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 29, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 36, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 44.
  • the IgG1 is a human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:74.
  • the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO:76.
  • the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO:77.
  • the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:74 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO:76.
  • the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:74 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO:77.
  • a full-length anti-LIGHT antibody comprising an IgG4 constant region
  • the anti-LIGHT antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 8, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 16; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 23, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 30, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 37.
  • the IgG4 is a human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 75.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 76.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 77.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 76.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 77.
  • a full-length anti-LIGHT antibody comprising an IgG4 constant region
  • the anti-LIGHT antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO:9, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO:16; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:23, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:30, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:37.
  • the IgG4 is a human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 76.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 77.
  • a full-length anti-LIGHT antibody comprising an IgG4 constant region
  • the anti-LIGHT antibody comprises: a) a heavy chain variable domain, the heavy chain variable domain comprising: HC-CDR1, which comprises the amino acid sequence of SEQ ID NO: 2, HC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 10, and HC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 17; and b) a light chain variable domain, the light chain variable domain comprising: LC-CDR1, which comprises the amino acid sequence of SEQ ID NO: 24, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 31, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 38.
  • the IgG4 is a human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 75.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 76.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 77.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 76.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 77.
  • a full-length anti-LIGHT antibody comprising an IgG4 constant region
  • the anti-LIGHT antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO:2, HC-CDR2 comprising the amino acid sequence of SEQ ID NO:10, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO:17; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:25, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:31, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:39.
  • the IgG4 is a human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 76.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 77.
  • a full-length anti-LIGHT antibody comprising an IgG4 constant region
  • the anti-LIGHT antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO:3, HC-CDR2 comprising the amino acid sequence of SEQ ID NO:11, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO:18; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:26, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:32, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:40.
  • the IgG4 is a human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 76.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 77.
  • a full-length anti-LIGHT antibody comprising an IgG4 constant region
  • the anti-LIGHT antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 3, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 11, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 18; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 26, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 32, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 41.
  • the IgG4 is a human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 75.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 76.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 77.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 76.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 77.
  • a full-length anti-LIGHT antibody comprising an IgG4 constant region
  • the anti-LIGHT antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO:4, HC-CDR2 comprising the amino acid sequence of SEQ ID NO:12, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO:19; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:27, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:33, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:42.
  • the IgG4 is a human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 76.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 77.
  • a full-length anti-LIGHT antibody comprising an IgG4 constant region
  • the anti-LIGHT antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO:5, HC-CDR2 comprising the amino acid sequence of SEQ ID NO:13, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO:20; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:28, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:34, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:43.
  • the IgG4 is a human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 76.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 77.
  • a full-length anti-LIGHT antibody comprising an IgG4 constant region
  • the anti-LIGHT antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO:6, HC-CDR2 comprising the amino acid sequence of SEQ ID NO:14, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO:21; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:29, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:35, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:43.
  • the IgG4 is a human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:78.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 76.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 77.
  • a full-length anti-LIGHT antibody comprising an IgG4 constant region
  • the anti-LIGHT antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO:6, HC-CDR2 comprising the amino acid sequence of SEQ ID NO:14, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO:21; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:83, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:35, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:43.
  • the IgG4 is a human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 76.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 77.
  • a full-length anti-LIGHT antibody comprising an IgG4 constant region
  • the anti-LIGHT antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO:7, HC-CDR2 comprising the amino acid sequence of SEQ ID NO:15, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO:22; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:29, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:36, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:44.
  • the IgG4 is a human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 76.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 77.
  • a full-length anti-LIGHT antibody comprising an IgG1 constant region
  • the anti-LIGHT antibody comprises: a heavy chain variable domain ( VH ), wherein the VH comprises an amino acid sequence as shown in any one of SEQ ID NOs:46-61, 84-85, 92-94 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity with the amino acid sequence as shown in any one of SEQ ID NOs:46-61, 84-85, 92-94; and a light chain variable domain ( VL ), wherein the VL comprises an amino acid sequence as shown in any one of SEQ ID NOs:62-73, 86-91, 95-99 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%
  • the IgG1 is human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 74.
  • the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 76.
  • the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 77.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 77.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 76.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 77.
  • a full-length anti-LIGHT antibody comprising an IgG2 constant region
  • the anti-LIGHT antibody comprises: a heavy chain variable domain ( VH ), wherein the VH comprises an amino acid sequence as shown in any one of SEQ ID NOs:46-61, 84-85, 92-94 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity with the amino acid sequence as shown in any one of SEQ ID NOs:46-61, 84-85, 92-94; and a light chain variable domain ( VL ), wherein the VL comprises an amino acid sequence as shown in any one of SEQ ID NOs:62-73, 86-91, 95-99 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%
  • the IgG2 is human IgG2.
  • the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO:76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO:77.
  • a full-length anti-LIGHT antibody comprising an IgG3 constant region
  • the anti-LIGHT antibody comprises: a heavy chain variable domain ( VH ), wherein the VH comprises an amino acid sequence as shown in any one of SEQ ID NOs:46-61, 84-85, 92-94 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity with the amino acid sequence as shown in any one of SEQ ID NOs:46-61, 84-85, 92-94; and a light chain variable domain ( VL ), wherein the VL comprises an amino acid sequence as shown in any one of SEQ ID NOs:62-73, 86-91, 95-99 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%
  • the IgG3 is human IgG3.
  • the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO:76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO:77.
  • a full-length anti-LIGHT antibody comprising an IgG4 constant region
  • the anti-LIGHT antibody comprises: a heavy chain variable domain ( VH ), wherein the VH comprises an amino acid sequence as shown in any one of SEQ ID NOs:46-61, 84-85, 92-94 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity with the amino acid sequence as shown in any one of SEQ ID NOs:46-61, 84-85, 92-94; and a light chain variable domain ( VL ), wherein the VL comprises an amino acid sequence as shown in any one of SEQ ID NOs:62-73, 86-91, 95-99 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:75.
  • the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO:76.
  • the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO:77.
  • the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:75 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO:76.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77.
  • a full-length anti-LIGHT antibody comprising an IgG1 constant region
  • the anti-LIGHT antibody comprises: a heavy chain variable domain ( VH ), wherein the VH comprises the amino acid sequence shown in any one of SEQ ID NOs: 46-61, 84-85, 92-94, and a light chain variable domain ( VL ), wherein the VL comprises the amino acid sequence shown in any one of SEQ ID NOs: 62-73, 86-91, 95-99.
  • the IgG1 is a human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 74.
  • the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 77. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 74 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 76. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 74 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 77.
  • a full-length anti-LIGHT antibody comprising an IgG4 constant region
  • the anti-LIGHT antibody comprises: a heavy chain variable domain ( VH ), wherein the VH comprises the amino acid sequence shown in any one of SEQ ID NOs: 46-61, 84-85, 92-94, and a light chain variable domain ( VL ), wherein the VL comprises the amino acid sequence shown in any one of SEQ ID NOs: 62-73, 86-91, 95-99.
  • the IgG4 is a human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 75.
  • the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 77. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 75 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 76. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 75 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 77.
  • a full-length anti-LIGHT antibody comprising an IgG1 constant region comprising: a VH comprising the amino acid sequence of SEQ ID NO:46 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:46; and a VL comprising the amino acid sequence of SEQ ID NO:62 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:62.
  • the IgG1 is a human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77.
  • a full-length anti-LIGHT antibody comprising an IgG1 constant region comprising: a VH comprising the amino acid sequence of SEQ ID NO:47 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:47; and a VL comprising the amino acid sequence of SEQ ID NO:63 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:63.
  • the IgG1 is human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 76. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 77. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 77.
  • a full-length anti-LIGHT antibody comprising an IgG1 constant region comprising: a VH comprising the amino acid sequence of SEQ ID NO:48 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:48; and a VL comprising the amino acid sequence of SEQ ID NO:63 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:63.
  • the IgG1 is a human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77.
  • a full-length anti-LIGHT antibody comprising an IgG1 constant region comprising: a VH comprising the amino acid sequence of SEQ ID NO:49 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:49; and a VL comprising the amino acid sequence of SEQ ID NO:63 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:63.
  • the IgG1 is a human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77.
  • a full-length anti-LIGHT antibody comprising an IgG1 constant region comprising: a VH comprising the amino acid sequence of SEQ ID NO:50 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:50; and a VL comprising the amino acid sequence of SEQ ID NO:63 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:63.
  • the IgG1 is a human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77.
  • a full-length anti-LIGHT antibody comprising an IgG1 constant region comprising: a VH comprising an amino acid sequence of SEQ ID NO: 47 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 47; and a VL comprising an amino acid sequence of SEQ ID NO: 64 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:
  • the IgG1 is a human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:74.
  • the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO:76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO:77. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:74 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO:76. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:74 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO:77.
  • a full-length anti-LIGHT antibody comprising an IgG1 constant region comprising: a VH comprising the amino acid sequence of SEQ ID NO:48 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:48; and a VL comprising the amino acid sequence of SEQ ID NO:64 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:64.
  • the IgG1 is a human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77.
  • a full-length anti-LIGHT antibody comprising an IgG1 constant region comprising: a VH comprising the amino acid sequence of SEQ ID NO:49 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:49; and a VL comprising the amino acid sequence of SEQ ID NO:64 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:64.
  • the IgG1 is a human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77.
  • a full-length anti-LIGHT antibody comprising an IgG1 constant region comprising: a VH comprising the amino acid sequence of SEQ ID NO:50 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:50; and a VL comprising the amino acid sequence of SEQ ID NO:64 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:64.
  • the IgG1 is a human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77.
  • a full-length anti-LIGHT antibody comprising an IgG1 constant region comprising: a VH comprising the amino acid sequence of SEQ ID NO:47 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:47; and a VL comprising the amino acid sequence of SEQ ID NO:65 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:65.
  • the IgG1 is a human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77.
  • a full-length anti-LIGHT antibody comprising an IgG1 constant region comprising: a VH comprising the amino acid sequence of SEQ ID NO:48 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:48; and a VL comprising the amino acid sequence of SEQ ID NO:65 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:65.
  • the IgG1 is a human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77.
  • a full-length anti-LIGHT antibody comprising an IgG1 constant region comprising: a VH comprising the amino acid sequence of SEQ ID NO:49 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:49; and a VL comprising the amino acid sequence of SEQ ID NO:65 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:65.
  • the IgG1 is a human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77.
  • a full length anti-LIGHT antibody comprising an IgG1 constant region comprising: a VH comprising the amino acid sequence of SEQ ID NO:50 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:50; and a VL comprising the amino acid sequence of SEQ ID NO:65 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:65.
  • the IgG1 is a human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74 and The light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 76. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 77.
  • a full-length anti-LIGHT antibody comprising an IgG1 constant region comprising: a VH comprising an amino acid sequence of SEQ ID NO:51 or a variant thereof having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:51; and a VL comprising an amino acid sequence of SEQ ID NO:63 or a variant thereof having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:63.
  • the IgG1 is a human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77.
  • a full-length anti-LIGHT antibody comprising an IgG1 constant region comprising: a VH comprising the amino acid sequence of SEQ ID NO:52 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:52; and a VL comprising the amino acid sequence of SEQ ID NO:65 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:65.
  • the IgG1 is a human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77.
  • a full-length anti-LIGHT antibody comprising an IgG1 constant region comprising: a VH comprising the amino acid sequence of SEQ ID NO:53 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:53; and a VL comprising the amino acid sequence of SEQ ID NO:65 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:65.
  • the IgG1 is a human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77.
  • a full-length anti-LIGHT antibody comprising an IgG1 constant region comprising: a VH comprising the amino acid sequence of SEQ ID NO:51 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:51; and a VL comprising the amino acid sequence of SEQ ID NO:65 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:65.
  • the IgG1 is human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 76. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 77. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 77.
  • a full-length anti-LIGHT antibody comprising an IgG1 constant region comprising: a VH comprising the amino acid sequence of SEQ ID NO:54 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:54; and a VL comprising the amino acid sequence of SEQ ID NO:66 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:66.
  • the IgG1 is a human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77.
  • a full-length anti-LIGHT antibody comprising an IgG1 constant region comprising: a VH comprising the amino acid sequence of SEQ ID NO:55 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:55; and a VL comprising the amino acid sequence of SEQ ID NO:67 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:67.
  • the IgG1 is a human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77.
  • a full-length anti-LIGHT antibody comprising an IgG1 constant region comprising: a VH comprising the amino acid sequence of SEQ ID NO:56 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:56; and a VL comprising the amino acid sequence of SEQ ID NO:68 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:68.
  • the IgG1 is a human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77.
  • a full-length anti-LIGHT antibody comprising an IgG1 constant region comprising: a VH comprising an amino acid sequence of SEQ ID NO: 57 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 57; and a VL comprising an amino acid sequence of SEQ ID NO: 69 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:
  • the IgG1 is a human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:74.
  • the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO:76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO:77. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:74 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO:76. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:74 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO:77.
  • a full-length anti-LIGHT antibody comprising an IgG1 constant region comprising: a VH comprising the amino acid sequence of SEQ ID NO:58 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:58; and a VL comprising the amino acid sequence of SEQ ID NO:70 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:70.
  • the IgG1 is a human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77.
  • a full-length anti-LIGHT antibody comprising an IgG1 constant region comprising: a VH comprising the amino acid sequence of SEQ ID NO:59 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:59; and a VL comprising the amino acid sequence of SEQ ID NO:71 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:71.
  • the IgG1 is a human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77.
  • a full-length anti-LIGHT antibody comprising an IgG1 constant region comprising: a VH comprising the amino acid sequence of SEQ ID NO:60 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:60; and a VL comprising the amino acid sequence of SEQ ID NO:72 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:72.
  • the IgG1 is a human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77.
  • a full-length anti-LIGHT antibody comprising an IgG1 constant region comprising: a VH comprising the amino acid sequence of SEQ ID NO:84 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:84; and a VL comprising the amino acid sequence of SEQ ID NO:86 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:86.
  • the IgG1 is a human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77.
  • a full-length anti-LIGHT antibody comprising an IgG1 constant region comprising: a VH comprising the amino acid sequence of SEQ ID NO: 85 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 85; and a VL comprising the amino acid sequence of SEQ ID NO: 87 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 87.
  • the IgG1 is a human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 74.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 77. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 76. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 77.
  • a full-length anti-LIGHT antibody comprising an IgG1 constant region comprising: a VH comprising the amino acid sequence of SEQ ID NO: 84 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 84; and a VL comprising the amino acid sequence of SEQ ID NO: 88 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 88.
  • the IgG1 is a human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 74.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 77. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 76. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 77.
  • a full length anti-LIGHT antibody comprising an IgG1 constant region comprising: a VH comprising the amino acid sequence of SEQ ID NO:84 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:84; and a VL comprising the amino acid sequence of SEQ ID NO:89 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:89.
  • the IgG1 is a human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74 and The light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 76. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 77.
  • a full-length anti-LIGHT antibody comprising an IgG1 constant region comprising: a VH comprising the amino acid sequence of SEQ ID NO:85 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:85; and a VL comprising the amino acid sequence of SEQ ID NO:90 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:90.
  • the IgG1 is a human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77.
  • a full-length anti-LIGHT antibody comprising an IgG1 constant region comprising: a VH comprising the amino acid sequence of SEQ ID NO:84 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:84; and a VL comprising the amino acid sequence of SEQ ID NO:91 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:91.
  • the IgG1 is a human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77.
  • a full-length anti-LIGHT antibody comprising an IgG1 constant region comprising: a VH comprising the amino acid sequence of SEQ ID NO:61 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:61; and a VL comprising the amino acid sequence of SEQ ID NO:73 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:73.
  • the IgG1 is a human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77.
  • a full-length anti-LIGHT antibody comprising an IgG1 constant region comprising: a VH comprising the amino acid sequence of SEQ ID NO:92 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:92; and a VL comprising the amino acid sequence of SEQ ID NO:95 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:95.
  • the IgG1 is a human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 76. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 77. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 77.
  • a full-length anti-LIGHT antibody comprising an IgG1 constant region comprising: a VH comprising the amino acid sequence of SEQ ID NO:93 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:93; and a VL comprising the amino acid sequence of SEQ ID NO:96 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:96.
  • the IgG1 is a human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77.
  • a full-length anti-LIGHT antibody comprising an IgG1 constant region comprising: a VH comprising the amino acid sequence of SEQ ID NO:92 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:92; and a VL comprising the amino acid sequence of SEQ ID NO:96 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:96.
  • the IgG1 is a human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77.
  • a full-length anti-LIGHT antibody comprising an IgG1 constant region comprising: a VH comprising the amino acid sequence of SEQ ID NO:94 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:94; and a VL comprising the amino acid sequence of SEQ ID NO:97 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:97.
  • the IgG1 is a human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77.
  • a full-length anti-LIGHT antibody comprising an IgG1 constant region comprising: a VH comprising an amino acid sequence of SEQ ID NO: 94 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 94; and a VL comprising an amino acid sequence of SEQ ID NO: 98 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:
  • the IgG1 is a human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:74.
  • the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO:76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO:77. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:74 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO:76. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:74 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO:77.
  • a full-length anti-LIGHT antibody comprising an IgG1 constant region comprising: a VH comprising the amino acid sequence of SEQ ID NO:93 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:93; and a VL comprising the amino acid sequence of SEQ ID NO:98 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:98.
  • the IgG1 is a human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77.
  • a full-length anti-LIGHT antibody comprising an IgG1 constant region comprising: a VH comprising the amino acid sequence of SEQ ID NO:92 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:92; and a VL comprising the amino acid sequence of SEQ ID NO:98 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:98.
  • the IgG1 is a human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77.
  • a full-length anti-LIGHT antibody comprising an IgG1 constant region comprising: a VH comprising the amino acid sequence of SEQ ID NO:94 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:94; and a VL comprising the amino acid sequence of SEQ ID NO:99 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:99.
  • the IgG1 is a human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77.
  • a full-length anti-LIGHT antibody comprising an IgG1 constant region comprising: a VH comprising the amino acid sequence of SEQ ID NO:92 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:92; and a VL comprising the amino acid sequence of SEQ ID NO:99 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:99.
  • the IgG1 is a human IgG1.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77.
  • a full-length anti-LIGHT antibody comprising an IgG4 constant region comprising: a VH comprising the amino acid sequence of SEQ ID NO:46 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:46; and a VL comprising the amino acid sequence of SEQ ID NO:62 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:62.
  • the IgG4 is a human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77.
  • a full-length anti-LIGHT antibody comprising an IgG4 constant region comprising: a VH comprising the amino acid sequence of SEQ ID NO:47 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:47; and a VL comprising the amino acid sequence of SEQ ID NO:63 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:63.
  • the IgG4 is a human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77.
  • a full length anti-LIGHT antibody comprising an IgG4 constant region comprising: a VH comprising the amino acid sequence of SEQ ID NO:48 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:48; and a VL comprising the amino acid sequence of SEQ ID NO:63 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:63.
  • the IgG4 is a human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75 and The light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 76. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 77.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77.
  • a full-length anti-LIGHT antibody comprising an IgG4 constant region comprising: a VH comprising the amino acid sequence of SEQ ID NO:50 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:50; and a VL comprising the amino acid sequence of SEQ ID NO:63 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:63.
  • the IgG4 is a human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77.
  • a full-length anti-LIGHT antibody comprising an IgG4 constant region comprising: a VH comprising the amino acid sequence of SEQ ID NO:47 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:47; and a VL comprising the amino acid sequence of SEQ ID NO:64 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:64.
  • the IgG4 is a human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77.
  • a full-length anti-LIGHT antibody comprising an IgG4 constant region comprising: a VH comprising the amino acid sequence of SEQ ID NO:48 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:48; and a VL comprising the amino acid sequence of SEQ ID NO:64 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:64.
  • the IgG4 is a human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 76. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 77. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 77.
  • a full-length anti-LIGHT antibody comprising an IgG4 constant region comprising: a VH comprising the amino acid sequence of SEQ ID NO:49 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:49; and a VL comprising the amino acid sequence of SEQ ID NO:64 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:64.
  • the IgG4 is a human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77.
  • a full-length anti-LIGHT antibody comprising an IgG4 constant region comprising: a VH comprising the amino acid sequence of SEQ ID NO:50 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:50; and a VL comprising the amino acid sequence of SEQ ID NO:64 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:64.
  • the IgG4 is a human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77.
  • a full-length anti-LIGHT antibody comprising an IgG4 constant region comprising: a VH comprising the amino acid sequence of SEQ ID NO:47 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:47; and a VL comprising the amino acid sequence of SEQ ID NO:65 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:65.
  • the IgG4 is a human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77.
  • a full-length anti-LIGHT antibody comprising an IgG4 constant region comprising: a VH comprising an amino acid sequence of SEQ ID NO: 48 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 48; and a VL comprising an amino acid sequence of SEQ ID NO: 65 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:
  • the IgG4 is a human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:75.
  • the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO:76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO:77. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:75 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO:76. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:75 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO:77.
  • a full-length anti-LIGHT antibody comprising an IgG4 constant region comprising: a VH comprising the amino acid sequence of SEQ ID NO:49 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:49; and a VL comprising the amino acid sequence of SEQ ID NO:65 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:65.
  • the IgG4 is a human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77.
  • a full-length anti-LIGHT antibody comprising an IgG4 constant region comprising: a VH comprising the amino acid sequence of SEQ ID NO:50 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:50; and a VL comprising the amino acid sequence of SEQ ID NO:65 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:65.
  • the IgG4 is a human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77.
  • a full-length anti-LIGHT antibody comprising an IgG4 constant region comprising: a VH comprising the amino acid sequence of SEQ ID NO:51 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:51; and a VL comprising the amino acid sequence of SEQ ID NO:63 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:63.
  • the IgG4 is a human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77.
  • a full-length anti-LIGHT antibody comprising an IgG4 constant region comprising: a VH comprising the amino acid sequence of SEQ ID NO:52 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:52; and a VL comprising the amino acid sequence of SEQ ID NO:65 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:65.
  • the IgG4 is a human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77.
  • a full-length anti-LIGHT antibody comprising an IgG4 constant region comprising: a VH comprising the amino acid sequence of SEQ ID NO:53 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:53; and a VL comprising the amino acid sequence of SEQ ID NO:65 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:65.
  • the IgG4 is a human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77.
  • a full-length anti-LIGHT antibody comprising an IgG4 constant region comprising: a VH comprising the amino acid sequence of SEQ ID NO:51 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:51; and a VL comprising the amino acid sequence of SEQ ID NO:65 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:65.
  • the IgG4 is a human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77.
  • a full length anti-LIGHT antibody comprising an IgG4 constant region comprising: a VH comprising the amino acid sequence of SEQ ID NO:54 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:54; and a VL comprising the amino acid sequence of SEQ ID NO:66 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:66.
  • the IgG4 is a human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75 and The light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 76. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 77.
  • a full-length anti-LIGHT antibody comprising an IgG4 constant region comprising: a VH comprising the amino acid sequence of SEQ ID NO:55 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:55; and a VL comprising the amino acid sequence of SEQ ID NO:67 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:67.
  • the IgG4 is a human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77.
  • a full-length anti-LIGHT antibody comprising an IgG4 constant region comprising: a VH comprising the amino acid sequence of SEQ ID NO:56 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:56; and a VL comprising the amino acid sequence of SEQ ID NO:68 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:68.
  • the IgG4 is a human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77.
  • a full-length anti-LIGHT antibody comprising an IgG4 constant region comprising: a VH comprising the amino acid sequence of SEQ ID NO:57 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:57; and a VL comprising the amino acid sequence of SEQ ID NO:69 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:69.
  • the IgG4 is a human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77.
  • a full-length anti-LIGHT antibody comprising an IgG4 constant region comprising: a VH comprising the amino acid sequence of SEQ ID NO:58 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:58; and a VL comprising the amino acid sequence of SEQ ID NO:70 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:70.
  • the IgG4 is a human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 76. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 77. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 77.
  • a full-length anti-LIGHT antibody comprising an IgG4 constant region comprising: a VH comprising the amino acid sequence of SEQ ID NO:59 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:59; and a VL comprising the amino acid sequence of SEQ ID NO:71 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:71.
  • the IgG4 is a human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77.
  • a full-length anti-LIGHT antibody comprising an IgG4 constant region comprising: a VH comprising the amino acid sequence of SEQ ID NO:60 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:60; and a VL comprising the amino acid sequence of SEQ ID NO:72 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:72.
  • the IgG4 is a human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77.
  • a full-length anti-LIGHT antibody comprising an IgG4 constant region comprising: a VH comprising the amino acid sequence of SEQ ID NO:84 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:84; and a VL comprising the amino acid sequence of SEQ ID NO:86 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:86.
  • the IgG4 is a human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77.
  • a full-length anti-LIGHT antibody comprising an IgG4 constant region comprising: a VH comprising an amino acid sequence of SEQ ID NO: 85 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 85; and a VL comprising an amino acid sequence of SEQ ID NO: 87 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:
  • the IgG4 is a human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:75.
  • the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO:76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO:77. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:75 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO:76. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:75 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO:77.
  • a full-length anti-LIGHT antibody comprising an IgG4 constant region comprising: a VH comprising the amino acid sequence of SEQ ID NO:84 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:84; and a VL comprising the amino acid sequence of SEQ ID NO:88 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:88.
  • the IgG4 is a human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77.
  • a full-length anti-LIGHT antibody comprising an IgG4 constant region comprising: a VH comprising the amino acid sequence of SEQ ID NO:84 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:84; and a VL comprising the amino acid sequence of SEQ ID NO:89 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:89.
  • the IgG4 is a human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77.
  • a full length anti-LIGHT antibody comprising an IgG4 constant region comprising: a VH comprising the amino acid sequence of SEQ ID NO:85 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:85; and a VL comprising the amino acid sequence of SEQ ID NO:90 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:90.
  • the IgG4 is a human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77.
  • a full-length anti-LIGHT antibody comprising an IgG4 constant region comprising: a VH comprising the amino acid sequence of SEQ ID NO:84 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:84; and a VL comprising the amino acid sequence of SEQ ID NO:91 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:91.
  • the IgG4 is a human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77.
  • a full-length anti-LIGHT antibody comprising an IgG4 constant region comprising: a VH comprising the amino acid sequence of SEQ ID NO:61 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:61; and a VL comprising the amino acid sequence of SEQ ID NO:73 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:73.
  • the IgG4 is a human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77.
  • a full-length anti-LIGHT antibody comprising an IgG4 constant region comprising: a VH comprising the amino acid sequence of SEQ ID NO:92 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:92; and a VL comprising the amino acid sequence of SEQ ID NO:95 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:95.
  • the IgG4 is a human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77.
  • a full length anti-LIGHT antibody comprising an IgG4 constant region comprising: a VH comprising the amino acid sequence of SEQ ID NO:93 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:93; and a VL comprising the amino acid sequence of SEQ ID NO:96 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:96.
  • the IgG4 is a human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75 and The light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 76. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 77.
  • a full-length anti-LIGHT antibody comprising an IgG4 constant region comprising: a VH comprising the amino acid sequence of SEQ ID NO:92 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:92; and a VL comprising the amino acid sequence of SEQ ID NO:96 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:96.
  • the IgG4 is a human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77.
  • a full-length anti-LIGHT antibody comprising an IgG4 constant region comprising: a VH comprising the amino acid sequence of SEQ ID NO:94 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:94; and a VL comprising the amino acid sequence of SEQ ID NO:97 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:97.
  • the IgG4 is a human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77.
  • a full-length anti-LIGHT antibody comprising an IgG4 constant region comprising: a VH comprising the amino acid sequence of SEQ ID NO:94 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:94; and a VL comprising the amino acid sequence of SEQ ID NO:98 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:98.
  • the IgG4 is a human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77.
  • a full-length anti-LIGHT antibody comprising an IgG4 constant region comprising: a VH comprising the amino acid sequence of SEQ ID NO: 93 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 93; and a VL comprising the amino acid sequence of SEQ ID NO: 98 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 98.
  • the IgG4 is a human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 75.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 76. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 77. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 77.
  • a full-length anti-LIGHT antibody comprising an IgG4 constant region comprising: a VH comprising the amino acid sequence of SEQ ID NO:92 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:92; and a VL comprising the amino acid sequence of SEQ ID NO:98 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:98.
  • the IgG4 is a human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77.
  • a full-length anti-LIGHT antibody comprising an IgG4 constant region comprising: a VH comprising the amino acid sequence of SEQ ID NO:94 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:94; and a VL comprising the amino acid sequence of SEQ ID NO:99 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:99.
  • the IgG4 is a human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77.
  • a full length anti-LIGHT antibody comprising an IgG4 constant region comprising: a VH comprising the amino acid sequence of SEQ ID NO:92 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:92; and a VL comprising the amino acid sequence of SEQ ID NO:99 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:99.
  • the IgG4 is a human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77.
  • Binding affinity is expressed as Kd, Koff, Kon or Ka.
  • Koff refers to the rate constant for the dissociation of an antibody from an antigen/antibody complex, as measured by a kinetic selection apparatus.
  • Kon refers to the rate constant for the dissociation of an antibody from an antigen/antibody complex, as measured by a kinetic selection apparatus.
  • the equilibrium dissociation constant Kd used in this article refers to the dissociation constant when a specific antibody-antigen interacts, which refers to the antigen concentration required when the antigen occupies half of all antibody binding sites and reaches equilibrium in the antibody molecule solution, equal to Koff/Kon. The determination of Kd assumes that all binding molecules are in solution.
  • the corresponding equilibrium dissociation rate constant is expressed using EC50 , which is a good approximation of Kd.
  • the affinity binding constant Ka is the reciprocal of the dissociation constant Kd.
  • the dissociation constant (Kd) can be used as an indicator of the affinity of the reactive antibody moiety to the antigen.
  • Kd dissociation constant
  • a simple analysis can be performed using antibodies labeled with various markers by the Scatchard method and a Biacore instrument (manufactured by Amersham Biosciences), and the interaction between biomolecules can be analyzed by surface plasmon resonance according to the user manual or the accompanying kit.
  • the Kd values obtained using these methods are expressed in units of M.
  • Antibodies that specifically bind to a target may have, for example, a Kd value of ⁇ 10 -7 M, ⁇ 10 -8 M, ⁇ 10 -9 M, ⁇ 10 -10 M, ⁇ 10 -11 M, ⁇ 10 -12 M, or ⁇ 10 -13 M.
  • the binding specificity of an antibody can be experimentally determined by methods known in the art. These methods include, but are not limited to, Western blots, ELISA-, RIA-, ECL-, IRMA-, EIA-, BIAcore assays, and peptide scanning, among others.
  • the anti-LIGHT antibody specifically binds to the LIGHT target with a Kd value of 10-7 M to 10-13 M (eg, 10-7 M to 10-13 M, 10-8 M to 10-13 M, 10-9 M to 10-13 M, or 10-10 M to 10-12 M).
  • the Kd value for binding between an anti-LIGHT antibody and LIGHT is 10 -7 M to 10 -13 M, 1 ⁇ 10 -7 M to 5 ⁇ 10 - 13 M, 10 -7 M to 10 -12 M, 10 -7 M to 10 -11 M, 10 -7 M to 10 -10 M, 10 -7 M to 10 -9 M, 10 -8 M to 10 -13 M , 1 ⁇ 10 -8 M to 5 ⁇ 10 -13 M, 10 -8 M to 10 -12 M, 10 -8 M to 10 -11 M, 10 -8 M to 10 -10 M, 10 -8 M to 10 -9 M, 5 ⁇ 10 -9 M to 1 ⁇ 10 -13 M, 5 ⁇ 10 -9 M to 1 ⁇ 10 -12 M, 5 ⁇ 10 -9 M to 1 ⁇ 10 -11 M, 5 ⁇ 10 -9 M to 1 ⁇ 10 -10 1 ⁇ 10 -10 M to 5 ⁇ 10 -13 M, 1 ⁇ 10 -10 M to 1 ⁇ 10 -12 M, 1 ⁇ 10 -10 M to 1 ⁇ 10 -12
  • the Kd value of the combination between the anti-LIGHT antibody and the non-target is higher than the Kd value of the anti-LIGHT antibody and the target, and in some embodiments cited herein, the binding affinity of the anti-LIGHT antibody to the target (e.g., LIGHT) is higher than the binding affinity of the anti-LIGHT antibody to the non-target.
  • the non-target refers to an antigen that is not LIGHT.
  • the Kd value of the combination of the anti-LIGHT antibody (for LIGHT) and the non-LIGHT target differs by at least 10 times, for example, 10-100 times, 100-1000 times, 10 3 -10 4 times, 10 4 -10 5 times, 10 5 -10 6 times, 10 6 -10 7 times, 10 7 -10 8 times, 10 8 -10 9 times, 10 9 -10 10 times, 10 10 -10 11 times, 10 11 -10 12 times.
  • the Kd value of the anti-LIGHT antibody binding to a non-target is 10 -1 M to 10 -6 M (e.g., 10 -1 M to 10 -6 M, 10 -1 M to 10 -5 M, 10 -2 M to 10 -4 M).
  • the non-target refers to an antigen other than LIGHT.
  • the Kd value of the binding between the anti-LIGHT antibody and a non-LIGHT target is 10 -1 M to 10 -6 M, 1 ⁇ 10 -1 M to 5 ⁇ 10 -6 M, 10 -1 M to 10 -5 M, 1 ⁇ 10 -1 M to 5 ⁇ 10 -5 M, 10 -1 M to 10 -4 M, 1 ⁇ 10 -1 M to 5 ⁇ 10 -4 M, 10 -1 M to 10 -3 M, 1 ⁇ 10 -1 M to 5 ⁇ 10 -3 M, 10 -1 M to 10 -2 M, 10 -2 M to 10 -6 M, 1 ⁇ 10 -2 M -6 M, 10 -2 M to 10 -5 M, 1 ⁇ 10 -2 M to 5 ⁇ 10 -5 M, 10 -2 M to 10 -4 M, 1 ⁇ 10 -2 M to 5 ⁇ 10 -4 M, 10 -2 M to 10 -3 M, 10 -3 M to 10 -6 M , 1 ⁇ 10 -3 M to 5 ⁇ 10 -6 M, 10 -3 M, 10 -3 M to 10 -6 M, 1
  • an anti-LIGHT antibody specifically recognizes a LIGHT target with high binding affinity, and binds to a non-target with low binding affinity
  • the anti-LIGHT antibody binds to the LIGHT target with a Kd value of 10-7 M to 10-13 M (e.g., 10-7 M to 10-13 M, 10-8 M to 10-13 M, 10-9 M to 10-13 M, 10-10 M to 10-12 M), and binds to a non-target with a Kd value of 10-1 M to 10-6 M (e.g., 10-1 M to 10-6 M, 10-1 M to 10-5 M, 10-2 M to 10-4 M).
  • the binding affinity of the anti-LIGHT antibody is compared with the binding affinity of a control anti-LIGHT antibody (e.g., CERC-002).
  • a control anti-LIGHT antibody e.g., CERC-002
  • the Kd value for binding between a control anti-LIGHT antibody and LIGHT can be at least 2 times, e.g., 2 times, 3 times, 4 times, 5 times, 6 times, 7 times, 8 times, 9 times, 10 times, 10-100 times, 100-1000 times, 10 3 -10 4 times, of the Kd value for binding between an anti-LIGHT antibody described herein and LIGHT.
  • nucleic acid molecules encoding anti-LIGHT antibodies are also contemplated.
  • a nucleic acid (or a group of nucleic acids) encoding a full-length anti-LIGHT antibody is provided, including any full-length anti-LIGHT antibody described herein.
  • the nucleic acid (or a group of nucleic acids) of the anti-LIGHT antibody described herein may also include a nucleic acid sequence encoding a polypeptide tag (e.g., a protein purification tag, a His tag, an HA tag).
  • isolated host cells comprising an anti-LIGHT antibody, isolated nucleic acids encoding an anti-LIGHT antibody polypeptide component, or vectors comprising nucleic acids encoding an anti-LIGHT antibody polypeptide component as described herein.
  • the present application also includes variants of these nucleic acid sequences.
  • the variant includes a nucleotide sequence that hybridizes with the nucleic acid sequence encoding the anti-LIGHT antibody of the present application under at least moderately stringent hybridization conditions.
  • the present application also provides a vector into which the nucleic acid sequence of the present application can be inserted.
  • a natural or synthetic nucleic acid encoding an anti-LIGHT antibody is inserted into a suitable expression vector so that the nucleic acid is operably linked to 5' and 3' end regulatory elements, such as a promoter (e.g., a lymphocyte-specific promoter) and a 3' untranslated region (UTR), and an anti-LIGHT antibody (e.g., a full-length anti-LIGHT antibody) can be expressed.
  • the vector may be suitable for replication and integration in eukaryotic host cells.
  • Typical cloning and expression vectors include transcription and translation terminators, initiation sequences, and promoters that regulate the expression of the target nucleic acid sequence.
  • nucleic acids described herein can also be used for nucleic acid immunization and gene therapy by using standard gene delivery protocols.
  • Nucleic acid delivery methods are known in the art. For example, see U.S. Pat. Nos. 5,399,346, 5,580,859, 5,589,466, which are incorporated herein by reference in their entirety.
  • the present application also provides gene therapy vectors.
  • Nucleic acids can be cloned into many types of vectors.
  • nucleic acids can be cloned into vectors including, but not limited to, plasmids, phagemids, phage derivatives, animal viruses, and cosmids.
  • Vectors of particular interest include expression vectors, replication vectors, probe generation vectors, and sequencing vectors.
  • the expression vector can be provided to the cell in the form of a viral vector.
  • Viral vector technology is well known in the art and is described in, for example, Green and Sambrook (2013, Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratory, New York), and other virology or molecular biology manuals.
  • Viruses that can be used as vectors include, but are not limited to, retroviruses, adenoviruses, adeno-associated viruses, herpes viruses, and lentiviruses.
  • a suitable vector includes a replication origin that works in at least one organism, a promoter sequence, a convenient restriction endonuclease site, and one or more selection markers (see, for example, WO 01/96584; WO 01/29058; and U.S. Pat. No. 6,326,193).
  • retroviruses provide a convenient platform for gene delivery systems.
  • the selected gene can be inserted into a vector and packaged in retroviral particles using techniques known in the art.
  • the recombinant virus is then isolated and delivered to the cells of the subject in vivo or in vitro.
  • Many retroviral systems are known in the art.
  • adenoviral vectors are used.
  • Many adenoviral vectors are known in the art.
  • lentiviral vectors are used.
  • Vectors derived from retroviruses, such as lentiviruses are suitable tools for achieving long-term gene transfer because they allow long-term stable integration of transgenes and reproduction in daughter cells.
  • Lentiviral vectors have additional advantages over retroviruses derived from tumors, such as mouse leukemia viruses, because they can transduce non-dividing cells, such as hepatocytes. At the same time, it also has the additional advantage of low immunogenicity.
  • promoter elements such as enhancers, regulate the frequency of transcription initiation. They are usually located 30-110 bp upstream of the start site, although recently it has been discovered that many promoters also contain functional elements downstream of the start site.
  • the spacing between promoter elements is usually flexible, so that the promoter function is maintained when the elements are interchanged or moved relative to each other.
  • tk thymidine kinase
  • a suitable promoter is the immediate early cytomegalovirus (CMV) promoter sequence. This promoter sequence is a very strong constitutive promoter sequence that can drive any polynucleotide sequence operably linked to it to high levels of expression.
  • CMV immediate early cytomegalovirus
  • EF-1 ⁇ elongation factor 1 ⁇
  • constitutive promoters may also be used, including but not limited to the simian virus 40 (SV40) early promoter, mouse mammary tumor virus (MMTV), human immunodeficiency virus long terminal repeat (HIV-LTR) promoter, MoMuLV promoter, avian leukosis virus promoter, Epstein-Barr virus immediate early promoter, Rous sarcoma virus promoter, and human gene promoters, such as but not limited to actin promoter, myosin promoter, hemoglobin promoter, and creatine kinase promoter.
  • SV40 simian virus 40
  • MMTV mouse mammary tumor virus
  • HV-LTR human immunodeficiency virus long terminal repeat
  • MoMuLV promoter avian leukosis virus promoter
  • Epstein-Barr virus immediate early promoter Epstein-Barr virus immediate early promoter
  • Rous sarcoma virus promoter Rous sarcoma virus promoter
  • human gene promoters such as but not
  • an inducible promoter provides a molecular switch that can start the expression of a polynucleotide sequence operably linked to it when such expression is needed, and turn off expression when it is not needed.
  • Inducible promoters include, but are not limited to, metallothionein promoters, glucocorticoid promoters, progesterone promoters, and tetracycline promoters.
  • expression of the anti-LIGHT antibody is inducible.
  • the nucleic acid sequence encoding the anti-LIGHT antibody is operably linked to an inducible promoter, including any inducible promoter described herein.
  • an inducible promoter provides a molecular switch that can turn on the expression of a polynucleotide sequence operably linked thereto when expression is desired, and turn off expression when expression is not desired.
  • exemplary inducible promoters suitable for use in eukaryotic cells include, But not limited to, hormone regulatory elements (for example, see Mader, S. and White, JH (1993) Proc. Natl. Acad. Sci. USA 90: 5603-5607), synthetic ligand regulatory elements (see Spencer, DM et al (1993) Science 262: 1019-1024) and ionizing radiation regulatory elements (see Manome, Y. et al (1993) Biochemistry 32: 10607-10613; Datta, R.
  • the inducible promoter system used to express anti-LIGHT antibodies is the Tet system.
  • the inducible promoter system used to express the anti-LIGHT antibody is the E. coli lac repression system.
  • an exemplary inducible promoter system used in the present application is the Tet system.
  • the system is based on the Tet system described by Gossen et al. (1993).
  • the target polynucleotide is controlled by a promoter comprising one or more Tet operator (TetO) sites.
  • TetO Tet operator
  • TetR Tet repressor
  • the activated state for example, in the presence of an inducer such as tetracycline (Tc), anhydrotetracycline, doxycycline (Dox) or its active analogs, the inducer releases TetR from TetO, thereby causing transcription to occur.
  • an inducer such as tetracycline (Tc), anhydrotetracycline, doxycycline (Dox) or its active analogs
  • Tc tetracycline
  • Dox doxycycline
  • Doxycycline is a member of the tetracycline antibiotic family, and its chemical name is 1-dimethylamino-2,4a,5,7-pentahydroxy-11-methyl-4,6-dioxy-1,4a,11,11a,12,12a-hexahydrotetraene-3-carboxamide.
  • TetR is codon optimized for expression in mammalian cells, such as mice or human cells. Due to the degeneracy of the genetic code, most amino acids are encoded by more than one codon, so that the sequence of a given nucleic acid has a large number of variants, and the amino acid sequence encoded by it does not change at all. However, many organisms have differences in codon usage, also known as "codon preference" (i.e., the preference for using specific codons for a given amino acid). Codon preference is generally related to the presence of a dominant tRNA species for a specific codon, which in turn improves the efficiency of mRNA translation. Therefore, coding sequences derived from specific species (e.g., prokaryotes) can be customized by codon optimization to improve their expression in different species (e.g., eukaryotes).
  • specific species e.g., prokaryotes
  • Tet-Off transcription is inactivated in the presence of Tc or Dox.
  • a tetracycline-regulated transcription activator protein (tTA) which is composed of a fusion of TetR and the strong transcription activation domain of herpes simplex virus VP16, regulates the expression of the target nucleic acid under the transcriptional control of a tetracycline-responsive promoter element (TRE).
  • the TRE element consists of a fusion of the TetO sequence in series with a promoter (usually a minimal promoter sequence derived from the immediate early promoter of human cytomegalovirus).
  • Tc or Dox binds to TRE and activates transcription of the target gene.
  • tTA cannot bind to TRE and the target gene cannot be expressed.
  • rtTA is a fusion protein consisting of the TetR repressor and the VP16 transcription activation domain.
  • rtTA changes in four amino acids in the DNA binding region of TetR alter the binding properties of rtTA, allowing it to only recognize the tetO sequence on the target transgene TRE in the presence of Dox. Therefore, in the Tet-On system, rtTA can only activate the transcription of the target gene regulated by the TRE in the presence of Dox.
  • lac repressor system of Escherichia coli (see Brown et al., Cell 49:603-612 (1987)).
  • the lac repressor system regulates the expression of a target gene operably linked to a promoter containing the lac operator (lacO).
  • lacO lac operator
  • the transcription of the target polynucleotide functions.
  • lacR lac repressor
  • lacR binds to LacO, thereby preventing the transcription of the target polynucleotide.
  • the expression of the target polynucleotide is induced by a suitable inducer, for example, isopropyl- ⁇ -D-thiogalactopyranoside (IPTG).
  • IPTG isopropyl- ⁇ -D-thiogalactopyranoside
  • the expression vector to be introduced into the cell may also contain a selectable marker gene or a reporter gene or both, so as to identify and select expressing cells from a cell population transfected or infected by a viral vector.
  • the selectable marker may be carried on a separate DNA fragment and used in a co-transfection experiment.
  • Either the selectable marker gene or the reporter gene may be flanked by a suitable regulatory sequence to enable expression in the host cell.
  • Useful selectable markers include, for example, antibiotic resistance genes, such as neo and similar genes.
  • Reporter genes can be used to identify potential transfected cells and evaluate the function of regulatory sequences.
  • a reporter gene is a gene that is not present in or expressed by a recipient organism or tissue, and that encodes a polypeptide whose expression is expressed as some easily detectable properties, such as enzyme activity. After the DNA is introduced into the recipient cell, the expression of the reporter gene is detected at an appropriate time.
  • Suitable reporter genes may include genes encoding luciferase, ⁇ -galactosidase, chloramphenicol acetyltransferase, secreted alkaline phosphatase, or green fluorescent protein (see, Ui-Tel et al., 2000 FEBS Letters 479: 79-82).
  • Suitable expression systems are well known and can be prepared by known techniques or obtained commercially.
  • the construct of the minimum 5' flanking region that can show the highest expression level of the reporter gene is identified as a promoter.
  • a promoter region can be connected to a reporter gene and used to evaluate the ability of certain substances to regulate promoter-driven transcription.
  • nucleic acids encoding any of the full-length anti-LIGHT antibodies described herein are provided.
  • the nucleic acid includes one or more nucleic acid sequences encoding full-length anti-LIGHT antibody heavy chains and light chains.
  • each of the one or more nucleic acid sequences is contained in a separate vector.
  • at least some nucleic acid sequences are contained in the same vector.
  • all nucleic acid sequences are contained in the same vector.
  • the vector can be selected from, for example, mammalian expression vectors and viral vectors (such as vectors derived from retroviruses, adenoviruses, adeno-associated viruses, herpes viruses, and lentiviruses).
  • the vectors can be easily introduced into host cells, such as mammalian cells, bacteria, yeast or insect cells, by any method in the art.
  • the expression vector can be introduced into the host cell by physical, chemical or biological methods.
  • polynucleotides are introduced into host cells by calcium phosphate transfection.
  • Biological methods for introducing target polynucleotides into host cells include the use of DNA and RNA vectors.
  • Viral vectors particularly retroviral vectors, have become the most widely used methods for inserting genes into mammalian cells, such as human cells.
  • Other viral vectors can be derived from lentiviruses, poxviruses, herpes simplex virus type 1, adenoviruses, and adeno-associated viruses, etc. See, e.g., US Pat. Nos. 5,350,674 and 5,585,362.
  • Chemical methods for introducing polynucleotides into host cells include colloidal dispersion systems, such as polymer complexes, nanocapsules, microspheres, magnetic beads, and lipid-based systems, including oil-in-water emulsions, micelles, mixed micelles, and liposomes.
  • colloidal dispersion systems such as polymer complexes, nanocapsules, microspheres, magnetic beads, and lipid-based systems, including oil-in-water emulsions, micelles, mixed micelles, and liposomes.
  • An exemplary colloidal system used as a delivery vehicle in vivo and in vitro is a liposome (e.g., an artificial membrane vesicle).
  • an exemplary delivery vehicle is a liposome. It is contemplated that a lipid formulation is used to introduce nucleic acid into a host cell (in vitro, in vitro or in vivo). On the other hand, the nucleic acid can be combined with a lipid.
  • Nucleic acids combined with lipids can be wrapped into the aqueous interior of the liposome, dispersed in the lipid bilayer of the liposome, connected to the liposome by a linker molecule combined with the liposome and the oligonucleotide, embedded in the liposome, forming a complex with the liposome, dispersed in a solution containing lipids, mixed with lipids, combined with lipids, suspended in lipids, contained in micelles or mixed with micelles, or otherwise combined with lipids.
  • Lipid, lipid/DNA or lipid/expression vector related compositions are not limited to any specific structure in solution. For example, they may exist in a bilayer structure, in micelles or in a "collapsed" structure.
  • Lipids are fatty substances, which can be naturally occurring or synthetic lipids.
  • lipids include fat droplets naturally present in the cytoplasm, and a class of compounds containing long-chain aliphatic hydrocarbons and their derivatives, such as fatty acids, alcohols, amines, amino alcohols and aldehydes.
  • experiments can be performed to confirm that the recombinant DNA sequence is present in the host cell.
  • Such experiments include, for example, "molecular biology” experiments well known to those skilled in the art. For example, Southern and Northern blotting, RT-PCR and PCR; "biochemical” experiments, such as detecting the presence or absence of a particular polypeptide, such as by immunological methods (ELISAs and Western blots) or by the experiments described herein, are all within the scope of the present application.
  • the anti-LIGHT antibody is a monoclonal antibody or is derived from a monoclonal antibody. In some embodiments, the anti-LIGHT antibody comprises VH and VL from a monoclonal antibody, or a variant thereof. In some embodiments, the anti-LIGHT antibody further comprises CH1 and CL regions from a monoclonal antibody, or a variant thereof.
  • Monoclonal antibodies can be prepared using methods known in the art, such as hybridoma cell methods, phage display methods, or using recombinant DNA methods. In addition, exemplary phage display methods are described herein and in the following examples.
  • an immunizing agent is usually used to immunize hamsters, mice or other suitable host animals to induce lymphocytes that produce or are capable of producing antibodies that specifically bind to the immunizing agent.
  • lymphocytes can be immunized in vitro.
  • the immunizing agent may include a polypeptide or fusion protein of the target protein.
  • PBLs peripheral blood lymphocytes
  • spleen cells or lymph node cells are used. Lymphocytes are fused with immortal cell lines using an appropriate fusion agent, such as polyethylene glycol, to form hybridoma cells.
  • Immortal cell lines are typically transformed mammalian cells, especially myeloma cells of rodents, bovines and humans. Rat or mouse myeloma cell lines are typically used.
  • Hybridoma cells can be cultured in a suitable culture medium, and the culture medium preferably contains one or more substances that inhibit the growth or survival of unfused immortal cells.
  • the parental cells lack the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRT or HPRT)
  • the hybridoma cell culture medium typically includes hypoxanthine, aminopterin, and thymidine (HAT medium), which prevents the growth of HGPRT-deficient cells.
  • the immortalized cell line is effectively fused, and the antibody is stably expressed at a high level by the selected antibody production cells, and is sensitive to certain culture media, such as HAT culture media.
  • the immortalized cell line is a mouse myeloma cell line, which can be obtained from, for example, the Salk Cell Collection in San Diego, California and the American Type Culture Collection in Manassas, Virginia. Human myeloma and mouse-human hybrid myeloma cell lines are also described for the preparation of human monoclonal antibodies.
  • the presence of monoclonal antibodies against the polypeptide in the culture medium of the hybridoma cells can then be determined.
  • the binding specificity of the monoclonal antibodies produced by the hybridoma cells can be determined by immunoprecipitation or in vitro binding assays, such as radioimmunoassay (RIA) or enzyme-linked immunosorbent assay (ELISA). Such techniques or analytical methods are known in the art.
  • the binding affinity of the monoclonal antibodies can be determined by, for example, Scatchard analysis as described in Munson and Pollard, Anal. Biochem., 107: 220 (1980).
  • the target clones can be subcloned by limiting dilution and cultured by standard methods. Suitable culture media for this purpose include, for example, modified Eagle medium (DMEM) and RPMI-1640 culture media. Alternatively, hybridoma cells can be grown in mammals in the form of ascites.
  • DMEM modified Eagle medium
  • RPMI-1640 culture media for example, modified Eagle medium (DMEM) and RPMI-1640 culture media.
  • hybridoma cells can be grown in mammals in the form of ascites.
  • the monoclonal antibodies secreted by the subclones can be isolated or purified from the culture medium or ascites fluid by conventional immunoglobulin purification procedures, such as protein A-Sepharose, hydroxylapatite chromatography, gel electrophoresis, dialysis, or affinity chromatography.
  • the anti-LIGHT antibody comprises a sequence selected from a clone of an antibody library (e.g., a phage library displaying scFv or Fab fragments).
  • the clone can be identified by a method for screening a combinatorial library of antibody fragments having the desired activity. For example, various methods are known in the art for generating phage display libraries and screening these libraries to obtain antibodies with the desired binding properties.
  • phage display methods the repertoires of VH and VL genes are cloned separately by polymerase chain reaction (PCR) and randomly recombined in a phage library, and then screened for phage that can bind to the antigen, as described in Winter et al., Ann. Rev. Immunol., 12: 433-455 (1994). Phages typically display antibody fragments in the form of scFv fragments or Fab fragments. Library phages of immune origin provide high-affinity antibodies against immunogens without the need to construct hybridoma cells.
  • PCR polymerase chain reaction
  • natural libraries can be cloned to provide a single source of antibodies against a variety of non-self antigens and self antigens without any immunization, as described in Griffiths et al., EMBO J, 12: 725-734 (1993).
  • natural libraries can also be prepared by cloning non-rearranged V-gene fragments from stem cells and using PCR primers containing random sequences encoding the CDR3 hypervariable regions and performing rearrangement in vitro, as described in Hoogenboom and Winter, J. Mol. Biol., 227:381-388 (1992).
  • Patent publications describing human antibody phage libraries include, for example, US Pat. No. 5,750,373 and US Patent Publication Nos. 2005/0079574, 2005/0119455, 2005/0266000, 2007/0117126, 2007/0160598, 2007/0237764, 2007/0292936, and 2009/0002360.
  • the anti-LIGHT antibody is prepared by a method of screening the anti-LIGHT antibody part in the library that can specifically bind to the target LIGHT through phage display.
  • the library can be a human scFv phage display library, having at least 1 ⁇ 10 9 (e.g., at least 1 ⁇ 10 9 , 2.5 ⁇ 10 9 , 5 ⁇ 10 9 , 7.5 ⁇ 10 9 , 1 ⁇ 10 10 , 2.5 ⁇ 10 10 , 5 ⁇ 10 10 , 7.5 ⁇ 10 10 or 1 ⁇ 10 11 ) species of diversity of unique human antibody fragments.
  • the library is a human natural library, constructed by DNA extracted from PMBCs and spleens of healthy subjects, comprising all human heavy and light chain subfamilies.
  • the library is a human natural library, constructed by DNA extracted from PMBCs isolated from patients with various diseases, such as patients with autoimmune diseases, cancer patients, and patients with infectious diseases.
  • the library is a semisynthetic human library, wherein the heavy chain CDR3 is completely random, and all amino acids (except cysteine) are present at any given position with the same probability. (See, e.g., Hoet, RMet al., Nat. Biotechnol. 23 (3): 344-348, 2005).
  • the heavy chain CDR3 length of the semisynthetic human library is between 5 and 24 (e.g., 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 or 24) amino acids.
  • the library is a fully synthetic phage display library.
  • the library is a non-human phage display library.
  • Phage clones with high affinity to the target LIGHT can be screened by iterative binding of phage to the target LIGHT, which is bound to a solid support (e.g., beads for solution panning or mammalian cells for cell panning), followed by removal of unbound phage and elution of specifically bound phage. Subsequently, the bound phage clones are eluted and used to infect suitable host cells, such as E. coli XL1-Blue, for expression and purification.
  • Phage clones that specifically bind to LIGHT can be enriched by multiple rounds of panning (e.g., 2, 3, 4, 5, 6 or more rounds), such as solution panning, cell panning, or a combination of both.
  • the specific binding of the enriched phage clones to the target LIGHT can be detected by any method known in the art, including, for example, ELISA and FACS.
  • Another method for screening antibody libraries is to display proteins on the surface of yeast cells.
  • Wittrup et al. U.S. Pat. Nos. 6,699,658 and 6,696,251 developed a method for displaying libraries in yeast cells.
  • one component includes a yeast lectin protein (Aga1) anchored on the yeast cell wall, and another component includes the second subunit of the lectin protein Aga2, which can bind to the Aga1 protein through a disulfide bond and then be displayed on the yeast cell surface.
  • the Aga1 protein is expressed by integrating the Aga1 gene into the yeast chromosome.
  • the single-chain variable fragment (scFv) library is fused to the Aga2 gene in the yeast display plasmid, and after transformation, the library can be retained in the yeast due to the presence of an additional nutritional marker. Both Aga1 and Aga2 proteins are expressed under the control of a galactose-inducible promoter.
  • the human antibody V gene library ( VH and VK fragments) is obtained by PCR using a set of degenerate primers (Sblattero, D. and Bradbury, A. Immunotechnology 3, 271-278 1998).
  • the PCR templates are from commercially available RNA or cDNA, including PBMC, spleen, lymph nodes, bone marrow and tonsils. After the independent VH and VK PCR libraries are merged, they are assembled into scFv forms by overlap extension PCR (Sheets, MDet al, Proc. Natl. Acad. Sci. USA 95, 6157-6162 1998).
  • yeast scFv display library In order to construct a yeast scFv display library, the resulting scFv PCR product is cloned into a yeast display plasmid in yeast by homologous recombination. (Chao, G, et al, Nat Protoc. 2006; 1(2):755-68. Miller KD, et al. Current Protocols in Cytometry 4.7.1-4.7.30, 2008).
  • Anti-LIGHT antibodies can be screened using a mammalian cell display system, in which the antibody portion is displayed on the cell surface and antibodies that specifically target LIGHT are isolated by an antigen-directed screening method (as described in U.S. patent No. 7,732,195B2).
  • a Chinese hamster ovary (CHO) cell library displaying a large number of human IgG antibody genes can be established and used to discover clones expressing high-affinity antibody genes.
  • Another display system has been developed that allows the same protein to be displayed and secreted on the cell surface at the same time through alternative splicing, in which the displayed protein phenotype remains associated with the genotype, allowing the secreted soluble antibody to be characterized in both biophysical and cell function-based analyses.
  • This method overcomes many of the limitations of previous mammalian cell displays and is capable of directly screening and maturing full-length, glycosylated IgGs in the form of antibodies (Peter M. Bowers, et al, Methods 2014, 65: 44-56).
  • Transient expression systems are suitable for a single round of antigen selection before antibody gene recovery and are therefore most useful for selecting antibodies from smaller libraries.
  • Stable exosome vectors provide an attractive option. Exosome vectors can be efficiently transfected and stably maintained at low copy numbers, allowing multiple rounds of panning and the resolution of more complex antibody repertoires.
  • the IgG library is constructed based on the connection of the germline sequence V gene fragments isolated from a group of human donors and the rearranged (D) J region. RNA collected from 2000 human blood samples was reverse transcribed into cDNA, and the V H and V K fragments were amplified using V H and V K specific primers and purified by gel extraction. The V H and V K fragments were subcloned into display vectors containing IgG1 or K constant regions, respectively, and then electroporated or transduced into 293T cells to prepare the IgG library.
  • V H and V K were connected to produce scFv, which were then subcloned into the display vector and electroporated or transduced into 293T cells.
  • the IgG library is constructed based on the germline sequence V gene fragments isolated from a group of donors and the rearranged (D) J region, and the donors can be mice, rats, rabbits or monkeys.
  • Monoclonal antibodies can also be prepared by recombinant DNA methods, such as those described in U.S. Patent No. 4,816,567.
  • the DNA encoding the monoclonal antibodies described in the present application can be easily isolated and sequenced by conventional methods (e.g., by oligonucleotide probes that can specifically bind to the genes encoding the light and heavy chains of mouse antibodies).
  • the hybridoma cells described above or the LIGHT-specific phage clones of the present application can be used as the source of such DNA.
  • the DNA can be placed in an expression vector, which is then transfected into a host cell, such as a simian COS cell, a Chinese hamster ovary carcinoma (CHO) cell, or a myeloma cell that does not produce immunoglobulins, to obtain a monoclonal antibody synthesized in a recombinant host cell.
  • a host cell such as a simian COS cell, a Chinese hamster ovary carcinoma (CHO) cell, or a myeloma cell that does not produce immunoglobulins.
  • the DNA can also be modified, such as by replacing the human heavy and light chain constant regions with coding sequences and/or replacing homologous non-human sequences with framework regions (U.S. Patent No.
  • the antibody can be a monovalent antibody.
  • Methods for preparing monovalent antibodies are known in the art. For example, a recombinant expression method involving immunoglobulin light chains and modified heavy chains.
  • the heavy chains are usually truncated at any position in the Fc region to prevent the heavy chains from cross-linking with each other.
  • the relevant cysteine residues are replaced by other amino acid residues or are deleted to prevent cross-linking.
  • In vitro methods are also suitable for preparing monovalent antibodies. Digestion of antibodies to produce antibody fragments, particularly Fab fragments, can be accomplished using any method known in the art.
  • the antibody variable domains with the desired binding specificity can be fused to an immunoglobulin constant region.
  • the fusion is performed with an immunoglobulin heavy chain constant region, which includes at least a portion of the hinge, CH2 and CH3 regions.
  • the first heavy chain constant region (CH1) containing the necessary sites for light chain binding is present in at least one fusion.
  • the DNA encoding the immunoglobulin heavy chain fusion if desired, may also include DNA encoding the immunoglobulin light chain, is inserted into an independent expression vector, and co-transfected into a suitable host organism.
  • the anti-LIGHT antibody (such as full-length anti-LIGHT antibody) can be a fully human antibody or a humanized antibody.
  • the humanized form of the non-human (such as mouse) antibody portion is a chimeric immunoglobulin, immunoglobulin chain or fragment thereof (such as Fv, Fab, Fab', F(ab') 2 , scFv or other antigen-binding subsequences of an antibody), which generally includes a minimum sequence derived from a non-human immunoglobulin.
  • Humanized antibodies include human immunoglobulins, immunoglobulin chains or fragments thereof (receptor antibodies), wherein the residues of the receptor CDR are replaced by non-human (donor antibody) CDR residues with the desired specificity, affinity and performance, such as mouse, rat or rabbit CDR.
  • human immunoglobulin Fv framework region residues are replaced by corresponding non-human residues.
  • Humanized antibodies can also include amino acid residues that are neither in the receptor antibody nor in the introduced CDR or framework region sequence.
  • a humanized antibody comprises at least one, usually two variable domains, wherein all or substantially all CDR regions correspond to the CDR regions of non-human immunoglobulins, and all or substantially all framework regions are human immunoglobulin consensus sequences.
  • a humanized antibody typically contains one or more amino acid residues introduced from a non-human source. Those non-human amino acid residues are often referred to as "imported” residues, usually from the "imported” variable domain.
  • humanization can be performed essentially according to the following method of Winter and his colleagues (Jones et al., Nature, 321: 522-525 (1986); Riechmann et al., Nature, 332: 323-327 (1988); Verhoeyen et al., Science, 239: 1534-1536 (1988)), by replacing the corresponding sequence of a human antibody with rodent CDRs or CDR sequences. Therefore, this "humanized” antibody portion (U.S. Patent No.
  • the humanized antibody portion is a typical human antibody portion in which some CDR residues and possibly some framework region residues are substituted by residues from analogous sites in rodent antibodies.
  • Fully human antibodies are an alternative to humanization.
  • transgenic animals e.g., mice
  • JH antibody heavy chain joining region
  • Transferring the human germline immunoglobulin gene array into such germline mutant mice can produce human antibodies under antigen stimulation, see, for example, akobovits et al., PNAS USA, 90: 2551 (1993); Jakobovits et al., Nature, 362: 255-258 (1993); Bruggemann et al., Year in Immunol., 7: 33 (1993); US Patent Nos. 5,545,806, 5,569,825, 5,591,669, 5,545,807; and WO 97/17852.
  • fully human antibodies can be prepared by introducing human immunoglobulin loci into transgenic animals (e.g., mice in which endogenous immunoglobulin genes have been partially or completely silenced).
  • Fully human antibodies can also be produced by in vitro activated B cells (see U.S. Patents 5,567,610 and 5,229,275) or by using various techniques known in the art, including phage display libraries. Hoogenboom and Winter, J. Mol. Biol., 227:381 (1991); Marks et al., J. Mol. Biol., 222:581 (1991). The techniques of Cole et al. and Boerner et al. can also be used to prepare fully human monoclonal antibodies. See Cole et al., Monoclonal Antibodies and Cancer Therapy, Alan R. Liss, p.77 (1985) and Boerner et al., J. Immunol., 147 (1): 86-95 (1991).
  • the amino acid sequences of anti-LIGHT antibody variants are also under consideration. For example, it may be necessary to improve the binding affinity and/or other biological activities of the antibody.
  • the amino acid sequence of the antibody variant can be prepared by introducing appropriate modifications in the nucleotide sequence encoding the antibody or by peptide synthesis. Such modifications include, for example, deletions and/or insertions and/or substitutions of residues in the antibody amino acid sequence.
  • the final construction can be completed by any combination of amino acid residue deletions, insertions and substitutions to give it the desired characteristics. For example, antigen binding.
  • anti-LIGHT antibody variants having one or more amino acid substitutions are provided.
  • the target sites of the substitution mutations include hypervariable regions (HVRs) and framework regions (FRs).
  • Amino acid substitutions can be introduced into the target antibody to screen for products of desired activity, for example, improved biological activity, maintaining/improving antigen binding ability, reduced immunogenicity, or improved ADCC or CDC.
  • Amino acids are divided into different categories based on the properties of their side chains:
  • Acidic amino acids Aspartic acid Asp, glutamic acid Glu;
  • Aromatic amino acids tryptophan Trp, tyrosine Tyr, phenylalanine Phe.
  • Non-conservative amino acid substitutions include substitutions of one class for another class.
  • An exemplary substitution variant is an affinity-matured antibody, which can be conveniently produced using, for example, affinity maturation techniques based on phage display.
  • one or more CDR residues are mutated, the variant antibody portion is displayed on the phage, and variants with specific biological activity (e.g., based on CD3 agonists and LIGHT co-stimulation of primary T cell activation and proliferation inhibition experiments or binding affinity biological activity) are screened.
  • Changes e.g., substitutions
  • Changes can be made in the "hotspots" of the HVR, i.e., residues encoded by codons that undergo high-frequency mutations during somatic maturation (see, e.g., Chowdhury, Methods Mol. Biol. 207: 179-196 (2008)), and/or at specific determinant residues (SDRs), and the binding affinity of the resulting variants V H and V L is detected.
  • SDRs specific determinant residues
  • diversity is introduced into the variable genes selected for affinity maturation by any of a variety of methods (e.g., error-prone PCR, chain shuffling, or oligonucleotide directed mutagenesis).
  • a secondary library is then created. The library is screened to identify antibody variants with the desired affinity.
  • Another method for introducing diversity includes HVR-mediated approaches, in which several HVR residues (e.g., 4-6 residues at a time) are randomized. HVR residues involved in antigen binding are specifically identified, for example, using alanine scanning mutagenesis or modeling. Typically, CDR-H3 and CDR-L3 regions are particularly key targets.
  • substitutions, insertions or deletions may occur within one or more HVRs, as long as such changes do not substantially reduce the ability of the antibody to bind antigen.
  • conservative changes that do not substantially reduce binding affinity can be produced in HVRs (e.g., conservative substitutions provided herein). These changes may occur outside the HVR "hotspots" or SDRs regions.
  • each HVR is either unchanged or contains no more than 1, 2 or 3 amino acid substitutions.
  • a useful method for identifying amino acid residues or regions in an antibody that can be targeted for mutation is called "alanine scanning mutagenesis," as described in Cunningham and Wells (1989) Science, 244: 1081-1085.
  • target residues e.g., charged residues such as arginine, aspartic acid, histidine, lysine, and glutamic acid
  • Amino acid (e.g., alanine or glutamic acid) substitutions are used to determine whether the antibody-antigen interaction is affected. Substitutions can be further introduced at the amino acid position to demonstrate that the position is functionally sensitive to the initial substitution.
  • the contact sites between the antibody and the antigen are identified by the crystal structure of the antigen-antibody complex. These contact site residues and adjacent residues can be targeted or eliminated as substitution candidates. Variants are screened to determine whether they have the desired properties.
  • Insertions of amino acid sequences include fusions at the amino and/or carboxyl termini ranging in length from 1 residue to polypeptides containing 100 or more residues, and also include insertions of 1 or more amino acid residues within a sequence.
  • Examples of terminal insertions include antibodies with a methionyl residue at the N-terminus.
  • Other insertion variants of antibody molecules include fusions of an enzyme (e.g., ADEPT) or a polypeptide that increases the serum half-life of the antibody molecule at the N-terminus or C-terminus.
  • one or more amino acid modifications are introduced into the Fc region of an antibody described herein (e.g., a full-length anti-LIGHT antibody or an anti-LIGHT antibody fusion protein), thereby generating an Fc region variant.
  • the Fc region variant has enhanced ADCC potency, typically associated with receptors (FcRs) that bind to Fc.
  • the Fc region variant has reduced ADCC potency.
  • ADCC Antibody-dependent cell-mediated cytotoxicity
  • NK cells activated by antibodies.
  • NK cells express the Fc receptor CD16. This receptor recognizes and binds to the Fc portion of antibody molecules bound to the surface of target cells.
  • the most common Fc receptors on the surface of NK cells are CD16 or Fc ⁇ RIII.
  • the binding of Fc receptors to the Fc region of antibodies leads to the activation of NK cells, the release of cell lytic granules, and subsequent apoptosis of target cells.
  • the killing effect of ADCC on tumor cells can be determined by specific experiments of NK-92 cells transfected with high-affinity FcR. The results are compared with wild-type NK-92 that do not express FcR.
  • the present application also provides anti-LIGHT antibody variants (e.g., full-length anti-LIGHT antibody variants) comprising an Fc region with some but not all effector functions, so that it has an extended half-life in vivo, but a specific effector function (e.g., CDC or ADCC) is non-essential or harmful, and such anti-LIGHT antibodies become ideal candidates for the present application.
  • anti-LIGHT antibody variants e.g., full-length anti-LIGHT antibody variants
  • an Fc region with some but not all effector functions e.g., CDC or ADCC
  • CDC or ADCC e.g., CDC or ADCC
  • the reduction/elimination of CDC and/or ADCC activity is confirmed by cytotoxicity detection in vitro and/or in vivo.
  • an Fc receptor (FcR) binding assay is used to confirm that the antibody lacks Fc ⁇ R binding ability (and therefore may lack ADCC activity) but still retains FcRn binding ability.
  • NK cells express only Fc ⁇ RIII, while monocytes express Fc ⁇ RI, Fc ⁇ RII, and Fc ⁇ RIII.
  • the expression of FcR on hematopoietic cells is summarized in Table 3 on page 464 of Ravetch and Kinet Annu.Rev.Immunol.9:457-492 (1991).
  • Non-limiting examples of in vitro assessment of ADCC activity of a target molecule are described in US Pat. No. 5,500,362 (see, e.g., Hellstrom, I. et al. Proc. Nat'l Acad. Sci. USA 83:7059-7063 (1986) and Hellstrom, I et al., Proc.
  • non-radioactive detection methods can be used (see, e.g., ACTI TM flow cytometry non-radioactive cytotoxicity assay (Cell Technology, Inc. Mountain View, Calif.) and CYTOTOX 96 TM Non-Radioactive Cytotoxicity Assay (Promega, Madison, Wis.). Effector cells used in such assays include peripheral blood mononuclear cells (PBMC) and natural killer cells (NK).
  • PBMC peripheral blood mononuclear cells
  • NK natural killer cells
  • ADCC activity of the target molecule is tested in vivo, for example, in an animal model as described in Clynes et al. Proc. Nat'l Acad. Sci. USA 95:652-656 (1998).
  • a C1q binding assay can also be performed to confirm that the antibody cannot bind to C1q and thus lacks CDC activity. See, for example, C1q and C3c binding ELISA in WO 2006/029879 and WO 2005/100402.
  • a CDC assay can be performed (see, e.g., Gazzano-Santoro et al., J. Immunol.
  • FcRn binding and in vivo clearance/half-life can be determined using methods known in the art (see, e.g., Petkova, SB et al., Int'l. Immunol. 18(12): 1759-1769 (2006)).
  • Antibodies with reduced effector function include substitutions of one or more residues at residues 238, 265, 269, 270, 297, 327, and 329 in the Fc region (U.S. Pat. No. 6,737,056). These Fc variants include Fc variants with substitutions of two or more residues at positions 265, 269, 270, 297, and 327, including an Fc variant known as "DANA" in which residues 265 and 297 are substituted with alanine (U.S. Pat. No. 7,332,581).
  • an anti-LIGHT antibody (e.g., full-length anti-LIGHT antibody) variant comprising an Fc region variant having one or more amino acid substitutions capable of enhancing ADCC effects.
  • the Fc region variant comprises one or more amino substitutions capable of enhancing ADCC effects, and the positions of these substitutions are at positions 298, 333, and/or 334 (EU residue numbering) in the Fc region.
  • the anti-LIGHT antibody (e.g., full-length anti-LIGHT antibody) variant includes amino acid substitutions at positions S298A, E333A, and K334A in the Fc region.
  • alterations in the Fc region result in alterations (i.e., enhancement or reduction) in C1q binding and/or complement-dependent cytotoxicity (CDC), as described in U.S. Pat. No. 6,194,551, WO 99/51642, and Idusogie et al., J. Immunol. 164: 4178-4184 (2000).
  • CDC complement-dependent cytotoxicity
  • an anti-LIGHT antibody e.g., a full-length anti-LIGHT antibody
  • an Fc region variant having one or more amino acid substitutions, capable of extending half-life or enhancing binding to an Fc receptor (FcRn).
  • FcRn Fc receptor
  • Antibodies with extended half-life and improved FcRn binding are described in US 2005/0014934A1 (Hinton et al.). These antibody Fc regions comprise one or more amino acid substitutions that enhance binding of the Fc region to FcRn.
  • Fc variants comprise one or more substitutions in the Fc region at residues at positions 238, 256, 265, 272, 286, 303, 305, 307, 311, 312, 317, 340, 356, 360, 362, 376, 378, 380, 382, 413, 424, or 434, such as substitutions at residue position 434 in the Fc region (U.S. Pat. No. 7,371,826).
  • an anti-LIGHT antibody eg, a full-length anti-LIGHT antibody
  • an anti-LIGHT antibody comprising any one of the Fc variants described herein or a combination thereof.
  • the anti-LIGHT antibodies (e.g., full-length anti-LIGHT antibodies) provided herein are altered to increase or decrease the degree of glycosylation of the anti-NGF antibodies. Adding or deleting glycosylation sites on the anti-LIGHT antibodies can be conveniently achieved by changing the amino acid sequence of the anti-NGF antibody or its polypeptide portion to increase or remove one or more glycosylation sites.
  • the anti-LIGHT antibody comprises an Fc region
  • the sugar connected thereto can be changed.
  • Natural antibodies produced by mammalian cells generally contain branched biantennary oligosaccharides, which are generally connected to the Fc region CH2 domain Asn297 via an N-link, see, for example, Wright et al., TIBTECH 15: 26-32 (1997).
  • the oligosaccharides may contain a variety of carbohydrates, such as mannose, N-acetylglucosamine (GlcNAc), galactose and sialic acid, and trehalose connected to the GlcNAc of the "stem" of the biantennary oligosaccharide structure.
  • the anti-LIGHT antibodies of the present application may be oligosaccharide-modified to produce anti-LIGHT antibody variants with certain improved properties.
  • N-glycans attached to the CH2 domain of the Fc region are heterogeneous.
  • Antibodies or Fc fusion proteins produced in CHO cells are fucosylated by fucosyltransferase activity, see Shoji-Hosaka et al., J. Biochem. 2006, 140: 777-83.
  • a small fraction of naturally occurring non-fucosylated IgGs can be detected in human serum.
  • N-glycosylation of the Fc region is important for its binding to Fc ⁇ R; while non-fucosylated N-glycans enhance the binding ability of Fc to Fc ⁇ RIIIa.
  • Enhanced binding ability to FcRIIIa enhances the ADCC effect, which is advantageous in certain antibody therapeutic applications requiring cytotoxicity.
  • the enhanced effector function may be detrimental.
  • the Fc fragment or CH2 domain is non-glycosylated.
  • the N-glycosylation site in the CH2 domain is mutated to prevent glycosylation.
  • an anti-LIGHT antibody (e.g., a full-length anti-LIGHT antibody) variant is provided, which comprises an Fc region, wherein the carbohydrate structure connected to the Fc region has reduced fucose or lacks fucose, which may enhance ADCC function.
  • anti-LIGHT antibodies are provided herein, which have reduced fucose relative to the same anti-LIGHT antibodies produced by wild-type CHO cells. That is, they are characterized in that they have less fucose than antibodies produced by natural CHO cells (e.g., CHO cells producing natural glycosylation forms, CHO cells containing natural FUT8 genes).
  • the N-linked glycans of the anti-LIGHT antibody have less than 50%, 40%, 30%, 20%, 10% or 5% fucose.
  • the fucose content of the anti-LIGHT antibody may be 1%-80%, 1%-65%, 5%-65% or 20%-40%.
  • the N-linked glycans of the anti-LIGHT antibody do not contain fucose, that is, the anti-LIGHT antibody is completely free of fucose, or has no fucose or is defucosylated.
  • the content of fucose is determined by calculating the average content of fucose in the sugar chain connected to Asn297 relative to the total amount of all sugar structures (such as complex, hybrid or mannose structures) connected to Asn297 measured by MALDI-TOF mass spectrometry, as described in WO 2008/077546.
  • Asn297 refers to the asparagine residue located at position 297 of the Fc region (EU Fc region residue numbering system). However, due to minor sequence variations of antibodies, Asn297 may also be located ⁇ 3 amino acids upstream or downstream of position 297, i.e., between positions 294 and 300. These fucosylated variants may have enhanced ADCC function. See, e.g., US Patent Publication Nos.
  • Cell lines capable of producing defucosylated antibodies include Lec13 CHO cells lacking protein fucosylation function (Ripka et al. Arch. Biochem. Biophys. 249: 533-545 (1986); US Pat Appl No US 2003/0157108 A1, Presta, L; and WO 2004/056312 A1, Adams et al., especially Example 11), and gene knockout cell lines, such as CHO cells in which the ⁇ -1,6-fucosyltransferase gene, FUT8 gene is knocked out (see Yamane-Ohnuki et al. Biotech. Bioeng. 87: 614 (2004); Kanda, Y. et al., Biotechnol. Bioeng., 94 (4): 680-688 (2006); and WO 2003/085107).
  • Anti-LIGHT antibody (e.g., full-length anti-LIGHT antibody) variants further provide bisected oligosaccharides, for example, wherein the biantennary oligosaccharide attached to the Fc region of the anti-LIGHT antibody is bisected by GlcNAc.
  • Such anti-LIGHT antibody (e.g., full-length anti-LIGHT antibody) variants may have reduced fucosylation and/or enhanced ADCC function. Examples of such antibody variants are described in WO 2003/011878 (Jean-Mairet et al.); U.S. Pat. No.
  • Anti-LIGHT antibody e.g., full-length anti-LIGHT antibody
  • Anti-LIGHT antibody variants are also provided, which have at least one galactose residue in the oligosaccharide attached to the Fc region.
  • Such anti-LIGHT antibody variants may have enhanced CDC function.
  • Such variants are described in, for example, WO 1997/30087 (Patel et al.); WO 1998/58964 (Raju, S.); and WO 1999/22764 (Raju, S.).
  • the anti-LIGHT antibody (e.g., full-length anti-LIGHT antibody) variant comprises an Fc region that can bind to Fc ⁇ RIII.
  • the anti-LIGHT antibody (e.g., full-length anti-LIGHT antibody) variant comprising an Fc region has ADCC activity in the presence of human effector cells (e.g., T cells), or has enhanced ADCC activity in the presence of human effector cells compared to other identical anti-LIGHT antibodies (e.g., full-length anti-LIGHT antibodies) having human wild-type IgG1 Fc regions.
  • cysteine engineered anti-LIGHT antibodies e.g., full-length anti-LIGHT antibodies
  • the substituted residues appear at accessible sites of anti-LIGHT antibodies.
  • active sulfhydryl groups are located at accessible sites of anti-LIGHT antibodies, which can be used to couple the anti-LIGHT antibodies to other moieties, such as drug moieties or linker-drug moieties, to prepare anti-LIGHT immunoconjugates as further described herein.
  • Cysteine engineered anti-LIGHT antibodies e.g., full-length anti-LIGHT antibodies
  • the anti-LIGHT antibodies e.g., full-length anti-LIGHT antibodies
  • Suitable moieties for derivatizing anti-LIGHT antibodies include, but are not limited to, water-soluble polymers.
  • Non-limiting examples of water-soluble polymers include, but are not limited to, polyethylene glycol (PEG), ethylene glycol/propylene glycol copolymers, carboxymethyl cellulose, dextran, polyvinyl alcohol, polyvinyl pyrrolidone, poly-1,3-dioxolane, poly- 1,3,6-trioxane, ethylene/maleic anhydride copolymers, polyamino acids (homopolymers or random copolymers), dextran or poly(n-vinyl pyrrolidone) polyethylene glycol, propylene glycol homopolymers, propylene oxide/ethylene oxide copolymers, polyoxyethylated polyols (e.g., glycerol), polyvinyl alcohol, and mixtures thereof.
  • PEG polyethylene glycol
  • ethylene glycol/propylene glycol copolymers carboxymethyl cellulose
  • dextran polyvinyl alcohol
  • polyvinyl pyrrolidone poly
  • Polyethylene glycol propionaldehyde has advantages in manufacturing due to its stability in water.
  • the polymer can have any molecular weight and can be branched or unbranched.
  • the number of polymers attached to the anti-LIGHT antibody can vary, and if more than one polymer is attached, they can be the same or different molecules. Generally, the number and/or type of polymers used for derivatization can be determined based on the following considerations, including but not limited to, the need to improve the properties or functions of the anti-LIGHT antibody, whether the anti-LIGHT antibody derivative is used for treatment under specific conditions, etc.
  • compositions e.g., pharmaceutical compositions, also referred to herein as preparations
  • any anti-LIGHT antibody e.g., full-length anti-LIGHT antibody
  • nucleic acids encoding antibodies e.g., full-length anti-LIGHT antibody
  • vectors comprising nucleic acids encoding antibodies
  • host cells comprising nucleic acids or vectors described herein.
  • a pharmaceutical composition comprising any anti-LIGHT antibody described herein and a pharmaceutically acceptable carrier.
  • Suitable anti-LIGHT antibody preparations can be obtained by mixing an anti-LIGHT antibody having the desired purity with an optional pharmaceutically acceptable carrier, excipient or stabilizer (Remington's Pharmaceutical Sciences 16th edition, Osol, A. Ed. (1980)) and prepared in the form of a lyophilized preparation or a liquid preparation.
  • Acceptable carriers, excipients or stabilizers are non-toxic to recipients at the dosages and concentrations used, and include buffers such as phosphates, citric acid and other organic acids; antioxidants, including ascorbic acid and methionine; preservatives (e.g., octadecyldimethylbenzyl ammonium chloride; hexamethylammonium chloride; benzalkonium chloride; benzethonium chloride; phenol; butyl alcohol or benzyl alcohol; alkyl parabens, such as methyl paraben or propyl paraben; catechol; resorcinol; cyclohexanol; 3-pentanol and m-cresol); low molecular weight (less than 1 0 residues) polypeptide; protein, such as serum albumin, gelatin or immunoglobulin; hydrophilic polymer, such as polyvinylpyrrolidone; amino acids, such as glycine, glutamine, as
  • Lyophilized formulations suitable for subcutaneous administration are described in WO97/04801. Such lyophilized formulations can be reconstituted into high protein concentration formulations by suitable diluents, and the reconstituted formulations can be administered to the individual to be treated herein by subcutaneous administration. Cationic liposomes or liposomes can be used to deliver the anti-LIGHT antibodies in the present application to cells.
  • the formulations described herein may also include one or more other active substances necessary for treating specific diseases, preferably substances with complementary activities and no adverse reactions to each other.
  • active substances e.g., steroids, non-steroidal anti-inflammatory drugs (NSAIDS) (e.g., salicylates, propionic acid derivatives, acetic acid derivatives, enolic acid derivatives, o-aminophenyl acid derivatives, selective COX-2 inhibitors and sulfonanilides), glucocorticoids (e.g., cortisol, cortisone, prednisone, prednisolone, dexamethasone, betamethasone, triamcinolone, etc.), cytostatics (e.g., alkylating agents, antimetabolites, methotrexate, thiopurine, mercaptopurine or cytotoxic antibiotics).
  • NSAIDS non-steroidal anti-inflammatory drugs
  • glucocorticoids e.g., cortisol,
  • the invention also includes the following: anti-LIGHT antibodies (anti-LIGHT antibodies), TNF inhibitors, IL-12 inhibitors, IL-23 inhibitors, ⁇ 4 ⁇ 7 integrin inhibitors. These molecules are present in combination in an amount effective for the intended purpose. The effective amount of other substances depends on the content of the anti-LIGHT antibody in the preparation, the type of disease or disorder or treatment, and other factors as described above. These drugs are generally used in the same dosage and administration route as described herein, or in 1% to 99% of the currently used dosage.
  • the anti-LIGHT antibody (e.g., full-length anti-LIGHT antibody) can also be embedded in microcapsules prepared, for example, by coacervation techniques and interfacial polymerization, such as hydroxymethylcellulose or gelatin-microcapsules and poly(methyl methacrylate) microcapsules in colloidal drug delivery systems (e.g., liposomes, albumin microspheres, microemulsions, nanoparticles, and nanocapsules) or in macroemulsions, respectively. Sustained-release preparations can be prepared.
  • sustained-release formulations of anti-LIGHT antibodies can be prepared.
  • suitable examples of sustained-release formulations include solid hydrophobic polymer semipermeable matrices containing antibodies (or fragments thereof), which are in the form of shaped articles, such as films or microcapsules.
  • sustained-release matrices include polyesters, hydrogels (e.g., poly(2-hydroxyethyl methacrylate) or poly(vinyl alcohol)), polylactic acid (U.S. Pat. No.
  • copolymers of L-glutamic acid and ethyl L-glutamate non-degradable ethylene-vinyl acetate, degradable lactic acid-glycolic acid copolymers such as LUPRON DEPOTTM (injectable microspheres composed of lactic acid-glycolic acid copolymer and leuprolide acetate), and poly-D(-)-3-hydroxybutyric acid.
  • LUPRON DEPOTTM injectable microspheres composed of lactic acid-glycolic acid copolymer and leuprolide acetate
  • poly-D(-)-3-hydroxybutyric acid polymers such as ethylene-vinyl acetate and lactic acid-glycolic acid can allow the release of molecules for more than 100 days, certain hydrogels can release proteins for shorter periods of time.
  • encapsulated antibodies When encapsulated antibodies remain in the body for a long time, they can denature or aggregate due to exposure to a humid environment at 37°C, which may lead to loss of biological activity or changes in immunogenicity. Rational strategies can be designed to stabilize anti-LIGHT antibodies based on the corresponding mechanisms. For example, if the aggregation mechanism is found to be the formation of intermolecular S-S bonds through thiodisulfide exchange, stabilization can be achieved by modifying thiol residues, lyophilizing in acidic solutions, controlling water content, using appropriate additives, and developing specific polymer matrix compositions.
  • the anti-LIGHT antibody (eg, full length anti-LIGHT antibody) is formulated in a buffer containing citrate, sodium chloride, acetate, succinate, glycine, polysorbate 80 (Tween 80), or any combination thereof.
  • Preparations for in vivo administration must be sterile. This can be easily achieved, for example, by filtration through sterile filtration membranes.
  • Anti-LIGHT antibodies e.g., full-length anti-LIGHT antibodies
  • compositions described herein can be administered to an individual (e.g., a mammal, such as a human) to treat diseases and/or conditions (e.g., autoimmune diseases and/or inflammatory diseases) caused by dysregulation of the LIGHT signaling pathway, including but not limited to inflammatory bowel disease (IBD), Crohn's disease, ulcerative colitis, ankylosing spondylitis, atopic dermatitis, rheumatoid arthritis, bronchiolitis, transplant rejection, allograft rejection, graft-versus-host disease (GV HD), asthma, eosinophilic esophagitis, acute respiratory distress syndrome (ARDS), chronic heart failure, chronic obstructive pulmonary disease (COPD), septic shock, fibrotic diseases, skin fibrosis, idiopathic pulmonary fibrosis, renal fibrosis, chronic kidney disease, systemic sclerosis, multiple sclerosis
  • a method for treating a disease and/or condition comprising administering to an individual an effective amount of a composition (e.g., a pharmaceutical composition) comprising an anti-LIGHT antibody (e.g., a full-length anti-LIGHT antibody), such as any anti-LIGHT antibody (e.g., a full-length anti-LIGHT antibody) described herein, wherein in some embodiments, the individual is human.
  • a composition e.g., a pharmaceutical composition
  • an anti-LIGHT antibody e.g., a full-length anti-LIGHT antibody
  • any anti-LIGHT antibody e.g., a full-length anti-LIGHT antibody
  • a method for treating an individual suffering from a disease associated with a LIGHT signaling pathway comprising administering to the individual an effective amount of a pharmaceutical composition comprising a LIGHT antibody (e.g., a full-length anti-LIGHT antibody) that specifically binds to an epitope on human LIGHT, wherein the epitope comprises an amino acid residue at position 20 of human LIGHT.
  • a LIGHT antibody e.g., a full-length anti-LIGHT antibody
  • the anti-LIGHT antibody is a full-length antibody.
  • the full-length anti-LIGHT antibody is an IgG1 or IgG4 antibody.
  • the disease or condition is selected from, for example, inflammatory bowel disease (IBD), Crohn's disease, ulcerative colitis, ankylosing spondylitis, atopic dermatitis, rheumatoid arthritis, bronchiolitis, transplant rejection, allograft rejection, graft-versus-host disease (GVHD), asthma, eosinophilic esophagitis, acute respiratory distress syndrome (ARDS), chronic heart failure, chronic obstructive pulmonary disease (COPD), septic shock, fibrotic diseases, skin fibrosis, idiopathic pulmonary fibrosis, renal fibrosis, chronic kidney disease, systemic sclerosis, multiple sclerosis, Sjögren's syndrome, lupus, airway inflammation, psoriasis, hepatitis, celiac disease, primary biliary cirrhosis, autoimmune hemolytic anemia, autoimmune neonatal thrombocytopenia, idiopathic thro
  • a method for treating an individual having a disease associated with a LIGHT signaling pathway comprising administering to the individual an effective amount of a pharmaceutical composition comprising an anti-LIGHT antibody (e.g., a full-length anti-LIGHT antibody), wherein the antibody comprises: a heavy chain variable domain ( VH ), the VH comprising: a heavy chain complementary determining region (HC-CDR) 1 comprising GYFIN (SEQ ID NO: 1); HC-CDR2 comprising RIYPYNVX1TFYNQNFKG (SEQ ID NO: 45), wherein X1 is D or N; and HC-CDR3 comprising GTHYYGSSGAMDY (SEQ ID NO: 16); and a light chain variable domain ( VL ), the VL comprising: a light chain complementary determining region (LC-CDR) 1 comprising KASQNVGTAVA (SEQ ID NO: 23);
  • the anti-LIGHT antibody is a full-length antibody. In some embodiments, the full-length anti-LIGHT antibody is an IgG1 or IgG4 antibody.
  • the disease or condition is selected from, for example, inflammatory bowel disease (IBD), Crohn's disease, ulcerative colitis, ankylosing spondylitis, atopic dermatitis, rheumatoid arthritis, bronchiolitis, transplant rejection, allograft rejection, graft-versus-host disease (GVHD), asthma, eosinophilic esophagitis, acute respiratory distress syndrome (ARDS), chronic heart failure, chronic obstructive pulmonary disease (COPD), septic shock, fibrotic diseases, skin fibrosis, idiopathic pulmonary fibrosis, renal fibrosis, chronic kidney disease, systemic sclerosis, multiple sclerosis, Sjögren's syndrome, lupus, airway inflammation, psoriasis, hepati
  • IBD inflammatory
  • a method for treating an individual suffering from a disease associated with a LIGHT signaling pathway comprising administering to the individual an effective amount of a composition comprising an anti-LIGHT antibody, wherein the antibody comprises a VH comprising: a HC-CDR1 comprising the amino acid sequence shown in SEQ ID NO: 1, a HC-CDR2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 8-9, and a HC-CDR3 comprising the amino acid sequence shown in SEQ ID NO: 16, or a variant of the VH comprising up to about 5 amino acid substitutions in its HC-CDRs; and a VL comprising: a LC-CDR1 comprising the amino acid sequence shown in SEQ ID NO: 23, a LC-CDR2 comprising the amino acid sequence shown in SEQ ID NO: 30, and a LC-CDR3 comprising the amino acid sequence shown in SEQ ID NO
  • a method for treating an individual suffering from a disease associated with the LIGHT signaling pathway comprising administering to the individual an effective amount of a composition comprising an anti-LIGHT antibody, wherein the antibody comprises: a VH comprising an amino acid sequence as shown in any one of SEQ ID NOs:46-53 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence as shown in any one of SEQ ID NOs:46-53; and a VL comprising an amino acid sequence as shown in any one of SEQ ID NOs:62-65 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence as shown in any one of SEQ ID NOs:62-65.
  • the anti-LIGHT antibody described herein is a full-length anti-LIGHT antibody comprising an IgG1 or IgG4 constant region.
  • the IgG1 is human IgG1.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:74.
  • the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:75.
  • the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO:76.
  • the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO:77.
  • a method for treating an individual suffering from a disease associated with a LIGHT signaling pathway comprising administering to the individual an effective amount of a composition comprising an anti-LIGHT antibody, wherein the antibody comprises: a VH comprising: a HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, a HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 8, and a HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 16, or a variant of the VH comprising substitutions of up to about 5 amino acids in its HC-CDRs; and a VL comprising: a LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 23, a LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 30, and a LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 37, or a variant of the VH comprising: a HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1,
  • the anti-LIGHT antibodies described herein comprise: a VH comprising the amino acid sequence of SEQ ID NO:46 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:46; and a VL comprising the amino acid sequence of SEQ ID NO:62 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:62.
  • the anti-LIGHT antibodies described herein are full-length anti-LIGHT antibodies comprising an IgG1 or IgG4 constant region.
  • the IgG1 is human IgG1.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 75. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 77.
  • the anti-LIGHT antibodies described herein comprise: a VH comprising the amino acid sequence of SEQ ID NO: 47 or a variant thereof having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 47; and a VL comprising the amino acid sequence of SEQ ID NO: 63 or a variant thereof having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 63.
  • the anti-LIGHT antibodies described herein are full-length anti-LIGHT antibodies comprising an IgG1 or IgG4 constant region.
  • the IgG1 is a human IgG1.
  • the IgG4 is a human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 74. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 75. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 77.
  • the anti-LIGHT antibody described herein comprises: a VH comprising the amino acid sequence of SEQ ID NO: 48 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 48; and a VL comprising the amino acid sequence of SEQ ID NO: 63 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 63.
  • the anti-LIGHT antibody described herein is a full-length anti-LIGHT antibody comprising an IgG1 or IgG4 constant region.
  • the IgG1 is a human IgG1.
  • the IgG4 is a human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 74. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 75. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 77.
  • the anti-LIGHT antibody described herein comprises: a VH comprising the amino acid sequence of SEQ ID NO: 49 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 49; and a VL comprising the amino acid sequence of SEQ ID NO: 63 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 63.
  • the anti-LIGHT antibody described herein is a full-length anti-LIGHT antibody comprising an IgG1 or IgG4 constant region.
  • the IgG1 is a human IgG1.
  • the IgG4 is a human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 74. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 75. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 77.
  • the anti-LIGHT antibodies described herein comprise: a VH comprising the amino acid sequence of SEQ ID NO: 50 or a variant thereof having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 50; and a VL comprising the amino acid sequence of SEQ ID NO: 63 or a variant thereof having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 63.
  • the anti-LIGHT antibodies described herein are full-length anti-LIGHT antibodies comprising an IgG1 or IgG4 constant region.
  • the IgG1 is a human IgG1.
  • the IgG4 is a human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 74. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 75. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 77.
  • the anti-LIGHT antibodies described herein comprise: a VH comprising the amino acid sequence of SEQ ID NO: 47 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 47; and a VL comprising the amino acid sequence of SEQ ID NO: 64 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 64.
  • the anti-LIGHT antibodies described herein are full-length anti-LIGHT antibodies comprising an IgG1 or IgG4 constant region.
  • the IgG1 is a human IgG1.
  • the IgG4 is a human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 74. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 75. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 77.
  • the anti-LIGHT antibodies described herein comprise: a VH comprising the amino acid sequence of SEQ ID NO: 48 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 48; and a VL comprising the amino acid sequence of SEQ ID NO: 64 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 64.
  • the anti-LIGHT antibodies described herein are full-length anti-LIGHT antibodies comprising an IgG1 or IgG4 constant region.
  • the IgG1 is a human IgG1.
  • the IgG4 is a human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 74. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 75. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 77.
  • the anti-LIGHT antibodies described herein comprise: a VH comprising the amino acid sequence of SEQ ID NO: 49 or a variant thereof having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 49; and a VL comprising the amino acid sequence of SEQ ID NO: 64 or a variant thereof having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 64.
  • the anti-LIGHT antibodies described herein are full-length anti-LIGHT antibodies comprising an IgG1 or IgG4 constant region.
  • the IgG1 is a human IgG1.
  • the IgG4 is a human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 74. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 75. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 77.
  • the anti-LIGHT antibodies described herein comprise: a VH comprising the amino acid sequence of SEQ ID NO: 50 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 50; and a VL comprising the amino acid sequence of SEQ ID NO: 64 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 64.
  • the anti-LIGHT antibodies described herein are full-length anti-LIGHT antibodies comprising an IgG1 or IgG4 constant region.
  • the IgG1 is a human IgG1.
  • the IgG4 is a human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 74. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 75. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 77.
  • the anti-LIGHT antibodies described herein comprise: a VH comprising the amino acid sequence of SEQ ID NO: 47 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 47; and a VL comprising : Comprising the amino acid sequence of SEQ ID NO:65 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:65.
  • the anti-LIGHT antibody described herein is a full-length anti-LIGHT antibody comprising an IgG1 or IgG4 constant region.
  • the IgG1 is a human IgG1.
  • the IgG4 is a human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:75. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77.
  • the anti-LIGHT antibodies described herein comprise: a VH comprising the amino acid sequence of SEQ ID NO: 48 or a variant thereof having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 48; and a VL comprising the amino acid sequence of SEQ ID NO: 65 or a variant thereof having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 65.
  • the anti-LIGHT antibodies described herein are full-length anti-LIGHT antibodies comprising an IgG1 or IgG4 constant region.
  • the IgG1 is a human IgG1.
  • the IgG4 is a human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 74. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 75. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 77.
  • the anti-LIGHT antibodies described herein comprise: a VH comprising the amino acid sequence of SEQ ID NO: 49 or a variant thereof having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 49; and a VL comprising the amino acid sequence of SEQ ID NO: 65 or a variant thereof having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 65.
  • the anti-LIGHT antibodies described herein are full-length anti-LIGHT antibodies comprising an IgG1 or IgG4 constant region.
  • the IgG1 is a human IgG1.
  • the IgG4 is a human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 74. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 75. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 77.
  • the anti-LIGHT antibodies described herein comprise: a VH comprising the amino acid sequence of SEQ ID NO: 50 or a variant thereof having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 50; and a VL comprising the amino acid sequence of SEQ ID NO: 65 or a variant thereof having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 65.
  • the anti-LIGHT antibodies described herein are full-length anti-LIGHT antibodies comprising an IgG1 or IgG4 constant region.
  • the IgG1 is a human IgG1.
  • the IgG4 is a human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 74. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 75. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 77.
  • a method for treating an individual suffering from a disease associated with a LIGHT signaling pathway comprising administering to the individual an effective amount of a composition comprising an anti-LIGHT antibody, wherein the antibody comprises: a VH , wherein the VH comprises: an HC-CDR1 comprising an amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising an amino acid sequence of SEQ ID NO: 9, and an HC-CDR3 comprising an amino acid sequence of SEQ ID NO: 16, or A variant of the V H comprising substitutions of up to about 5 amino acids in its HC-CDRs; and a V L comprising: a LC-CDR1 comprising the amino acid sequence of SEQ ID NO:23, a LC-CDR2 comprising the amino acid sequence of SEQ ID NO:30, and a LC-CDR3 comprising the amino acid sequence of SEQ ID NO:37, or a
  • the anti-LIGHT antibodies described herein comprise: a VH comprising an amino acid sequence of SEQ ID NO: 51 or a variant thereof having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 51; and a VL comprising an amino acid sequence of SEQ ID NO: 63 or a variant thereof having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 63.
  • the anti-LIGHT antibodies described herein are full-length anti-LIGHT antibodies comprising an IgG1 or IgG4 constant region.
  • the IgG1 is a human IgG1.
  • the IgG4 is a human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 74. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 75. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 77.
  • the anti-LIGHT antibodies described herein comprise: a VH comprising an amino acid sequence of SEQ ID NO: 52 or a variant thereof having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 52; and a VL comprising an amino acid sequence of SEQ ID NO: 65 or a variant thereof having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 65.
  • the anti-LIGHT antibodies described herein are full-length anti-LIGHT antibodies comprising an IgG1 or IgG4 constant region.
  • the IgG1 is a human IgG1.
  • the IgG4 is a human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 74. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 75. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 77.
  • the anti-LIGHT antibodies described herein comprise: a VH comprising an amino acid sequence of SEQ ID NO: 53 or a variant thereof having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 53; and a VL comprising an amino acid sequence of SEQ ID NO: 65 or a variant thereof having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 65.
  • the anti-LIGHT antibodies described herein are full-length anti-LIGHT antibodies comprising an IgG1 or IgG4 constant region.
  • the IgG1 is a human IgG1.
  • the IgG4 is a human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 74. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 75. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 77.
  • the anti-LIGHT antibodies described herein comprise: a VH comprising the amino acid sequence of SEQ ID NO:51 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:51; and a VL comprising the amino acid sequence of SEQ ID NO:65 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:65.
  • the anti-LIGHT antibodies described herein are full-length anti-LIGHT antibodies comprising an IgG1 or IgG4 constant region.
  • the IgG1 is human IgG1.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:74. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 75. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 77.
  • a method for treating an individual suffering from a disease associated with a LIGHT signaling pathway comprising administering to the individual an effective amount of a pharmaceutical composition comprising an anti-LIGHT antibody (e.g., a full-length anti-LIGHT antibody), wherein the antibody comprises: a heavy chain variable domain ( VH ), the VH comprising: a HC-CDR1 comprising the amino acid sequence of SEQ ID NO:2, a HC-CDR2 comprising the amino acid sequence of SEQ ID NO:10, and a HC-CDR3 comprising the amino acid sequence of SEQ ID NO:17, or a variant of the VH comprising up to about 5 amino acid substitutions in its HC-CDRs; and a light chain variable domain ( VL ), the VL comprising: a LC-CDR1 comprising the amino acid sequence of SEQ ID NO:24, a LC-CDR2 compris
  • the anti-LIGHT antibody is a full-length antibody. In some embodiments, the full-length anti-LIGHT antibody is an IgG1 or IgG4 antibody.
  • the disease or condition is selected from, for example, inflammatory bowel disease (IBD), Crohn's disease, ulcerative colitis, ankylosing spondylitis, atopic dermatitis, rheumatoid arthritis, bronchiolitis, transplant rejection, allograft rejection, graft-versus-host disease (GVHD), asthma, eosinophilic esophagitis, acute respiratory distress syndrome (ARDS), chronic heart failure, chronic obstructive pulmonary disease (COPD), septic shock, fibrotic disease, skin fibrosis, idiopathic pulmonary fibrosis, renal fibrosis, chronic kidney disease, systemic sclerosis, multiple sclerosis, Sjögren's syndrome, lupus, airway inflammation, psoriasis, hepati
  • IBD inflammatory
  • a method for treating an individual suffering from a disease associated with the LIGHT signaling pathway comprising administering to the individual an effective amount of a composition comprising an anti-LIGHT antibody, wherein the antibody comprises: a VH comprising the amino acid sequence shown in SEQ ID NO:54 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO:54; and a VL comprising the amino acid sequence shown in SEQ ID NO:66 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO:66.
  • a disease associated with the LIGHT signaling pathway e.g., an autoimmune disease and/or an inflammatory disease
  • the anti-LIGHT antibody described herein is a full-length anti-LIGHT antibody comprising an IgG1 or IgG4 constant region.
  • the IgG1 is human IgG1.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:74.
  • the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:75.
  • the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO:76.
  • the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO:77.
  • a method for treating an individual suffering from a disease associated with a LIGHT signaling pathway comprising administering to the individual an effective amount of a pharmaceutical composition comprising an anti-LIGHT antibody (e.g., a full-length anti-LIGHT antibody), wherein the antibody comprises: a heavy chain variable domain ( VH ), the VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 3 NO:10, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO:17, or a variant of said V H , wherein the HC-CDRs thereof comprise substitutions of up to about 5 amino acids; and a light chain variable domain (V L ), wherein the V L comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:25, LC-CDR2 comprising the
  • the anti-LIGHT antibody is a full-length antibody. In some embodiments, the full-length anti-LIGHT antibody is an IgG1 or IgG4 antibody.
  • the disease or condition is selected from, for example, inflammatory bowel disease (IBD), Crohn's disease, ulcerative colitis, ankylosing spondylitis, atopic dermatitis, rheumatoid arthritis, bronchiolitis, transplant rejection, allograft rejection, graft-versus-host disease (GVHD), asthma, eosinophilic esophagitis, acute respiratory distress syndrome (ARDS), chronic heart failure, chronic obstructive pulmonary disease (COPD), septic shock, fibrotic diseases, skin fibrosis, idiopathic pulmonary fibrosis, renal fibrosis, chronic kidney disease, systemic sclerosis, multiple sclerosis, Sjögren's syndrome, lupus, airway inflammation, psoriasis, hepati
  • IBD inflammatory
  • a method for treating an individual suffering from a disease associated with the LIGHT signaling pathway comprising administering to the individual an effective amount of a composition comprising an anti-LIGHT antibody, wherein the antibody comprises: a VH comprising the amino acid sequence shown in SEQ ID NO:55 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO:55; and a VL comprising the amino acid sequence shown in SEQ ID NO:67 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO:67.
  • a disease associated with the LIGHT signaling pathway e.g., an autoimmune disease and/or an inflammatory disease
  • the anti-LIGHT antibody described herein is a full-length anti-LIGHT antibody comprising an IgG1 or IgG4 constant region.
  • the IgG1 is human IgG1.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:74.
  • the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:75.
  • the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO:76.
  • the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO:77.
  • a method for treating an individual suffering from a disease associated with a LIGHT signaling pathway comprising administering to the individual an effective amount of a pharmaceutical composition comprising an anti-LIGHT antibody (e.g., a full-length anti-LIGHT antibody), wherein the antibody comprises: a heavy chain variable domain ( VH ), the VH comprising: a HC-CDR1 comprising an amino acid sequence of SEQ ID NO:3, a HC-CDR2 comprising an amino acid sequence of SEQ ID NO:11, and a HC-CDR3 comprising an amino acid sequence of SEQ ID NO:18, or a variant of the VH comprising substitutions of up to about 5 amino acids in its HC-CDRs; and a light chain variable domain ( VL ), the VL comprising: a LC-CDR1 comprising an amino acid sequence of SEQ ID NO:26, a LC-CDR2
  • the anti-LIGHT antibody is a full-length antibody. In some embodiments, the full-length anti-LIGHT antibody is an IgG1 or IgG4 antibody.
  • the disease or condition is selected from, for example, inflammatory bowel disease (IBD), Crohn's disease, Disease, ulcerative colitis, ankylosing spondylitis, atopic dermatitis, rheumatoid arthritis, bronchiolitis, transplant rejection, allograft rejection, graft-versus-host disease (GVHD), asthma, eosinophilic esophagitis, acute respiratory distress syndrome (ARDS), chronic heart failure, chronic obstructive pulmonary disease (COPD), septic shock, fibrotic diseases, skin fibrosis, idiopathic pulmonary fibrosis, renal fibrosis, chronic kidney disease, systemic sclerosis, multiple sclerosis, Sjögren's syndrome, lupus, airway inflammation, psoriasis,
  • IBD inflammatory bowel
  • a method for treating an individual suffering from a disease associated with the LIGHT signaling pathway comprising administering to the individual an effective amount of a composition comprising an anti-LIGHT antibody, wherein the antibody comprises: a VH comprising the amino acid sequence shown in SEQ ID NO:56 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO:56; and a VL comprising the amino acid sequence shown in SEQ ID NO:68 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO:68.
  • a disease associated with the LIGHT signaling pathway e.g., an autoimmune disease and/or an inflammatory disease
  • the anti-LIGHT antibody described herein is a full-length anti-LIGHT antibody comprising an IgG1 or IgG4 constant region.
  • the IgG1 is human IgG1.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:74.
  • the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:75.
  • the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO:76.
  • the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO:77.
  • a method for treating an individual suffering from a disease associated with a LIGHT signaling pathway comprising administering to the individual an effective amount of a pharmaceutical composition comprising an anti-LIGHT antibody (e.g., a full-length anti-LIGHT antibody), wherein the antibody comprises: a heavy chain variable domain ( VH ), the VH comprising: a HC-CDR1 comprising the amino acid sequence of SEQ ID NO:3, a HC-CDR2 comprising the amino acid sequence of SEQ ID NO:11, and a HC-CDR3 comprising the amino acid sequence of SEQ ID NO:18, or a variant of the VH comprising substitutions of up to about 5 amino acids in its HC-CDRs; and a light chain variable domain ( VL ), the VL comprising: a LC-CDR1 comprising the amino acid sequence of SEQ ID NO:26, a LC-CDR2
  • the anti-LIGHT antibody is a full-length antibody. In some embodiments, the full-length anti-LIGHT antibody is an IgG1 or IgG4 antibody.
  • the disease or condition is selected from, for example, inflammatory bowel disease (IBD), Crohn's disease, ulcerative colitis, ankylosing spondylitis, atopic dermatitis, rheumatoid arthritis, bronchiolitis, transplant rejection, allograft rejection, graft-versus-host disease (GVHD), asthma, eosinophilic esophagitis, acute respiratory distress syndrome (ARDS), chronic heart failure, chronic obstructive pulmonary disease (COPD), septic shock, fibrotic disease, skin fibrosis, idiopathic pulmonary fibrosis, renal fibrosis, chronic kidney disease, systemic sclerosis, multiple sclerosis, Sjögren's syndrome, lupus, airway inflammation, psoriasis, hepati
  • IBD inflammatory
  • a method for treating an individual suffering from a disease associated with the LIGHT signaling pathway comprising administering to the individual an effective amount of a composition comprising an anti-LIGHT antibody, wherein the antibody comprises: a VH comprising the amino acid sequence shown in SEQ ID NO:57 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO:57; and a VL comprising the amino acid sequence shown in SEQ ID NO:69 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO:69.
  • a disease associated with the LIGHT signaling pathway e.g., an autoimmune disease and/or an inflammatory disease
  • the anti-LIGHT antibody described herein is a full-length anti-LIGHT antibody comprising an IgG1 or IgG4 constant region.
  • the IgG1 is human IgG1.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:74.
  • the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:75.
  • the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO:76.
  • the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO:77.
  • a method for treating an individual suffering from a disease associated with a LIGHT signaling pathway comprising administering to the individual an effective amount of a pharmaceutical composition comprising an anti-LIGHT antibody (e.g., a full-length anti-LIGHT antibody), wherein the antibody comprises: a heavy chain variable domain ( VH ), the VH comprising: a HC-CDR1 comprising the amino acid sequence of SEQ ID NO:4, a HC-CDR2 comprising the amino acid sequence of SEQ ID NO:12, and a HC-CDR3 comprising the amino acid sequence of SEQ ID NO:19, or a variant of the VH comprising substitutions of up to about 5 amino acids in its HC-CDRs; and a light chain variable domain ( VL ), the VL comprising: a LC-CDR1 comprising the amino acid sequence of SEQ ID NO:27, a LC-CDR2
  • the anti-LIGHT antibody is a full-length antibody. In some embodiments, the full-length anti-LIGHT antibody is an IgG1 or IgG4 antibody.
  • the disease or condition is selected from, for example, inflammatory bowel disease (IBD), Crohn's disease, ulcerative colitis, ankylosing spondylitis, atopic dermatitis, rheumatoid arthritis, bronchiolitis, transplant rejection, allograft rejection, graft-versus-host disease (GVHD), asthma, eosinophilic esophagitis, acute respiratory distress syndrome (ARDS), chronic heart failure, chronic obstructive pulmonary disease (COPD), septic shock, fibrotic disease, skin fibrosis, idiopathic pulmonary fibrosis, renal fibrosis, chronic kidney disease, systemic sclerosis, multiple sclerosis, Sjögren's syndrome, lupus, airway inflammation, psoriasis, hepati
  • IBD inflammatory
  • a method for treating an individual suffering from a disease associated with the LIGHT signaling pathway comprising administering to the individual an effective amount of a composition comprising an anti-LIGHT antibody, wherein the antibody comprises: a VH comprising the amino acid sequence of SEQ ID NO: 58 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 58; and a VL comprising the amino acid sequence of SEQ ID NO: The amino acid sequence shown in NO:70 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO:70.
  • a disease associated with the LIGHT signaling pathway e.g., an autoimmune disease and/or an inflammatory disease
  • the anti-LIGHT antibody described herein is a full-length anti-LIGHT antibody comprising an IgG1 or IgG4 constant region.
  • the IgG1 is human IgG1.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:74.
  • the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:75.
  • the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO:76.
  • the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO:77.
  • a method for treating an individual suffering from a disease associated with a LIGHT signaling pathway comprising administering to the individual an effective amount of a pharmaceutical composition comprising an anti-LIGHT antibody (e.g., a full-length anti-LIGHT antibody), wherein the antibody comprises: a heavy chain variable domain ( VH ), the VH comprising: a HC-CDR1 comprising an amino acid sequence of SEQ ID NO:5, a HC-CDR2 comprising an amino acid sequence of SEQ ID NO:13, and a HC-CDR3 comprising an amino acid sequence of SEQ ID NO:20, or a variant of the VH comprising substitutions of up to about 5 amino acids in its HC-CDRs; and a light chain variable domain ( VL ), the VL comprising: a LC-CDR1 comprising an amino acid sequence of SEQ ID NO:28, a LC-CDR2
  • the anti-LIGHT antibody is a full-length antibody. In some embodiments, the full-length anti-LIGHT antibody is an IgG1 or IgG4 antibody.
  • the disease or condition is selected from, for example, inflammatory bowel disease (IBD), Crohn's disease, ulcerative colitis, ankylosing spondylitis, atopic dermatitis, rheumatoid arthritis, bronchiolitis, transplant rejection, allograft rejection, graft-versus-host disease (GVHD), asthma, eosinophilic esophagitis, acute respiratory distress syndrome (ARDS), chronic heart failure, chronic obstructive pulmonary disease (COPD), septic shock, fibrotic disease, skin fibrosis, idiopathic pulmonary fibrosis, renal fibrosis, chronic kidney disease, systemic sclerosis, multiple sclerosis, Sjögren's syndrome, lupus, airway inflammation, psoriasis, hepati
  • IBD inflammatory
  • a method for treating an individual suffering from a disease associated with the LIGHT signaling pathway comprising administering to the individual an effective amount of a composition comprising an anti-LIGHT antibody, wherein the antibody comprises: a VH comprising the amino acid sequence shown in SEQ ID NO:59 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO:59; and a VL comprising the amino acid sequence shown in SEQ ID NO:71 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO:71.
  • a disease associated with the LIGHT signaling pathway e.g., an autoimmune disease and/or an inflammatory disease
  • the anti-LIGHT antibody described herein is a full-length anti-LIGHT antibody comprising an IgG1 or IgG4 constant region.
  • the IgG1 is human IgG1.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 74.
  • the heavy chain constant region comprises or consists of
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 75.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 76.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 77.
  • a method for treating an individual having a disease associated with a LIGHT signaling pathway comprising administering to the individual an effective amount of a pharmaceutical composition comprising an anti-LIGHT antibody (e.g., a full-length anti-LIGHT antibody), wherein the antibody comprises: a heavy chain complementary determining region (HC-CDR) 1 comprising DHIMN (SEQ ID NO: 6); a HC-CDR2 comprising RIYPVSGETNYNQKFMG (SEQ ID NO: 14); and a HC-CDR3 comprising GSYYWNAMDY (SEQ ID NO: 21); and a light chain variable domain ( VL ), the VL comprising: a light chain complementary determining region (LC-CDR) 1 comprising KASQSVDFDGDSYMN (SEQ ID NO: 29) or KASQSVDFDGESYMN (SEQ ID NO: 83); a
  • the anti-LIGHT antibody is a full-length antibody. In some embodiments, the full-length anti-LIGHT antibody is an IgG1 or IgG4 antibody.
  • the disease or condition is selected from, for example, inflammatory bowel disease (IBD), Crohn's disease, ulcerative colitis, ankylosing spondylitis, atopic dermatitis, rheumatoid arthritis, bronchiolitis, transplant rejection, allograft rejection, graft-versus-host disease (GVHD), asthma, eosinophilic esophagitis, acute respiratory distress syndrome (ARDS), chronic heart failure, chronic obstructive pulmonary disease (COPD), septic shock, fibrotic disease, skin fibrosis, idiopathic pulmonary fibrosis, renal fibrosis, chronic kidney disease, systemic sclerosis, multiple sclerosis, Sjögren's syndrome, lupus, airway inflammation, psoriasis
  • IBD inflammatory bowel disease
  • a method for treating an individual suffering from a disease associated with a LIGHT signaling pathway comprising administering to the individual an effective amount of a pharmaceutical composition comprising an anti-LIGHT antibody (e.g., a full-length anti-LIGHT antibody), wherein the antibody comprises: a heavy chain variable domain ( VH ), the VH comprising: a HC-CDR1 comprising the amino acid sequence of SEQ ID NO:6, a HC-CDR2 comprising the amino acid sequence of SEQ ID NO:14, and a HC-CDR3 comprising the amino acid sequence of SEQ ID NO:21, or a variant of the VH comprising substitutions of up to about 5 amino acids in its HC-CDRs; and a light chain variable domain ( VL ), the VL comprising: a LC-CDR1 comprising the amino acid sequence shown in any one of SEQ ID NOs:29 or 83, a
  • the anti-LIGHT antibody is a full-length antibody. In some embodiments, the full-length anti-LIGHT antibody is an IgG1 or IgG4 antibody.
  • the disease or condition is selected from, for example, inflammatory bowel disease (IBD), Crohn's disease, ulcerative colitis, ankylosing spondylitis, atopic dermatitis, rheumatoid arthritis, bronchiolitis, transplant rejection, allograft rejection, graft-versus-host disease (GVHD), asthma, eosinophilic esophagitis, acute respiratory distress syndrome (ARDS), chronic heart failure, chronic obstructive pulmonary disease (COPD), septic shock, fibrotic disease, skin fibrosis, idiopathic pulmonary fibrosis, renal fibrosis, chronic kidney disease, systemic sclerosis, multiple sclerosis, Sjögren's syndrome, lupus, airway inflammation, psoriasis, hepati
  • IBD inflammatory
  • a method for treating an individual suffering from a disease associated with the LIGHT signaling pathway comprising administering to the individual an effective amount of a composition comprising an anti-LIGHT antibody, wherein the antibody comprises: a VH comprising an amino acid sequence as shown in any one of SEQ ID NOs:60, 84-85 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence as shown in any one of SEQ ID NOs:60, 84-85; and a VL comprising an amino acid sequence as shown in any one of SEQ ID NOs:72, 86-91 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence as shown in any one of SEQ ID NOs:72, 86-91.
  • the antibody comprises: a VH comprising an amino acid sequence as shown in any one of SEQ ID NOs:60, 84-85 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence as shown in any one of S
  • the anti-LIGHT antibody described herein is a full-length anti-LIGHT antibody comprising an IgG1 or IgG4 constant region.
  • the IgG1 is human IgG1.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:74.
  • the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:75.
  • the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO:76.
  • the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO:77.
  • a method for treating an individual suffering from a disease associated with a LIGHT signaling pathway comprising administering to the individual an effective amount of a pharmaceutical composition comprising an anti-LIGHT antibody (e.g., a full-length anti-LIGHT antibody), wherein the antibody comprises: a heavy chain variable domain ( VH ), the VH comprising: a HC-CDR1 comprising the amino acid sequence of SEQ ID NO:6, a HC-CDR2 comprising the amino acid sequence of SEQ ID NO:14, and a HC-CDR3 comprising the amino acid sequence of SEQ ID NO:21, or a variant of the VH comprising substitutions of up to about 5 amino acids in its HC-CDRs; and a light chain variable domain ( VL ), the VL comprising: a LC-CDR1 comprising the amino acid sequence of SEQ ID NO:29, a LC-CDR2 comprising the
  • the anti-LIGHT antibody is a full-length antibody. In some embodiments, the full-length anti-LIGHT antibody is an IgG1 or IgG4 antibody.
  • the disease or condition is selected from, for example, inflammatory bowel disease (IBD), Crohn's disease, ulcerative colitis, ankylosing spondylitis, atopic dermatitis, rheumatoid arthritis, bronchiolitis, transplant rejection, allograft rejection, graft-versus-host disease (GVHD), asthma, eosinophilic esophagitis, acute respiratory distress syndrome (ARDS), chronic heart failure, chronic obstructive pulmonary disease (COPD), septic shock, fibrotic disease, skin fibrosis, idiopathic pulmonary fibrosis, renal fibrosis, chronic kidney disease, systemic sclerosis, multiple sclerosis, Sjögren's syndrome, lupus, airway inflammation, psoriasis, hepati
  • IBD inflammatory
  • a method for treating an individual suffering from a disease associated with the LIGHT signaling pathway comprising administering to the individual an effective amount of a composition comprising an anti-LIGHT antibody, wherein the antibody comprises: a VH comprising the amino acid sequence of SEQ ID NO: 60 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 60; and a VL comprising the amino acid sequence of SEQ ID NO: 60. NO:72 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO:72.
  • a disease associated with the LIGHT signaling pathway e.g., an autoimmune disease and/or an inflammatory disease
  • the anti-LIGHT antibody described herein is a full-length anti-LIGHT antibody comprising an IgG1 or IgG4 constant region.
  • the IgG1 is human IgG1.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:74.
  • the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:75.
  • the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO:76.
  • the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO:77.
  • the anti-LIGHT antibodies described herein comprise: a VH comprising the amino acid sequence of SEQ ID NO: 84 or a variant thereof having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 84; and a VL comprising the amino acid sequence of SEQ ID NO: 86 or a variant thereof having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 86.
  • the anti-LIGHT antibodies described herein are full-length anti-LIGHT antibodies comprising an IgG1 or IgG4 constant region.
  • the IgG1 is a human IgG1.
  • the IgG4 is a human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 74. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 75. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 77.
  • the anti-LIGHT antibodies described herein comprise: a VH comprising the amino acid sequence of SEQ ID NO: 85 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 85; and a VL comprising the amino acid sequence of SEQ ID NO: 87 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 87.
  • the anti-LIGHT antibodies described herein are full-length anti-LIGHT antibodies comprising an IgG1 or IgG4 constant region.
  • the IgG1 is a human IgG1.
  • the IgG4 is a human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 74. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 75. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 77.
  • the anti-LIGHT antibodies described herein comprise: a VH comprising the amino acid sequence of SEQ ID NO: 84 or a variant thereof having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 84; and a VL comprising the amino acid sequence of SEQ ID NO: 88 or a variant thereof having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 88.
  • the anti-LIGHT antibodies described herein are full-length anti-LIGHT antibodies comprising an IgG1 or IgG4 constant region.
  • the IgG1 is a human IgG1.
  • the IgG4 is a human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 74. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 75. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 77.
  • a method for treating an individual suffering from a disease associated with a LIGHT signaling pathway comprising administering to the individual an effective amount of a composition comprising an anti-LIGHT antibody, wherein the antibody comprises: a VH , wherein the VH comprises: a HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 6, a HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 14, and a HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 21, or or a variant of said V H comprising at most about 5 amino acid substitutions in its HC-CDRs; and V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:83, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:35, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:43, or a variant of said V
  • the anti-LIGHT antibodies described herein comprise: a VH comprising the amino acid sequence of SEQ ID NO: 84 or a variant thereof having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 84; and a VL comprising the amino acid sequence of SEQ ID NO: 89 or a variant thereof having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 89.
  • the anti-LIGHT antibodies described herein are full-length anti-LIGHT antibodies comprising an IgG1 or IgG4 constant region.
  • the IgG1 is a human IgG1.
  • the IgG4 is a human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 74. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 75. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 77.
  • the anti-LIGHT antibodies described herein comprise: a VH comprising the amino acid sequence of SEQ ID NO: 85 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 85; and a VL comprising the amino acid sequence of SEQ ID NO: 90 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 90.
  • the anti-LIGHT antibodies described herein are full-length anti-LIGHT antibodies comprising an IgG1 or IgG4 constant region.
  • the IgG1 is a human IgG1.
  • the IgG4 is a human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 74. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 75. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 77.
  • the anti-LIGHT antibodies described herein comprise: a VH comprising the amino acid sequence of SEQ ID NO: 84 or a variant thereof having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 84; and a VL comprising the amino acid sequence of SEQ ID NO: 91 or a variant thereof having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 91.
  • the anti-LIGHT antibodies described herein are full-length anti-LIGHT antibodies comprising an IgG1 or IgG4 constant region.
  • the IgG1 is a human IgG1.
  • the IgG4 is a human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 74. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 75. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 77.
  • a method for treating an individual suffering from a disease associated with a LIGHT signaling pathway comprising administering to the individual an effective amount of a pharmaceutical composition comprising an anti-LIGHT antibody (e.g., a full-length anti-LIGHT antibody), wherein the antibody comprises: a heavy chain variable domain ( VH ), the VH comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO:7, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO:15, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO:22, or a variant of the VH comprising substitutions of up to about 5 amino acids in the HC-CDRs; and a light chain variable domain ( VL ), the VL comprising: an LC-CDR1 comprising an amino acid sequence of SEQ ID NO:13;
  • the anti-LIGHT antibody e.g., a full-length anti-LIGHT antibody
  • the antibody comprises: a heavy chain variable domain ( VH
  • the full-length anti-LIGHT antibody is an IgG1 or IgG4 antibody.
  • the disease or condition is selected from, for example, inflammatory bowel disease (IBD), Crohn's disease, ulcerative colitis, ankylosing spondylitis, atopic dermatitis, rheumatoid arthritis, bronchiolitis, transplant rejection, allograft rejection, graft-versus-host disease (GVHD), asthma, eosinophilic esophagitis, acute respiratory distress syndrome (ARDS), chronic heart failure, chronic obstructive pulmonary disease (COPD), septic shock, fibrotic diseases, skin fibrosis, idiopathic pulmonary fibrosis, renal fibrosis, chronic kidney disease, systemic sclerosis, multiple sclerosis, Sjögren's syndrome, lupus, airway inflammation, psoriasis, hepatitis, celiac disease, primary biliary cirrhosis
  • IBD inflammatory
  • a method for treating an individual suffering from a disease associated with the LIGHT signaling pathway comprising administering to the individual an effective amount of a composition comprising an anti-LIGHT antibody, wherein the antibody comprises: a VH comprising an amino acid sequence as shown in any one of SEQ ID NOs:61, 92-94 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence as shown in any one of SEQ ID NOs:61, 92-94; and a VL comprising an amino acid sequence as shown in any one of SEQ ID NOs:73, 95-99 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence as shown in any one of SEQ ID NOs:73, 95-99.
  • a disease associated with the LIGHT signaling pathway e.g., an autoimmune disease and/or an inflammatory disease
  • the anti-LIGHT antibody described herein is a full-length anti-LIGHT antibody comprising an IgG1 or IgG4 constant region.
  • the IgG1 is human IgG1.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:74.
  • the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:75.
  • the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO:76.
  • the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO:77.
  • a method for treating an individual suffering from a disease associated with a LIGHT signaling pathway comprising administering to the individual an effective amount of a composition comprising an anti-LIGHT antibody, wherein the antibody comprises: a VH comprising an amino acid sequence as shown in SEQ ID NO: 61 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence as shown in SEQ ID NO: 61; and a VL comprising an amino acid sequence as shown in SEQ ID NO: 73 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence as shown in SEQ ID NO: 73.
  • a disease associated with a LIGHT signaling pathway e.g., an autoimmune disease and/or an inflammatory disease
  • the anti-LIGHT antibody described herein is a full-length anti-LIGHT antibody comprising an IgG1 or IgG4 constant region.
  • the IgG1 is a human IgG1.
  • the IgG4 is a human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 74.
  • the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 75.
  • the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 76.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:77.
  • a method for treating an individual suffering from a disease associated with the LIGHT signaling pathway comprising administering to the individual an effective amount of a combination comprising an anti-LIGHT antibody
  • the anti- LIGHT antibody described herein is a full-length anti-LIGHT antibody comprising an IgG1 or IgG4 constant region.
  • the IgG1 is a human IgG1.
  • the IgG4 is a human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:74.
  • the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:75. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO:76. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO:77.
  • a method for treating an individual with a disease associated with a LIGHT signaling pathway comprising administering to the individual an effective amount of a composition comprising an anti-LIGHT antibody, wherein the antibody comprises: a VH comprising an amino acid sequence of SEQ ID NO: 93 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 93; and a VL comprising an amino acid sequence of SEQ ID NO: 96 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 96.
  • a disease associated with a LIGHT signaling pathway e.g., an autoimmune disease and/or an inflammatory disease
  • the anti-LIGHT antibody described herein is a full-length anti-LIGHT antibody comprising an IgG1 or IgG4 constant region.
  • the IgG1 is a human IgG1.
  • the IgG4 is a human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 74.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 75.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 76.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 77.
  • a method for treating an individual with a disease associated with a LIGHT signaling pathway comprising administering to the individual an effective amount of a composition comprising an anti-LIGHT antibody, wherein the antibody comprises: a VH comprising an amino acid sequence of SEQ ID NO: 92 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 92; and a VL comprising an amino acid sequence of SEQ ID NO: 96 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 96.
  • a disease associated with a LIGHT signaling pathway e.g., an autoimmune disease and/or an inflammatory disease
  • a method for treating an individual suffering from a disease associated with the LIGHT signaling pathway comprising administering to the individual an effective amount of a composition comprising an anti-LIGHT antibody, wherein the antibody comprises: a VH comprising an amino acid sequence of SEQ ID NO: 94 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 94; and a VL comprising an amino acid sequence of SEQ ID NO: 97 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 97.
  • a disease associated with the LIGHT signaling pathway e.g., an autoimmune disease and/or an inflammatory disease
  • the anti-LIGHT antibody described herein is a full-length anti-LIGHT antibody comprising an IgG1 or IgG4 constant region.
  • the IgG1 is human IgG1.
  • the IgG4 is human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:74.
  • the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO:75.
  • the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO:76.
  • the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO:77.
  • a method for treating an individual suffering from a disease associated with a LIGHT signaling pathway comprising administering to the individual an effective amount of a composition comprising an anti-LIGHT antibody, wherein the antibody comprises: a VH comprising an amino acid sequence of SEQ ID NO: 94 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 94; and a VL comprising an amino acid sequence of SEQ ID NO: 98 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 98.
  • a disease associated with a LIGHT signaling pathway e.g., an autoimmune disease and/or an inflammatory disease
  • the anti-LIGHT antibody described herein is a full-length anti-LIGHT antibody comprising an IgG1 or IgG4 constant region.
  • the IgG1 is a human IgG1.
  • the IgG4 is a human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 74.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 75.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 76.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 77.
  • a method for treating an individual suffering from a disease associated with a LIGHT signaling pathway comprising administering to the individual an effective amount of a composition comprising an anti-LIGHT antibody, wherein the antibody comprises: a VH comprising an amino acid sequence of SEQ ID NO: 93 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 93; and a VL comprising an amino acid sequence of SEQ ID NO: 98 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 98.
  • a disease associated with a LIGHT signaling pathway e.g., an autoimmune disease and/or an inflammatory disease
  • the anti-LIGHT antibody described herein is a full-length anti-LIGHT antibody comprising an IgG1 or IgG4 constant region.
  • the IgG1 is a human IgG1.
  • the IgG4 is a human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 74.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 75.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 76.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 77.
  • a method for treating an individual with a disease associated with a LIGHT signaling pathway comprising administering to the individual an effective amount of a composition comprising an anti-LIGHT antibody, wherein the antibody comprises: a VH comprising an amino acid sequence of SEQ ID NO: 92 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 92; and a VL comprising an amino acid sequence of SEQ ID NO: 98 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 98.
  • the anti-LIGHT antibody described herein is a full-length anti-LIGHT antibody comprising an IgG1 or IgG4 constant region.
  • the IgG1 is a human IgG1.
  • the IgG4 is a human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 74.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 75.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 76.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 77.
  • a method for treating an individual suffering from a disease associated with a LIGHT signaling pathway comprising administering to the individual an effective amount of a composition comprising an anti-LIGHT antibody, wherein the antibody comprises: a VH comprising an amino acid sequence of SEQ ID NO: 94 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 94; and a VL comprising an amino acid sequence of SEQ ID NO: 99 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 99.
  • a disease associated with a LIGHT signaling pathway e.g., an autoimmune disease and/or an inflammatory disease
  • the anti-LIGHT antibody described herein is a full-length anti-LIGHT antibody comprising an IgG1 or IgG4 constant region.
  • the IgG1 is a human IgG1.
  • the IgG4 is a human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 74.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 75.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 76.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 77.
  • a method for treating an individual suffering from a disease associated with a LIGHT signaling pathway comprising administering to the individual an effective amount of a composition comprising an anti-LIGHT antibody, wherein the antibody comprises: a VH comprising an amino acid sequence of SEQ ID NO: 92 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 92; and a VL comprising an amino acid sequence of SEQ ID NO: 99 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 99.
  • a disease associated with a LIGHT signaling pathway e.g., an autoimmune disease and/or an inflammatory disease
  • the anti-LIGHT antibody described herein is a full-length anti-LIGHT antibody comprising an IgG1 or IgG4 constant region.
  • the IgG1 is a human IgG1.
  • the IgG4 is a human IgG4.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 74.
  • the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 75.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 76.
  • the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 77.
  • the individual is a mammal (e.g., human, non-human primate, rat, mouse, cattle, horse, pig, sheep, goat, dog, cat, etc.). In some embodiments, the individual is a human. In some embodiments, the individual is a clinical patient, a clinical trial volunteer, an experimental animal, etc. In some embodiments, the individual is less than 60 years old (including, for example, less than 50, 40, 30, 25, 20, 15 or 10 years old). In some embodiments, the individual is greater than 60 years old (including, for example, greater than 70, 80, 90 or 100 years old).
  • the individual is diagnosed as or is susceptible to one or more diseases or conditions described herein (e.g., autoimmune diseases and/or inflammatory diseases) from a genetic perspective.
  • the individual has one or more risk factors associated with one or more diseases or conditions described herein.
  • the present application provides a method of delivering an anti-LIGHT antibody (e.g., any anti-LIGHT antibody described herein, e.g., an isolated anti-LIGHT antibody) to cells expressing LIGHT on their surface in an individual, the method comprising administering a composition comprising the anti-LIGHT antibody to the individual.
  • an anti-LIGHT antibody e.g., any anti-LIGHT antibody described herein, e.g., an isolated anti-LIGHT antibody
  • autoimmune diseases and/or inflammatory diseases or any other diseases showing abnormal expression of LIGHT and clinical descriptions of these diseases are known in the art. Such methods include, but are not limited to, immunohistochemistry, PCR, and fluorescence in situ hybridization (FISH).
  • FISH fluorescence in situ hybridization
  • the anti-LIGHT antibody e.g., full-length anti-LIGHT antibody
  • composition described herein is used in combination with a second, third or fourth agent (including, for example, steroids, non-steroidal anti-inflammatory drugs (NSAIDS) (e.g., salicylates, propionic acid derivatives, acetic acid derivatives, enolic acid derivatives, o-aminophenyl acid derivatives, selective COX-2 inhibitors and sulfonanilides), glucocorticoids (e.g., Cortisol, cortisone, prednisone, prednisolone, dexamethasone, betamethasone, triamcinolone, etc.), cytostatics (e.g., alkylating agents, antimetabolites, methotrexate, thiopurine, mercaptopurine or cytotoxic antibiotics), TNF inhibitors, IL-12 inhibitors, IL-23 inhibitors, ⁇ 4 ⁇ 7 integrin
  • NSAIDS non
  • the dosage of the anti-LIGHT antibody (e.g., isolated anti-LIGHT antibody) composition administered to an individual may vary depending on the specific composition, mode of administration, and type of disease being treated.
  • the amount of the composition e.g., a composition comprising an anti-LIGHT antibody
  • an objective response e.g., a partial response or a complete response
  • the amount of the anti-LIGHT antibody composition is sufficient to produce a complete response in an individual.
  • the amount of the anti-LIGHT antibody composition is sufficient to produce a partial response in an individual.
  • the dosage of the anti-LIGHT antibody composition (e.g., when administered alone) is sufficient to produce a total response rate of more than 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 64%, 65%, 70%, 75%, 80%, 85% or 90% in a population of individuals treated with an anti-LIGHT antibody composition.
  • the response of an individual to the treatment methods described herein can be determined, for example, by an ACQ5 score.
  • the amount of the composition is sufficient to extend the progression-free survival of the individual. In some embodiments, the amount of the composition is sufficient to extend the overall survival of the individual. In some embodiments, in a population of individuals treated with an anti-LIGHT antibody composition, the amount of the composition (e.g., when administered alone) is sufficient to produce a clinical benefit greater than 50%, 60%, 70%, or 77%.
  • the amount of a composition refers to an amount sufficient to control symptoms and reduce the risk of exacerbation of the disease before treatment or compared with the corresponding activity of other subjects not receiving treatment.
  • the magnitude of the therapeutic effect can be measured by standard methods, such as in vitro assays of purified enzymes, cell-based assays, animal models, or human trials.
  • the amount of the anti-LIGHT antibody (e.g., a full-length anti-LIGHT antibody) in the composition is below a level that causes a toxic effect (i.e., an effect above a clinically acceptable toxicity level), or is at a level at which potential side effects can be controlled or tolerated.
  • the amount of the composition is close to the maximum tolerated dose (MTD) of the composition. In some embodiments, the amount of the composition is higher than 80%, 90%, 95% or 98% of the MTD.
  • the content of the anti-LIGHT antibody (eg, full-length anti-LIGHT antibody) in the composition is in the range of 0.001 ⁇ g to 1000 ⁇ g.
  • the effective amount of the anti-LIGHT antibody (eg, full-length anti-LIGHT antibody) in the composition is in the range of 0.1 ⁇ g/kg to 100 mg/kg, calculated based on body weight.
  • Anti-LIGHT antibody compositions can be administered to individuals (such as humans) by a variety of routes, including, for example, intravenous injection, intraarterial administration, intraperitoneal injection, intrapulmonary administration, oral administration, inhalation administration, intravascular administration, intramuscular injection, intratracheal administration, subcutaneous injection, intraocular administration, intrathecal administration, mucosal administration or transdermal administration.
  • a sustained-release formulation of the composition is used.
  • the composition is administered intravenously.
  • the composition is administered by artery.
  • the composition is administered intraperitoneally.
  • the composition is administered intrahepatically.
  • the composition is administered by hepatic artery infusion.
  • the composition is administered to a site away from the first lesion.
  • a product comprising a substance that can be used to treat a disease associated with the LIGHT signaling pathway (e.g., an autoimmune disease and/or an inflammatory disease), or for delivering an anti-LIGHT antibody (e.g., a full-length anti-LIGHT antibody) to cells expressing LIGHT on the surface.
  • the product may include a container and a label or package insert on or with the container. Suitable containers include, for example, bottles, vials, syringes, etc.
  • the container can be made of a variety of materials, such as glass or plastic.
  • the container contains a composition that can effectively treat the disease or condition described herein, and has a sterile port (e.g., the container can be an intravenous infusion bag or a vial with a hypodermic injection needle that can pierce the lid).
  • a sterile port e.g., the container can be an intravenous infusion bag or a vial with a hypodermic injection needle that can pierce the lid.
  • At least one active substance in the composition is the anti-LIGHT antibody described in the present application.
  • the label or package insert indicates the specific condition that the composition can be used to treat.
  • the label or package insert further includes instructions for administering the anti-LIGHT antibody composition to the patient. Products and kits including combined therapies are within the scope of consideration herein.
  • Package inserts refer to instructions typically included in commercial packages of therapeutic products, which contain information about indications, usage, dosage, administration, contraindications and/or warnings related to the use of these therapeutic products.
  • the package insert indicates that the composition can be used to treat diseases associated with the LIGHT signaling pathway (e.g., autoimmune diseases and/or inflammatory diseases).
  • the package insert indicates that the composition can be used to treat the following diseases, including inflammatory bowel disease (IBD), Crohn's disease, ulcerative colitis, ankylosing spondylitis, atopic dermatitis, rheumatoid arthritis, bronchiolitis, transplant rejection, allograft rejection, graft-versus-host disease (GVHD), asthma, eosinophilic esophagitis, acute respiratory distress syndrome (ARDS), chronic heart failure, chronic obstructive pulmonary disease (COPD), septic shock, fibrotic diseases, skin fibrosis, idiopathic pulmonary fibrosis, renal fibrosis, chronic kidney disease, systemic sclerosis, multiple sclerosis, Sjogren's syndrome, lupus, airway inflammation, psoriasis, hepatitis, celiac disease, primary biliary cirrhosis, autoimmune hemolytic anemia, autoimmune neonatal thrombocytopenia, i
  • IBD
  • the article of manufacture may further include a second container comprising a pharmaceutically acceptable buffer, such as bacteriostatic water for injection (BWFI), phosphate buffered saline, Ringer's solution or dextrose solution.
  • a pharmaceutically acceptable buffer such as bacteriostatic water for injection (BWFI), phosphate buffered saline, Ringer's solution or dextrose solution.
  • BWFI bacteriostatic water for injection
  • phosphate buffered saline such as phosphate buffered saline, Ringer's solution or dextrose solution.
  • Other materials required from a commercial and user perspective may also be included, including other buffers, diluents, filters, needles and syringes.
  • kits that can be used for various purposes, such as for treating diseases associated with the LIGHT signaling pathway (e.g., autoimmune diseases and/or inflammatory diseases), or for delivering anti-LIGHT antibodies (e.g., full-length anti-LIGHT antibodies) to cells expressing LIGHT on their surfaces, optionally in combination with a product.
  • the kit of the present application includes one or more containers containing an anti-LIGHT antibody.
  • LIGHT antibody composition (or single dose form and/or product), and in some embodiments, further comprises another agent (e.g., an agent described herein) and/or instructions for use consistent with any of the methods described herein.
  • the kit may further include a description of selecting an individual suitable for treatment.
  • the instructions for use included in the kit in this application are typically written instructions on a label or package insert (e.g., a paper sheet included in the kit), and machine-readable instructions (e.g., instructions on a magnetic or optical storage disc) are also acceptable.
  • the kit includes a composition comprising an anti-LIGHT antibody (e.g., a full-length anti-LIGHT antibody).
  • the kit includes: a) a composition comprising any anti-LIGHT antibody described herein, and b) at least one effective amount of other agents that can enhance the effect of the anti-LIGHT antibody (e.g., therapeutic effect, detection effect).
  • the kit includes: a) a composition comprising any anti-LIGHT antibody described herein, and b) instructions for use of administering an anti-LIGHT antibody composition to an individual for treating a disease associated with the LIGHT signaling pathway (e.g., an autoimmune disease and/or an inflammatory disease).
  • a disease associated with the LIGHT signaling pathway e.g., an autoimmune disease and/or an inflammatory disease.
  • the kit includes: a) a composition comprising any anti-LIGHT antibody described herein, and b) at least one effective amount of other agents that can enhance the effect of the anti-LIGHT antibody (e.g., therapeutic effect, detection effect) and c) instructions for use of administering an anti-LIGHT antibody composition and other substances to an individual for treating a disease associated with the LIGHT signaling pathway (e.g., an autoimmune disease and/or an inflammatory disease).
  • the anti-LIGHT antibody and other substances may be present in separate containers or in the same container.
  • the kit can include one particular composition or two or more compositions, wherein one composition includes an anti-LIGHT antibody and another composition includes another agent.
  • the kit comprises one (or a group) of nucleic acids encoding anti-LIGHT antibodies (e.g., full-length anti-LIGHT antibodies). In some embodiments, the kit comprises: a) one (or a group) of nucleic acids encoding anti-LIGHT antibodies (e.g., full-length anti-LIGHT antibodies), and b) a host cell expressing the nucleic acid (or a group of nucleic acids).
  • the kit comprises: a) one (or a group) of nucleic acids encoding anti-LIGHT antibodies (e.g., full-length anti-LIGHT antibodies), and b) instructions for use, suitable for: i) expressing anti-LIGHT antibodies in host cells, ii) preparing compositions comprising anti-LIGHT antibodies, and iii) administering compositions comprising anti-LIGHT antibodies to individuals to treat diseases associated with the LIGHT signaling pathway (e.g., autoimmune diseases and/or inflammatory diseases).
  • diseases associated with the LIGHT signaling pathway e.g., autoimmune diseases and/or inflammatory diseases.
  • the kit comprises: a) a nucleic acid (or a group of nucleic acids) encoding an anti-LIGHT antibody (e.g., a full-length anti-LIGHT antibody), b) a host cell expressing the nucleic acid (or a group of nucleic acids), and c) instructions for use, suitable for: i) expressing the anti-LIGHT antibody in the host cell, ii) preparing a composition comprising the anti-LIGHT antibody, and iii) administering the composition comprising the anti-LIGHT antibody to an individual to treat a disease associated with the LIGHT signaling pathway (e.g., an autoimmune disease and/or an inflammatory disease).
  • a disease associated with the LIGHT signaling pathway e.g., an autoimmune disease and/or an inflammatory disease.
  • the kit described in the present application is packaged in a suitable form.
  • suitable packaging includes, but is not limited to, vials, bottles, jars, flexible packages (e.g., sealed polyester film or plastic bags), etc.
  • the kit can optionally provide other components, such as buffer and instruction information. Therefore, the present application also provides products, which include vials, bottles, jars, flexible packages (e.g., sealed polyester film or plastic bags), etc.
  • kits for use of the anti-LIGHT antibody composition generally include information such as dosage, dosing cycle, and route of administration.
  • the container may be a unit dose, a bulk package (e.g., a multi-dose package), or a subunit dose.
  • a kit containing a sufficient dose of an anti-LIGHT antibody as described herein is provided to administer to an individual.
  • Long-term effective treatment such as one week, 8 days, 9 days, 10 days, 11 days, 12 days, 13 days, 2 weeks, 3 weeks, 4 weeks, 6 weeks, 8 weeks, 3 months, 4 months, 5 months, 7 months, 8 months, 9 months or longer.
  • the kit can also include multiple unit doses of anti-LIGHT antibodies, pharmaceutical compositions and instructions for use, and are packaged in quantities sufficient for storage and use in pharmacies, such as hospital pharmacies and compounding pharmacies.
  • LIGHT also known as TNFSF14, tumor necrosis factor superfamily member 14
  • HVEM herpes virus entry mediator, also known as TNFRSF14, CD270
  • LT ⁇ R lymphotoxin ⁇ receptor, lymphotoxin ⁇ receptor
  • the cDNA encoding human, cynomolgus monkey or mouse LIGHT is constructed into a mammalian cell expression vector by subcloning.
  • a His tag and/or an Fc tag and/or other tags commonly used by those skilled in the art are added to the N-terminus of the above cDNA to construct and express a fusion protein containing human, cynomolgus monkey or mouse LIGHT, such as His-human LIGHT (His-huLIGHT, SEQ ID NO: 79), hFc-human LIGHT (hFc-huLIGHT, SEQ ID NO: 80), His-cynomolgus monkey LIGHT (His-cynoLIGHT, SEQ ID NO: 81), and His-mouse LIGHT (His-musLIGHT, SEQ ID NO: 82).
  • His-human LIGHT His-huLIGHT, SEQ ID NO: 79
  • hFc-human LIGHT hFc-huLIGHT, SEQ ID
  • the above recombinant LIGHT proteins including hFc-huLIGHT, His-huLIGHT, His-cynoLIGHT, and His-musLIGHT, were expressed and purified.
  • the expression vector plasmids containing the above fusion protein genes were transfected into 293F cells, and the above cells were cultured at 37°C, 5% CO 2 , and 120 rpm for 5 days, and then the cell culture fluid was collected.
  • recombinant proteins with His tags were purified using a nickel column (Ni).
  • Ni nickel column
  • the specific operation was as follows: Immobilized metal affinity chromatography (IMAC) was performed using Ni-NTA (5 ml) from Changzhou Tiandi Renhe Biotechnology Co., Ltd. First, the nickel column was equilibrated with buffer A1 (1 ⁇ PBS, pH 7.4) at a flow rate of 150 cm/h, and the pH of the culture supernatant was adjusted to 7.2-7.4 at room temperature, and the sample was loaded at a flow rate of 5 ml/min. Subsequently, the column was equilibrated again with 6 column volumes of A1 buffer at a flow rate of 5 ml/min.
  • IMAC Immobilized metal affinity chromatography
  • the impurities were washed with 6 column volumes of A2 buffer (1 ⁇ PBS containing 30 mM imidazole, pH 7.4) at a flow rate of 5 ml/min, and finally eluted with 10 column volumes of B buffer (1 ⁇ PBS containing 0.25 M imidazole, pH 7.4), and the eluate was collected and concentrated with an ultrafiltration tube with a suitable molecular weight cutoff to PBS.
  • recombinant proteins with Fc tags were purified using a Protein A affinity column.
  • the specific operation was as follows: First, 6 column volumes of PBS buffer (containing 0.15M NaCl, pH7.4) were used to equilibrate the Protein A column at a flow rate of 150 cm/h (flow rate 5 ml/min). The culture supernatant (adjusted to pH 7.2-7.4) was passed through the column at a flow rate of 150 cm/h (flow rate 5 ml/min). After further equilibration of the column, 6 column volumes of 0.1M glycine buffer (containing 0.15M NaCl, pH3.2) were used to elute and collect The pH value of the eluent was adjusted to neutral. The target protein solution was replaced with PBS buffer using an ultrafiltration concentration tube, and the target protein concentration was determined using a BCA protein quantification kit after ultrafiltration and concentration.
  • scFv antibody phage display library His-huLIGHT was used as an antigen to immunize 6-8 week old BALB/c mice with equal parts (v/v) of adjuvant. The sera of immunized mice were collected, and the total IgG titer in the sera of immunized mice was detected by ELISA. After several rounds of immunization, the phage display library was established using the spleen of mice.
  • spleen of immunized mice was taken, RNA was extracted, cDNA was obtained by reverse transcription, VH and VK specific primers were used to amplify VH and VK fragments, and after gel recovery and purification, VH and VK were connected to construct scFv, which was cloned into the phage display vector pDAN3X, and transformed into TG1 phage display electroporation competent cells after connection to obtain the scFv antibody phage display library.
  • the sequenced VL and VH sequences of the mouse anti-LIGHT antibody were constructed into the eukaryotic expression vectors pTTa1-L (containing the ⁇ constant region) and pTTa1-H4 (containing the human IgG4 heavy chain constant region), respectively.
  • the extracted plasmids expressing the light chain or heavy chain were co-transfected into 293F cells and cultured at 37°C, 8% CO2 , and 120 rpm for 6 days.
  • the culture fluid was purified using a protein A affinity chromatography column.
  • the protein A column was first equilibrated with 6 column volumes of PBS buffer (containing 0.15 M NaCl, pH 7.4) at a flow rate of 5 ml/min.
  • the culture supernatant (pH adjusted to 7.2-7.4) flowed through the column at a flow rate of 5 ml/min.
  • 6 column volumes of 0.1 M glycine buffer (containing 0.15 M NaCl, pH 3.2) were used for elution, the eluate was collected, and the pH was adjusted to neutral.
  • the IgG solution was replaced in PBS buffer using a desalting column, and the IgG concentration was measured after ultrafiltration and concentration to obtain a full-length chimeric anti-LIGHT antibody.
  • ELISA binding test The purified chimeric antibody was subjected to a binding test with human LIGHT protein to identify the binding activity of the candidate chimeric anti-LIGHT antibody with human LIGHT.
  • the purified His-huLIGHT was dissolved in PBS solution, coated on a 96-well plate at 0.1 ⁇ g/well, incubated overnight at 4°C, and washed 6 times with PBST solution. Add 1% BSA (PBS dissolved) blocking solution, block at 37°C for 1 hour, and wash 6 times with PBST solution.
  • the activity of anti-LIGHT antibody in blocking the binding of LIGHT to its receptor LT ⁇ R was detected by ELISA, and the IC 50 value was used as a standard to measure the neutralizing activity of candidate chimeric antibodies.
  • 100 ng/well of human LT ⁇ R-His (from Shutaishen) was coated on a 96-well plate, incubated at 4°C overnight, and washed 6 times with PBST solution.
  • 1% BSA (dissolved in PBS) blocking solution was added, blocked at 37°C for 1 hour, and washed 6 times with PBST solution.
  • the results are shown in Table 6.
  • the chimeric anti-LIGHT antibodies LT-m17, LT-m18, LT-m31, LT-m33, LT-m37, LT-m55, LT-m58, LT-m64, and LT-m85 can effectively block the binding of LIGHT to its receptor LT ⁇ R, and their neutralizing activities are better than those of the positive control antibody F19.
  • LIGHT not only binds to the LT ⁇ R receptor, but also binds to the HVEM receptor.
  • the activity of the candidate chimeric anti-LIGHT antibody in blocking the binding of LIGHT to its receptor HVEM was detected by ELISA.
  • the specific method was carried out according to the above-mentioned "ELISA method for detecting the activity of anti-LIGHT antibodies blocking the binding of LIGHT to LT ⁇ R", wherein the coating protein was HVEM-His (from Shutaishen).
  • the results are shown in Table 7.
  • the exemplary chimeric anti-LIGHT antibodies LT-m17, LT-m18, LT-m31, LT-m33, and LT-m37 can effectively block the binding of LIGHT to its receptor HVEM, and their neutralizing activities are better than those of the positive control antibody F19.
  • the cross-binding activity of the candidate chimeric anti-LIGHT antibody with cynomolgus monkey LIGHT and mouse LIGHT was detected by ELISA, and the specific method was carried out according to the above-mentioned "ELISA method for detecting the binding activity of anti-LIGHT antibodies" protocol, wherein the coated antigen was purified His-cynoLIGHT or His-musLIGHT protein.
  • the candidate chimeric anti-LIGHT antibodies LT-m17, LT-m18, LT-m31, LT-m33, and LT-m37 had weak cross-binding activity with mouse LIGHT, while the other chimeric antibodies had no cross-binding activity with mouse LIGHT (data not shown).
  • Biacore 8K was used to characterize the binding affinity of anti-LIGHT antibodies to human LIGHT and cynomolgus monkey LIGHT.
  • the anti-LIGHT antibodies were immobilized on the sensor chip CM5, and the affinity of antibodies of different concentrations to different species of LIGHT was detected.
  • the binding rate and dissociation rate of the antibodies were measured using SPR technology, and the binding affinity was determined.
  • the Kon, Koff and Kd values of the anti-LIGHT antibodies are shown in Table 8, from which it can be seen that the exemplary chimeric anti-LIGHT antibodies LT-m31, LT-m33, LT-m55, LT-m58, LT-m64, and LT-m85 bind to the human LIGHT antigen with high affinity.
  • Exemplary chimeric anti-LIGHT antibodies LT-m17, LT-m18, LT-m55, LT-m58, LT-m64, and LT-m85 also have strong cross-binding activity with cynomolgus monkey LIGHT.
  • Anti-LIGHT antibody inhibits the activity detection of human LIGHT activating LT ⁇ R reporter gene /
  • LIGHT After LIGHT binds to the LT ⁇ R receptor, it can activate the NF- ⁇ B pathway.
  • the constructed LT ⁇ R receptor stimuli-responsive luciferase reporter gene cell line (Hela-Rc32-NF- ⁇ B-Luc) was used to detect the ability of chimeric anti-LIGHT antibodies to inhibit the activation of LT ⁇ R receptors by LIGHT (including free LIGHT and cell surface LIGHT) and initiate luciferase signals, as a measure of the inhibitory effect of candidate chimeric anti-LIGHT antibodies on the LIGHT-activated LT ⁇ R-mediated signaling pathway.
  • a luciferase reporter gene cell line (Hela-Rc32-NF- ⁇ B-Luc) that responds to LT ⁇ R receptor stimuli was constructed.
  • the cervical cancer cell line Hela-Rc32 expresses the LT ⁇ R receptor, and because LIGHT activates the NF- ⁇ B pathway after binding to LT ⁇ R, the plasmid pGL4.32[luc2P/NF- ⁇ B-RE/Hygro] (Promega, Cat#E849A) was transfected into the Hela-Rc32 cell line.
  • the luciferase gene of the plasmid is located downstream of the NF- ⁇ B response element, and when LIGHT binds to LT ⁇ R, it can activate luciferase.
  • the construction method is as follows: According to the manufacturer's operating instructions, use The plasmid vector pGL4.32[luc2P/NF- ⁇ B-RE/Hygro] (Promega, Cat#E849A) was transfected into Hela-Rc32 cells (ATCC, CRL-2972) using 3000 reagent (Invitrogen, Cat#L3000-001) and cultured in complete medium containing antibiotics (DMEM, 10% FBS, 400 ⁇ g/ml Hygromycin B, 1% Penicillin-Streptomycin, abbreviated as PS) for monoclonal cell screening.
  • DMEM 10% FBS
  • Hygromycin B 400 ⁇ g/ml Hygromycin B
  • PS Penicillin-Streptomycin
  • monoclonal cells were selected and inoculated into a white transparent bottom 96-well plate at 1 ⁇ 10 4 cells/well, 50ng purified His-huLIGHT protein and 200 ⁇ l complete medium were added, and incubated at 37°C, 5% CO 2 for 24 hours. Then, 100 ⁇ l of luciferase substrate was added to each well, and the fluorescence (RLU) was detected after incubation in the dark for 5 minutes. Monoclonal cells with RLU values > 1000 or RLU net increase rate (LIGHT stimulation: control) ⁇ 4 were selected for expansion and further screening. After 3 rounds of repeated screening, the Hela-Rc32-NF- ⁇ B-Luc luciferase reporter gene cell line was obtained.
  • the LT ⁇ R receptor agonist-responsive luciferase reporter cell line Hela-Rc32-NF- ⁇ B-Luc was seeded into a white transparent bottom 96-well plate at a density of 1 ⁇ 10 4 cells/well and incubated in 200 ⁇ l complete culture medium (DMEM, 10% FBS, 400 ⁇ g/ml Hygromycin B, 1% PS), 37°C, 5% CO 2, and cultured overnight.
  • HEK293-LIGHT a stable cell line expressing LIGHT (HEK293-LIGHT) was constructed.
  • the construction method was as follows: according to the manufacturer's instructions, 2000 reagent (Invitrogen, catalog number 11668-027), the plasmid expressing LIGHT (from Shutaishen) was transfected into HEK293 cells, and cultured in complete medium containing antibiotics (DMEM, 10% FBS, 300 ⁇ g/ml Zeocin, 1% PS) for monoclonal screening and expansion of culture.
  • DMEM 10% FBS
  • Zeocin 300 ⁇ g/ml Zeocin, 1% PS
  • the selected LIGHT-positive cell lines were then identified by ELISA. Briefly, 4 ⁇ 10 4 cells/well of the above-mentioned LIGHT-positive cells were inoculated into a 96-well plate and cultured overnight at 37°C and 5% CO 2. After washing with 0.1% PBST buffer, 100 ⁇ L of 1% BSA solution was added to each well, and the plates were blocked at 37°C for 30 minutes. Subsequently, gradient concentrations of anti-LIGHT antibody F23-IgG4 (Cerecor) were added and incubated at 37°C for 1 hour. After washing, anti-human Fc-AP secondary antibody and colorimetric agent PNPP were added, and the OD405nm value was read with an enzyme reader to finally obtain the HEK293-LIGHT stably transfected cell line.
  • the luciferase reporter gene cell line Hela-Rc32-NF- ⁇ B-Luc which responds to LT ⁇ R receptor stimuli, was inoculated into a white transparent bottom 96-well plate at a density of 1 ⁇ 10 4 cells/well and cultured overnight at 37°C and 5% CO 2.
  • 50 ⁇ l/well of the HEK293-LIGHT stable cell suspension at a density of 2 ⁇ 10 5 cells/ml and 50 ⁇ l/well of the gradient dilution of the chimeric anti-LIGHT antibody to be tested (the starting concentration was 1600 ⁇ g/ml, and the gradient dilution was 1:3) were added, and the F19 antibody was used as a positive control.
  • the cells were cultured at 37°C and 5% CO 2 for 6 hours. Then, the fluorescence reading (Luminescence 1000ms) was detected using the ONE-Glo TM Luciferase Assay System detection method, and the specific method was as described above.
  • the results are shown in Figure 4.
  • the exemplary chimeric anti-LIGHT antibodies LT-m17, LT-m31, LT-m33, LT-m37 ( Figure 4A), LT-m55, LT-m58, LT-m64 ( Figure 4B), and LT-m85 ( Figure 4C) can effectively inhibit the activation of LT ⁇ R on the cell surface by LIGHT to initiate luciferase signal, and the inhibitory activity is better than that of the positive control antibody F19.
  • Anti-LIGHT antibody inhibits the activity detection of human LIGHT activating HVEM reporter gene /
  • LIGHT In addition to LT ⁇ R, LIGHT also binds to the HVEM receptor. After LIGHT binds to HVEM, it can also activate the NF- ⁇ B signaling pathway.
  • LIGHT By constructing a luciferase reporter gene cell line (293T-HVEM-NF- ⁇ B-Luc) that responds to HVEM receptor stimuli, LIGHT can activate luciferase after binding to HVEM, and detect the inhibitory effect of anti-LIGHT antibodies on the luciferase signal initiated by free LIGHT-activated HVEM receptors, as a measure of the activity of candidate chimeric antibodies to inhibit LIGHT-activated HVEM-mediated signaling pathways.
  • a luciferase reporter gene cell line (293T-HVEM-NF- ⁇ B-Luc) responsive to HVEM receptor agonism was constructed.
  • a lentiviral packaging system was used to construct the nucleic acid sequence encoding the HVEM-GFP-Blasticidin fusion protein into a lentiviral vector shuttle plasmid (from Shutaishen) to package a recombinant lentivirus.
  • 293T cells were inoculated into a 24-well plate at 5 ⁇ 10 4 cells/well.
  • the above-mentioned recombinant lentivirus was added according to different infection ratios (1, 2.5, 5 MOI), and DMEM medium containing 20% FBS was added to 1.2 ml, and cultured at 37°C and 5% CO 2 for 72 hours. Then, the culture medium containing 10 ⁇ g/ml Blasticidin was replaced for culture and screening. After 10 to 14 days, cells with positive GFP fluorescence signals (strong signals in the top 20%) were collected by flow cytometry.
  • the luciferase-expressing plasmid pGL4.32[luc2P/NF- ⁇ B-RE/Hygro] was transfected into the above-mentioned GFP-positive cells, and then the GFP-positive cells were sorted and collected by flow cytometry. After that, single clones were screened in a complete culture medium containing antibiotics (DMEM, 300 ⁇ g/ml Hygromycin B, 10 ⁇ g/ml Blasticidin, 1% PS), and after expanded culture, the luciferase reporter gene cell line 293T-HVEM-NF- ⁇ B-Luc that responded to HVEM receptor stimuli was obtained.
  • DMEM 300 ⁇ g/ml Hygromycin B, 10 ⁇ g/ml Blasticidin, 1% PS
  • the luciferase reporter gene cell line 293T-HVEM-NF- ⁇ B-Luc which responds to HVEM receptor stimuli, was inoculated into a white transparent bottom 96-well plate at a density of 1 ⁇ 10 4 cells/well and cultured overnight at 37°C and 5% CO 2 in 200 ⁇ l complete medium (DMEM, 10% FBS, 300 ⁇ g/ml Hygromycin B, 10 ⁇ g/ml Blasticidin, 1% PS).
  • the results are shown in Figure 5 and Table 9.
  • the exemplary chimeric anti-LIGHT antibodies LT-m17, LT-m31, LT-m33, LT-m37 ( Figure 5A and Table 9), LT-m55, LT-m64, LT-m85 ( Figure 5B and Table 9), and LT-m58 ( Figure 5C) can effectively inhibit the luciferase signal initiated by free LIGHT-activated HVEM, and the inhibitory activity is comparable to that of the positive control antibody F19.
  • variable region sequences of the heavy and light chains were compared with the sequences in the antibody germline database to obtain human germline templates with high homology.
  • the CDR region of the mouse antibody was transplanted to the selected human germline template to produce a humanized variable region, and then recombined with the corresponding human IgG constant region (preferably IgG4 heavy chain and ⁇ light chain).
  • the embedded residues, the residues that directly interact with the CDR region, and the residues that have an important influence on the conformation of VL and VH were back mutated, and the chemically unstable amino acid residues in the CDR region were optimized, thereby obtaining the final humanized molecules hum_LT-m37-1 to hum_LT-m37-16.
  • the variable domain sequences of the heavy chain and light chain of the humanized antibody are shown in Tables 2 and 3.
  • the chimeric antibody LT-m58 was also humanized, and the risk points in the CDR region were further optimized to obtain the corresponding humanized molecules hum_LT-m58-1 to hum_LT-m58-6.
  • the variable domain sequences of the heavy and light chains of the above humanized antibodies are shown in Table 2A and Table 3A.
  • the chimeric antibody LT-m85 was also humanized to obtain the corresponding humanized molecules hum_LT-m85-1 to hum_LT-m85-9.
  • the variable domain sequences of the heavy and light chains of the above humanized antibodies are shown in Table 2B and Table 3B.
  • Example 2 The corresponding experimental schemes in Example 2 were used to detect the affinity and biological activity of the humanized anti-LIGHT antibody, including affinity detection, neutralization activity detection and biological activity detection.
  • the "ELISA method for detecting the binding activity of anti-LIGHT antibodies” protocol described in Example 2 was used to detect the binding ability of the humanized antibody (human IgG4 form) to human LIGHT.
  • the results of the binding activity of the humanized molecules derived from the chimeric antibody LT-m37 are shown in FIG6 and Tables 10A-10B.
  • the humanized anti-LIGHT antibodies can effectively bind to the human LIGHT antigen, and their binding activity is better than or equivalent to that of the positive control antibody F19.
  • Table 10A Binding activity of humanized anti-LIGHT antibodies to human LIGHT
  • the results of the binding activity of the humanized molecules derived from the chimeric antibody LT-m58 are shown in Table 10C.
  • the humanized anti-LIGHT antibodies hum_LT-m58-1 to hum_LT-m58-6 can effectively bind to the human LIGHT antigen, and their binding activity is better than or equivalent to that of the positive control antibody F19.
  • Table 10C Binding activity of humanized anti-LIGHT antibody of LT-m58 to human LIGHT
  • the results of the binding activity of the humanized molecules derived from the chimeric antibody LT-m85 are shown in Table 10D.
  • the humanized anti-LIGHT antibodies hum_LT-m85-1 to hum_LT-m85-9 can all effectively bind to the human LIGHT antigen, and their binding activity is better than that of the positive control antibody F19.
  • Table 10D Binding activity of humanized anti-LIGHT antibody of LT-m85 to human LIGHT
  • the "ELISA method for detecting the activity of anti-LIGHT antibodies in blocking the binding of LIGHT to LT ⁇ R" described in Example 2 was used to detect the activity of humanized anti-LIGHT antibodies (human IgG4 form) in blocking the binding of LIGHT to LT ⁇ R, so as to measure the inhibitory ability of humanized anti-LIGHT antibodies on the pro-inflammatory mechanism mediated by LIGHT.
  • the results are shown in FIG. 7 and Tables 11A-11B .
  • the humanized anti-LIGHT antibodies derived from the chimeric antibody LT-m37 can effectively block the binding of human LIGHT to LT ⁇ R, and their blocking activity is better than that of the positive control antibody F19.
  • the exemplary humanized anti-LIGHT antibodies hum_LT-m37-13, hum_LT-m37-14, hum_LT-m37-15, hum_LT-m37-16 ( FIG. 7C and Table 11B ) showed comparable blocking activity on the binding of human LIGHT to LT ⁇ R.
  • Table 11A Humanized anti-LIGHT antibodies inhibit human LIGHT binding to human LT ⁇ R activity
  • Table 11B Humanized anti-LIGHT antibodies inhibit human LIGHT binding to human LT ⁇ R activity
  • the results of the neutralization activity of the humanized molecules derived from the chimeric antibody LT-m58 are shown in Table 11C.
  • the humanized anti-LIGHT antibodies hum_LT-m58-1 to hum_LT-m58-6 can effectively block the binding of human LIGHT to LT ⁇ R, and their blocking activity is better than that of the positive control antibody F19.
  • Table 11C Humanized anti-LIGHT antibody of LT-m58 inhibits human LIGHT binding to human LT ⁇ R activity
  • Hum_LT-m85-1 to hum_LT-m85-9 can effectively block the binding of human LIGHT to LT ⁇ R, and their blocking activity is better than that of the positive control antibody F19.
  • Table 11D Humanized anti-LIGHT antibody of LT-m85 inhibits human LIGHT binding to human LT ⁇ R activity
  • the ELISA method described in Example 2 was used to detect the species cross-binding activity of the humanized antibody (human IgG4 form) with cynomolgus monkey LIGHT and mouse LIGHT.
  • the results are shown in Table 12A.
  • the humanized anti-LIGHT antibody derived from the chimeric antibody LT-m37 has strong cross-binding activity with cynomolgus monkey LIGHT.
  • the humanized anti-LIGHT antibody had weak or no cross-binding activity with mouse LIGHT (data not shown).
  • Table 12B Cross-binding ability of LT-m58 humanized anti-LIGHT antibody with cynomolgus monkey LIGHT
  • hum_LT-m85-1 The results of species cross-binding activity of humanized molecules derived from chimeric antibody LT-m85 are shown in Table 12C.
  • Table 12C Cross-binding ability of LT-m85 humanized anti-LIGHT antibody with cynomolgus monkey LIGHT
  • Biacore 8K was used to characterize the binding affinity of humanized anti-LIGHT antibody to human LIGHT.
  • the anti-LIGHT antibody was immobilized on the sensor chip CM5, and the affinity of different concentrations of the humanized anti-LIGHT antibody (IgG4 form) to human LIGHT was detected.
  • the binding rate and dissociation rate of the antibody were measured using SPR technology, and the binding affinity was determined.
  • the Kon, Koff and Kd values of the anti-LIGHT antibodies are shown in Table 13, from which it can be seen that the exemplary humanized anti-LIGHT antibodies hum_LT-m37-4, hum_LT-m37-5, hum_LT-m37-6, hum_LT-m37-7, hum_LT-m37-8, hum_LT-m37-9, hum_LT-m37-11, and hum_LT-m37-12 bind to human LIGHT antigen with high affinity.
  • Humanized anti-LIGHT antibody inhibits free LIGHT from activating the LT ⁇ R reporter gene activity detection /
  • Example 2 The experiment of "Detection of the Activity of Anti-LIGHT Antibodies Inhibiting Human LIGHT from Activating LT ⁇ R Reporter Gene" described in Example 2 was used The scheme was to detect the inhibitory activity of humanized anti-LIGHT antibody on the free LIGHT-activated LT ⁇ R-mediated signaling pathway.
  • the results are shown in Figure 8 and Tables 14A-14B.
  • the humanized anti-LIGHT antibodies (human IgG4 format) derived from the chimeric antibody LT-m37 can effectively inhibit the activation of LT ⁇ R by free LIGHT to initiate luciferase signal, and the inhibitory activity is comparable to that of the positive control antibody F19.
  • the exemplary humanized anti-LIGHT antibodies hum_LT-m37-13, hum_LT-m37-14, hum_LT-m37-15, hum_LT-m37-16 ( FIG. 8C and Table 14B ) showed comparable inhibitory activity against free LIGHT-activated LT ⁇ R to initiate luciferase signaling.
  • Table 14A Humanized anti-LIGHT antibodies inhibit the activity of free LIGHT in activating the LT ⁇ R reporter gene
  • Table 14B Humanized anti-LIGHT antibodies inhibit the activity of free LIGHT in activating the LT ⁇ R reporter gene
  • the results of LT ⁇ R inhibitory activity of humanized molecules derived from chimeric antibody LT-m58 are shown in Table 14C.
  • the exemplary anti-LIGHT antibodies hum_LT-m58-1 and hum_LT-m58-2 can effectively inhibit the activation of LT ⁇ R by free LIGHT to initiate luciferase signal, and the inhibitory activity is better than that of the positive control antibody F19.
  • Table 14C Humanized anti-LIGHT antibody of LT-m58 inhibits the activity of free LIGHT in activating the LT ⁇ R reporter gene
  • the results of the LT ⁇ R inhibitory activity of the humanized molecules derived from the chimeric antibody LT-m85 are shown in Table 14D.
  • the exemplary anti-LIGHT antibodies hum_LT-m85-1, hum_LT-m85-2, hum_LT-m85-3, and hum_LT-m85-4 can effectively inhibit the activation of LT ⁇ R by free LIGHT to initiate luciferase signal, and the inhibitory activity is better than that of the positive control antibody F19.
  • Table 14D Humanized anti-LIGHT antibody of LT-m85 inhibits the activity of free LIGHT in activating the LT ⁇ R reporter gene
  • Humanized anti-LIGHT antibody inhibits the activity detection of cell surface LIGHT activating LT ⁇ R reporter gene /
  • Example 2 The experimental scheme of “Detection of the activity of anti-LIGHT antibody inhibiting human LIGHT activation of LT ⁇ R reporter gene” described in Example 2 was used to detect the inhibitory activity of humanized anti-LIGHT antibody on the cell surface LIGHT activation LT ⁇ R-mediated signaling pathway.
  • the results are shown in Figure 9 and Tables 15A-15B.
  • the humanized anti-LIGHT antibodies (human IgG4 format) derived from the chimeric antibody LT-m37 can effectively inhibit the activation of LT ⁇ R by cell surface LIGHT to initiate luciferase signal, and the inhibitory activity is better than that of the positive control antibody F19.
  • the exemplary humanized anti-LIGHT antibodies (human IgG4 format) hum_LT-m37-13, hum_LT-m37-14, hum_LT-m37-15, hum_LT-m37-16 ( FIG. 9C and Table 15B ) exhibited comparable inhibitory activity on the cell surface LIGHT-activated LT ⁇ R-induced luciferase signal.
  • Table 15A Humanized anti-LIGHT antibodies inhibit the activity of cell surface LIGHT to activate LT ⁇ R reporter gene
  • Table 15B Humanized anti-LIGHT antibodies inhibit the activity of cell surface LIGHT to activate LT ⁇ R reporter gene
  • the results of LT ⁇ R inhibitory activity of humanized molecules derived from chimeric antibody LT-m58 are shown in Table 15C.
  • the exemplary anti-LIGHT antibodies hum_LT-m58-1 and hum_LT-m58-2 can effectively inhibit the activation of LT ⁇ R by cell surface LIGHT to initiate luciferase signal, and the inhibitory activity is better than that of the positive control antibody F19.
  • Table 15C Humanized anti-LIGHT antibody of LT-m58 inhibits the activity of cell surface LIGHT in activating LT ⁇ R reporter gene
  • the results of the LT ⁇ R inhibitory activity of the humanized molecules derived from the chimeric antibody LT-m85 are shown in Table 15D.
  • the exemplary anti-LIGHT antibodies hum_LT-m85-1, hum_LT-m85-2, hum_LT-m85-3, and hum_LT-m85-4 can effectively inhibit the activation of LT ⁇ R by cell surface LIGHT to initiate luciferase signal, and the inhibitory activity is better than that of the positive control antibody F19.
  • Table 15D Humanized anti-LIGHT antibody of LT-m85 inhibits the activity of cell surface LIGHT in activating LT ⁇ R reporter gene
  • Humanized anti-LIGHT antibody inhibits free LIGHT from activating the HVEM reporter gene activity detection /
  • exemplary humanized anti-LIGHT antibodies (human IgG4 form) hum_LT-m37-1, hum_LT-m37-2, hum_LT-m37-3, hum_LT-m37-4, hum_LT-m37-5, hum_LT-m37-6 ( Figure 10A and Table 16A), hum_LT-m37-14, hum_LT-m37-15, hum_LT-m37-16 ( Figure 10B and Table 16B) derived from the chimeric antibody LT-m37 can effectively inhibit the activation of HVEM by free LIGHT to initiate luciferase signal, and the inhibitory activity is comparable to that of the positive control antibody F19.
  • Table 16A Humanized anti-LIGHT antibodies inhibit the activity of free LIGHT in activating the HVEM reporter gene
  • Table 16B Humanized anti-LIGHT antibodies inhibit the activity of free LIGHT in activating the HVEM reporter gene
  • HVEM inhibitory activity of humanized molecules derived from chimeric antibody LT-m58 are shown in Table 16C.
  • the exemplary anti-LIGHT antibodies hum_LT-m58-1 and hum_LT-m58-2 can effectively inhibit the activation of HVEM by free LIGHT to initiate luciferase signal, and the inhibitory activity is better than that of the positive control antibody F19.
  • Table 16C Humanized anti-LIGHT antibody of LT-m58 inhibits the activity of free LIGHT in activating the HVEM reporter gene
  • HVEM inhibitory activity of the humanized molecule derived from the chimeric antibody LT-m85 are shown in Table 16D.
  • the exemplary anti-LIGHT antibodies hum_LT-m85-1, hum_LT-m85-2, hum_LT-m85-3, and hum_LT-m85-4 can effectively inhibit the activation of HVEM by free LIGHT to initiate luciferase signal, and the inhibitory activity is better than that of the positive control antibody F19.
  • Table 16D Humanized anti-LIGHT antibody of LT-m85 inhibits the activity of free LIGHT in activating the HVEM reporter gene
  • BEAS-2B bronchial epithelial cells express both LT ⁇ R and HVEM receptors.
  • LIGHT binds to the receptors LT ⁇ R or HVEM, it can induce the secretion of MMP-9 by bronchial epithelial cells, thereby causing lung tissue damage.
  • MMP-9 produced by BEAS-2B bronchial epithelial cells, the ability of anti-LIGHT antibodies to inhibit free LIGHT from activating HVEM or LT ⁇ R receptors can be detected, which serves as a measure of the mechanism by which the tested antibody inhibits LIGHT activation to promote lung tissue remodeling.
  • BEAS-2B bronchial epithelial cells (ATCC, CRL-9609) were seeded into 96-well plates at a density of 2 ⁇ 10 4 cells/well and cultured overnight in 100 ⁇ l BMEM complete medium (Lonza, CC-3171, containing rhEGF, insulin, triiodothyronine-T3, BPE, transferrin, retinoic acid, epinephrine, hydrocortisone, GA-1000, supplemented with 1% PS) at 37°C and 5% CO 2.
  • BMEM complete medium Lionza, CC-3171, containing rhEGF, insulin, triiodothyronine-T3, BPE, transferrin, retinoic acid, epinephrine, hydrocortisone, GA-1000, supplemented with 1% PS
  • the epithelial cell culture medium was removed, and 50 ⁇ l of His-huLIGHT antigen at a concentration of 600 ng/ml and 50 ⁇ l of serial dilutions of The humanized anti-LIGHT antibody to be tested (starting at 300 ⁇ g/ml, then diluted 1:3), with F19 antibody as a positive control, was supplemented with 50 ⁇ l of culture medium/well, and cultured at 37°C and 5% CO 2 for 48 hours after slight shaking. The cell culture supernatant was collected and the level of human MMP-9 was detected using an ELISA kit (Boster, EK0465) according to the manufacturer's instructions.
  • OD 450nm was detected, and the MMP-9 level-antibody concentration curve was generated using GraphPad Prism 5.0 to calculate the IC 50 value of each antibody in inhibiting the production of MMP-9 by human LIGHT-induced BEAS-2B bronchial epithelial cells.
  • the inhibitory activity of exemplary humanized anti-LIGHT antibodies (human IgG4 form) hum_LT-m37-13, hum_LT-m37-14, hum_LT-m37-15, and hum_LT-m37-16 on LIGHT-induced BEAS-2B bronchial epithelial cell production of MMP-9 is better than or equivalent to that of the chimeric antibody LT-m37, and the inhibitory activity is equivalent to that of the positive control antibody F19.
  • CD3 + T cells require co-stimulatory signals.
  • CD3 molecules on the surface of CD3 + T cells are stimulated by agonists; on the other hand, CD3 + T cells express HVEM. After LIGHT binds to HVEM, co-stimulatory signals are released, thereby jointly inducing the activation and proliferation of T cells.
  • the inhibitory activity of humanized anti-LIGHT antibodies on LIGHT-induced T cell activation and proliferation is detected as a measure of the inhibitory effect of the humanized antibodies to be tested on the inflammatory mechanism mediated by LIGHT-activated T cells.
  • the anti-human CD3 agonist antibody (Biolegend, catalog number 317326) with a concentration of 2 ⁇ g/ml was coated on 100 ⁇ l/well of a 96-well plate and incubated at 4°C overnight. After washing the plate twice with DPBS buffer, 100 ⁇ l of His-huLIGHT protein with a concentration of 30 ⁇ g/ml was added to each well and incubated at 37°C for 4 hours. After washing the plate, the liquid in the well was removed for later use.
  • CD3 + T cells (Miaoshun/TPCS, PB-N-1C) with a density of 1.5 ⁇ 10 6 cells/ml were inoculated into 100 ⁇ l/well of the above 96-well plate, and 50 ⁇ l/well of gradient dilutions of the humanized anti-LIGHT antibody to be tested (starting concentration of 36 ⁇ g/ml, and then 1:3 gradient dilutions) were added, of which F19 antibody was used as a positive control, and irrelevant antibody IgG (from Shutaishen) was used as a negative control (abbreviated as NC). After slight shaking and mixing, the cells were cultured at 37°C and 5% CO 2 for 4 days.
  • CD3 + T cells were detected using the CellTiter-Glo luminescent cell viability assay (Promega, G7573).
  • 50 ⁇ l/well of CellTiter-Glo reagent was added, shaken for 2 minutes in the dark, and allowed to stand for 10 minutes.
  • 70 ⁇ l/well of the reaction supernatant was transferred to a white transparent bottom 96-well plate.
  • Luminescence was detected for 1000ms, and GraphPad Prism 5.0 was used to generate the Luminescence-antibody concentration curve, and the IC 50 value of each antibody for inhibiting the proliferation of human LIGHT-stimulated CD3 + T cells was calculated.
  • the exemplary humanized anti-LIGHT antibodies (human IgG4 form) hum_LT-m37-13, hum_LT-m37-14, hum_LT-m37-15, and hum_LT-m37-16 can effectively inhibit the activation and proliferation of CD3 + T cells stimulated by LIGHT, and the inhibitory activity is comparable to that of the positive control antibody F19.
  • Example 5 In vivo activity verification of anti-LIGHT antibody in LPS-induced mouse ARDS model
  • LPS-induced mouse ARDS model Lipopolysaccharide (LPS)-induced lung inflammation and immune system activation in mice can lead to the expression of LIGHT on the surface of immune cells and increase the level of free LIGHT.
  • LPS Lipopolysaccharide
  • the binding of LIGHT to its receptor LT ⁇ R or HVEM stimulates the activation of inflammatory cells, which is an important reason for the aggravation of inflammation and the promotion of the process of acute respiratory distress syndrome (ARDS).
  • ARDS acute respiratory distress syndrome
  • LPS-induced mouse ARDS model modeling and administration 7-week-old C57 mice were intraperitoneally injected with the modeling agent LPS 0.8 mpk, with an injection volume of 10 ml/kg. 16 hours later, the modeling agent 5 mg/ml was administered through the airway, with an injection volume of 25 ⁇ l/mouse.
  • anti-LIGHT antibodies were injected into the tail vein of the experimental group mice at a dose of 15 mpk.
  • the negative control group was injected with the same dose of an irrelevant antibody (from Shutaishen) in the same manner, and the model control group was injected with an equal volume of PBS solution in the same manner.
  • the mice were killed 48 hours after administration, and the alveolar lavage fluid was obtained for white blood cell counts, including the levels of total white blood cells, intermediate cells, neutrophils, and lymphocytes.
  • exemplary anti-LIGHT antibodies hum_LT-m37-13, hum_LT-m37-14, hum_LT-m37-15, hum_LT-m37-16 (human IgG4 form), hum_LT-m58-1, hum_LT-m58-2, hum_LT-m58-5, hum_LT-m58-6, hum_LT-m85-1, hum_LT-m85-2, hum_LT-m85-3, hum_LT-m85-4 can also effectively inhibit the levels of total leukocytes, intermediate cells, neutrophils and lymphocytes in the bronchoalveolar lavage fluid of the LPS-induced mouse ARDS model (data not shown).

Abstract

涉及特异性地识别LIGHT的抗体或抗原结合片段，及其制备方法和用途。

Description

特异性识别LIGHT的抗体及其应用
相关申请的交叉参考
本申请要求专利申请号为202211184544.9，申请日为2022.09.27，发明名称为“特异性识别LIGHT的抗体及其应用”的中国专利申请，以及专利申请号为202310861858.6，申请日为2023.07.13，发明名称为“特异性识别LIGHT的抗体及其应用”的中国专利申请的优先权，且该申请的全部内容以引用方式并入本文中。
以xml文件提交序列表
电子序列表的内容通过整体引用并入本文中：(LIGHT_WIPO_seq.xml；大小:92KB；以及创建日期:2023.07.11)。
技术领域
本发明涉及特异性识别LIGHT的抗体，及其制备方法和用途，包括用其治疗LIGHT信号通路失调导致的疾病和/或病症，例如自身免疫性疾病和/或炎症疾病的方法
背景技术
LIGHT(T淋巴细胞上可诱导表达的淋巴毒素样的与单疱疹病毒糖蛋白D竞争结合HVEM的受体)，作为肿瘤坏死因子超家族(TNFSF)的成员之一，也被称为肿瘤坏死因子超家族成员14(TNFSF14)或CD258，是一个包含240个氨基酸的II型跨膜蛋白，能够在细胞表面形成同源三聚体。LIGHT的三聚体结构使其能够聚集与之相互作用的细胞表面受体，从而启动共刺激信号通路的激活(Bobmer等人，2002，Trends Biochem.Sci.27,19–26)。LIGHT mRNA的可变剪接产生两种异构体：细胞质LIGHT(也被称为游离LIGHT)和膜结合型LIGHT(也被称为细胞表面LIGHT)(Morel等人，2000，J.Immunol.165，4397–4404)。
LIGHT在原初T细胞上不表达，但在活化的T细胞中表达上调。LIGHT在激活后以严格调控的方式在T细胞表面表达，其在4小时内出现，在12-24小时达到峰值，并在48小时消失(Castellano等人，2002，J Biol Chem 277 42841-51)。CD8+T细胞的激活上调LIGHT的表达量多于CD4+T细胞。LIGHT还以可检测的水平组成型地表达于未成熟的树突细胞(DC)表面(Tamada等人，2000，J Immunol 164 4105-10)。LIGHT也在自然杀伤(NK)细胞和单核细胞中表达(Cohavy等人，2005，J Immunol 174 646-53)。
LIGHT结合三种不同的受体：淋巴毒素β受体(LTβR)(Crowe等人，1994，Science 264707-10，Browning等人，1997，J Immunol 159 3288-98)、单纯疱疹病毒进入介导子(HVEM)(Montgomery等人，1996，Cell 87(3)427-36)以及诱骗受体3(DcR3)(Yu等人，1999，J Biol Chem 274 13733-6)。LIGHT序列中第119和174位的氨基酸突变能够破坏其与HVEM和LTβR受体的结合能力(Rooney等人，2000，J.Biol.Chem.275,14307–14315)。LTβR和HVEM的信号 传导途径均涉及TNFR相关因子(TRAF)的招募以及随后caspase和转录因子的激活。尽管这两个LIGHT受体之间有相似性，但由于其不同的表达模式以及结合不同信号分子，LTβR和HVEM所触发的下游信号事件是不同的(Zhai等人，1998，J Clin Invest；102(6):1142–1151)。
LTβR存在于上皮细胞、基质细胞、未成熟的DC和骨髓细胞的表面，但是在淋巴细胞中不表达(Giles等人，2018，Front Immunol.9:2585)。LTβR信号诱导参与促炎症反应的基因，包括MIP-1/2、粘附分子和趋化因子的激活(Dejardin E等人，2002，Immunity.17(4):525)。此外有研究报道LIGHT-LTβR信号控制脂质平衡并在血脂异常过程中发挥了作用(Combes JL等人，2007，J Exp Med.204(8):1757–1764)。在正常的生物发育过程中，LIGHT-LTβR的相互作用被认为是淋巴结构发育和维护的一个组成部分(Lu等人，2014，Front Immunol.5:47)。Scheu等人的研究发现，小鼠中LIGHT和LTβ的缺失导致所有二级淋巴结构的破坏(Scheu等人，2002，J Exp Med 195:1613-1624)。
与LIGHT结合后，LTβR被证明与包括TRAF2、TRAF3和κB抑制剂(IκB)激酶复合物(IKK)在内的信号复合物相关联。此外，LIGHT-LTβR的相互作用以TRAF2依赖的方式介导c-Jun N端激酶(JNK)、激活蛋白-1(AP-1)和核因子-κB(NF-κB)的激活(Kim WJ等人，2005,Immunology.114(2):272–279.)。LIGHT-LTβR介导的细胞凋亡似乎依赖于TRAF3而不是TRAF2(Rooney IA等人，2000，J Biol Chem.275(19):14307–14315.)。LIGHT-LTβR信号的作用范围很广，一方面，LIGHT-LTβR的功能可以正向调控和支持抗肿瘤免疫反应，其影响包括提高癌细胞对免疫反应的敏感性，修复混乱的肿瘤血管，并支持效应细胞的细胞迁移和渗入肿瘤(Joseph G.等人，Frontiers in Immonology,2020)。另一方面，Conlon TM等人的研究证明了治疗性地抑制LTβR信号，能够使肺部结构从吸烟引起的肺气肿和气道纤维化中恢复。阻断LTβR信号的作用能够阻断iBALT的形成、肺泡上皮细胞的凋亡以及重新启动内源性Wnt/β-catenin驱动的肺泡再生(Conlon TM等人，2020，Nature.588(7836):151-156)。
单纯疱疹病毒进入介导子(HVEM)，也被称为肿瘤坏死因子受体超家族成员14(TNFRSF14)，最初被认为是1型单纯疱疹病毒侵入人类或小鼠细胞的中介物(Montgomery,Cell 87(3),"427-"436，1996)。HVEM在主要的人类组织中都有表达，其中在造血系统细胞中表达水平最高。HVEM是不溶性的跨膜蛋白，包括细胞内结构域、跨膜结构域以及细胞外结构域(简称胞外域)。HVEM的胞外域包括3个富含半胱氨酸结构域(CRD)，被称作CRD1、CRD2和CRD3。HVEM可以和多种不同的配体相互作用，这些配体通过结合HVEM的CRD结构域向下游传递激活或抑制信号。其中一些配体递送共刺激信号，例如LIGHT和LTα；其他配体递送共抑制信号，例如CD160、糖蛋白D(gD)和BTLA(Murphy等人，Annu Rev Immunol.28:389，2010)。HVEM的CRD2和CRD3结构域与LIGHT相互作用(Ware等人，2008，Immunol.Rev.223,186-201)；BTLA和CD160与HVEM的CRD1和CRD2结合，并与HSV gD结合竞争(Compaan等人，2005，J.Biol.Chem.280,39553–39561.)。有研究报道CRD1结构域的缺失会导致HVEM-Ig的共刺激信号的传 递，表明CRD1对于由重组HVEM-Ig融合蛋白诱导的抑制性信号传递是必不可少的(Adams等人，2002，Am.J.Transplant.2,12–18.)。
LIGHT与HVEM的相互作用负责LIGHT主要的免疫刺激特性(Steinberg等人，2011，Immunol Rev.244:169–87)。表达于淋巴细胞、NK细胞、平滑肌和上皮细胞上的HVEM作为一个重要的T细胞刺激剂，导致T细胞的活化、增殖和存活(Ware CF等人，2011，Curr Opin Immunol 23:627-31)。为了激活T效应细胞，HVEM对LIGHT的共刺激作用是必要的，这种共刺激作用是以不依赖CD28的T细胞对T细胞的方式。这种促进炎症的相互作用增加了Th1细胞因子IFNγ和GM-CSF的表达。LIGHT与HVEM的接触能够诱导TRAFs(包括TRAF2)的招募，以及NF-κB和JNK/AP-1转录因子的激活，这些有助于T细胞在体内的存活。此外，HVEM还可以通过LIGHT介导的核因子-κB(NF-κB)RelA/p50信号触发NK细胞产生IFNγ(Fan等人，2006，Blood 107:1342-51)。肿瘤感应NK细胞产生的LIGHT是NK-DC串联的重要组成部分，这种串联发生在新的抗肿瘤反应的启动阶段(Holmes等人，2014，Proc Natl Acad Sci USA.111:E5688–96)。因此，LIGHT-HVEM介导的T细胞共刺激和NK-DC串联在治疗背景下产生抗肿瘤免疫力方面发挥了重要作用。
专利申请WO2008027338A2公开了一种能够特异性结合hLIGHT多肽的抗体，以及治疗个体中hLIGHT介导的疾病的方法，包含向该个体中施用特异性结合hLIGHT多肽的抗体，例如完全人源化抗体。
综上，已有证据表明LIGHT通过结合HVEM或LTβR受体能激活T细胞或固有免疫细胞介导的炎症反应，引发如自身免疫性疾病和/或炎症疾病。因此，使用治疗性抗体拮抗LIGHT能抑制由该信号通路诱导的免疫反应，为上述相关疾病提供新的治疗方法。
本文提及的所有出版物、专利、专利申请和已公开的专利申请中披露的内容，以引用方式全部并入本文中。
申请概述
在一些实施例中，提供一种分离的抗LIGHT抗体，包含重链可变结构域(VH)，所述VH包含：重链互补决定区(HC-CDR)1，其包含GYFIN(SEQ ID NO:1)；HC-CDR2，其包含RIYPYNVX1TFYNQNFKG(SEQ ID NO:45)，其中X1为D或N；和HC-CDR3，其包含GTHYYGSSGAMDY(SEQ ID NO:16)；以及轻链可变结构域(VL)，所述VL包含：轻链互补决定区(LC-CDR)1，其包含KASQNVGTAVA(SEQ ID NO:23)；LC-CDR2，其包含SASNRYT(SEQ ID NO:30)；和LC-CDR3，其包含QQYSSYPYT(SEQ ID NO:37)。
在一些实施例中，提供一种分离的抗LIGHT抗体，其包含VH，所述VH包含：HC-CDR1，其包含SEQ ID NO:1所示的氨基酸序列或其变体，所述变体包含至多约3个氨基酸的取代；HC-CDR2，其包含SEQ ID NOs:8-9中任一所示的氨基酸序列或其变体，所述变体包含至多约3个氨基酸的取代；和HC-CDR3，其包含SEQ ID NO:16所示的氨基酸序列或其变体，所述变体包含至 多约3个氨基酸的取代；以及VL，所述VL包含：LC-CDR1，其包含SEQ ID NO:23所示的氨基酸序列或其变体，所述变体包含至多约3个氨基酸的取代；LC-CDR2，其包含SEQ ID NO:30所示的氨基酸序列或其变体，所述变体包含至多约3个氨基酸的取代；和LC-CDR3，其包含SEQ ID NO:37所示的氨基酸序列或其变体，所述变体包含至多约3个氨基酸的取代。
在一些实施例中，提供一种分离的抗LIGHT抗体，其包含：VH，所述VH包含如SEQ ID NOs:46-53中任一氨基酸序列所示的VH包含的HC-CDR1、HC-CDR2和HC-CDR3，以及VL，所述VL包含如SEQ ID NOs:62-65中任一氨基酸序列所示的VL包含的LC-CDR1、LC-CDR2和LC-CDR3。
在一些实施例中，提供一种分离的抗LIGHT抗体，其包含：(i)VH，其包含如氨基酸序列SEQ ID NO:46所示的VH包含的HC-CDR1、HC-CDR2和HC-CDR3；以及VL，其包含如氨基酸序列SEQ ID NO:62所示的VL包含的LC-CDR1、LC-CDR2和LC-CDR3；(ii)VH，其包含如氨基酸序列SEQ ID NO:47所示的VH包含的HC-CDR1、HC-CDR2和HC-CDR3；以及VL，其包含如氨基酸序列SEQ ID NO:63所示的VL包含的LC-CDR1、LC-CDR2和LC-CDR3；(iii)VH，其包含如氨基酸序列SEQ ID NO:48所示的VH包含的HC-CDR1、HC-CDR2和HC-CDR3；以及VL，其包含如氨基酸序列SEQ ID NO:63所示的VL包含的LC-CDR1、LC-CDR2和LC-CDR3；(iv)VH，其包含如氨基酸序列SEQ ID NO:49所示的VH包含的HC-CDR1、HC-CDR2和HC-CDR3；以及VL，其包含如氨基酸序列SEQ ID NO:63所示的VL包含的LC-CDR1、LC-CDR2和LC-CDR3；(v)VH，其包含如氨基酸序列SEQ ID NO:50所示的VH包含的HC-CDR1、HC-CDR2和HC-CDR3；以及VL，其包含如氨基酸序列SEQ ID NO:63所示的VL包含的LC-CDR1、LC-CDR2和LC-CDR3；(vi)VH，其包含如氨基酸序列SEQ ID NO:47所示的VH包含的HC-CDR1、HC-CDR2和HC-CDR3；以及VL，其包含如氨基酸序列SEQ ID NO:64所示的VL包含的LC-CDR1、LC-CDR2和LC-CDR3；(vii)VH，其包含如氨基酸序列SEQ ID NO:48所示的VH包含的HC-CDR1、HC-CDR2和HC-CDR3；以及VL，其包含如氨基酸序列SEQ ID NO:64所示的VL包含的LC-CDR1、LC-CDR2和LC-CDR3；(viii)VH，其包含如氨基酸序列SEQ ID NO:49所示的VH包含的HC-CDR1、HC-CDR2和HC-CDR3；以及VL，其包含如氨基酸序列SEQ ID NO:64所示的VL包含的LC-CDR1、LC-CDR2和LC-CDR3；(ix)VH，其包含如氨基酸序列SEQ ID NO:50所示的VH包含的HC-CDR1、HC-CDR2和HC-CDR3；以及VL，其包含如氨基酸序列SEQ ID NO:64所示的VL包含的LC-CDR1、LC-CDR2和LC-CDR3；(x)VH，其包含如氨基酸序列SEQ ID NO:47所示的VH包含的HC-CDR1、HC-CDR2和HC-CDR3；以及VL，其包含如氨基酸序列SEQ ID NO:65所示的VL包含的LC-CDR1、LC-CDR2和LC-CDR3；(xi)VH，其包含如氨基酸序列SEQ ID NO:48所示的VH包含的HC-CDR1、HC-CDR2和HC-CDR3；以及VL，其包含如氨基酸序列SEQ ID NO:65所示的VL包含的LC-CDR1、LC-CDR2和LC-CDR3；(xii)VH，其包含如氨基酸序列SEQ ID NO:49所示的VH包含的HC-CDR1、HC-CDR2和HC-CDR3；以及VL，其包含如氨基酸序列SEQ ID NO:65所示的VL包含的LC-CDR1、LC-CDR2和LC-CDR3；(xiii)VH，其包含如氨基酸序列 SEQ ID NO:50所示的VH包含的HC-CDR1、HC-CDR2和HC-CDR3；以及VL，其包含如氨基酸序列SEQ ID NO:65所示的VL包含的LC-CDR1、LC-CDR2和LC-CDR3；(xiv)VH，其包含如氨基酸序列SEQ ID NO:51所示的VH包含的HC-CDR1、HC-CDR2和HC-CDR3；以及VL，其包含如氨基酸序列SEQ ID NO:63所示的VL包含的LC-CDR1、LC-CDR2和LC-CDR3；(xv)VH，其包含如氨基酸序列SEQ ID NO:52所示的VH包含的HC-CDR1、HC-CDR2和HC-CDR3；以及VL，其包含如氨基酸序列SEQ ID NO:65所示的VL包含的LC-CDR1、LC-CDR2和LC-CDR3；(xvi)VH，其包含如氨基酸序列SEQ ID NO:53所示的VH包含的HC-CDR1、HC-CDR2和HC-CDR3；以及VL，其包含如氨基酸序列SEQ ID NO:65所示的VL包含的LC-CDR1、LC-CDR2和LC-CDR3；(xvii)VH，其包含如氨基酸序列SEQ ID NO:51所示的VH包含的HC-CDR1、HC-CDR2和HC-CDR3；以及VL，其包含如氨基酸序列SEQ ID NO:65所示的VL包含的LC-CDR1、LC-CDR2和LC-CDR3。
在一些实施例中，提供一种分离的抗LIGHT抗体，其包含：(i)VH，所述VH包含：HC-CDR1，其包含氨基酸序列SEQ ID NO:1，HC-CDR2，其包含氨基酸序列SEQ ID NO:8，和HC-CDR3，其包含氨基酸序列SEQ ID NO:16，或者所述VH的变体，其HC-CDRs中包含至多约5个氨基酸的取代；以及VL，所述VL包含：LC-CDR1，其包含氨基酸序列SEQ ID NO:23，LC-CDR2，其包含氨基酸序列SEQ ID NO:30，和LC-CDR3，其包含氨基酸序列SEQ ID NO:37，或者所述VL的变体，其LC-CDRs中包含至多约5个氨基酸的取代；(ii)VH，所述VH包含：HC-CDR1，其包含氨基酸序列SEQ ID NO:1，HC-CDR2，其包含氨基酸序列SEQ ID NO:9，和HC-CDR3，其包含氨基酸序列SEQ ID NO:16，或者所述VH的变体，其HC-CDRs中包含至多约5个氨基酸的取代；以及VL，所述VL包含：LC-CDR1，其包含氨基酸序列SEQ ID NO:23，LC-CDR2，其包含氨基酸序列SEQ ID NO:30，和LC-CDR3，其包含氨基酸序列SEQ ID NO:37，或者所述VL的变体，其LC-CDRs中包含至多约5个氨基酸的取代。
在一些实施例中，如上所述任一种分离的抗LIGHT抗体，其包含：VH，其包含SEQ ID NOs:46-53中任一所示的氨基酸序列或其变体，所述变体与SEQ ID NOs:46-53中任一所示的氨基酸序列具有至少约80％序列同一性；以及VL，其包含SEQ ID NOs:62-65中任一所示的氨基酸序列或其变体，所述变体与SEQ ID NOs:62-65中任一所示的氨基酸序列具有至少约80％序列同一性。
在一些实施例中，提供一种分离的抗LIGHT抗体包含：(i)VH，其包含氨基酸序列SEQ ID NO:46或其变体，所述变体与氨基酸序列SEQ ID NO:46具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:62或其变体，所述变体与氨基酸序列SEQ ID NO:62具有至少约80％序列同一性；(ii)VH，其包含氨基酸序列SEQ ID NO:47或其变体，所述变体与氨基酸序列SEQ ID NO:47具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:63或其变体，所述变体与氨基酸序列SEQ ID NO:63具有至少约80％序列同一性；(iii)VH，其包含氨基酸序列SEQ ID NO:48或其变体，所述变体与氨基酸序列SEQ ID NO:48具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:63或其变体，所述变体与氨基酸序列SEQ ID NO:63具 有至少约80％序列同一性；(iv)VH，其包含氨基酸序列SEQ ID NO:49或其变体，所述变体与氨基酸序列SEQ ID NO:49具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:63或其变体，所述变体与氨基酸序列SEQ ID NO:63具有至少约80％序列同一性；(v)VH，其包含氨基酸序列SEQ ID NO:50或其变体，所述变体与氨基酸序列SEQ ID NO:50具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:63或其变体，所述变体与氨基酸序列SEQ ID NO:63具有至少约80％序列同一性；(vi)VH，其包含氨基酸序列SEQ ID NO:47或其变体，所述变体与氨基酸序列SEQ ID NO:47具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:64或其变体，所述变体与氨基酸序列SEQ ID NO:64具有至少约80％序列同一性；(vii)VH，其包含氨基酸序列SEQ ID NO:48或其变体，所述变体与氨基酸序列SEQ ID NO:48具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:64或其变体，所述变体与氨基酸序列SEQ ID NO:64具有至少约80％序列同一性；(viii)VH，其包含氨基酸序列SEQ ID NO:49或其变体，所述变体与氨基酸序列SEQ ID NO:49具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:64或其变体，所述变体与氨基酸序列SEQ ID NO:64具有至少约80％序列同一性；(ix)VH，其包含氨基酸序列SEQ ID NO:50或其变体，所述变体与氨基酸序列SEQ ID NO:50具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:64或其变体，所述变体与氨基酸序列SEQ ID NO:64具有至少约80％序列同一性；(x)VH，其包含氨基酸序列SEQ ID NO:47或其变体，所述变体与氨基酸序列SEQ ID NO:47具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:65或其变体，所述变体与氨基酸序列SEQ ID NO:65具有至少约80％序列同一性；(xi)VH，其包含氨基酸序列SEQ ID NO:48或其变体，所述变体与氨基酸序列SEQ ID NO:48具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:65或其变体，所述变体与氨基酸序列SEQ ID NO:65具有至少约80％序列同一性；(xii)VH，其包含氨基酸序列SEQ ID NO:49或其变体，所述变体与氨基酸序列SEQ ID NO:49具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:65或其变体，所述变体与氨基酸序列SEQ ID NO:65具有至少约80％序列同一性；(xiii)VH，其包含氨基酸序列SEQ ID NO:50或其变体，所述变体与氨基酸序列SEQ ID NO:50具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:65或其变体，所述变体与氨基酸序列SEQ ID NO:65具有至少约80％序列同一性；(xiv)VH，其包含氨基酸序列SEQ ID NO:51或其变体，所述变体与氨基酸序列SEQ ID NO:51具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:63或其变体，所述变体与氨基酸序列SEQ ID NO:63具有至少约80％序列同一性；(xv)VH，其包含氨基酸序列SEQ ID NO:52或其变体，所述变体与氨基酸序列SEQ ID NO:52具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:65或其变体，所述变体与氨基酸序列SEQ ID NO:65具有至少约80％序列同一性；(xvi)VH，其包含氨基酸序列SEQ ID NO:53或其变体，所述变体与氨基酸序列SEQ ID NO:53具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:65或其变体，所述变体与氨基酸序列SEQ ID NO:65具有至少约80％序列同一性；(xvii)VH，其包含氨基酸序列SEQ ID NO:51或其变体，所述 变体与氨基酸序列SEQ ID NO:51具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:65或其变体，所述变体与氨基酸序列SEQ ID NO:65具有至少约80％序列同一性。
在一些实施例中，提供一种分离的抗LIGHT抗体，其包含：(i)VH，其包含如氨基酸序列SEQ ID NO:54所示的VH包含的HC-CDR1、HC-CDR2和HC-CDR3；以及VL，其包含如氨基酸序列SEQ ID NO:66所示的VL包含的LC-CDR1、LC-CDR2和LC-CDR3。
在一些实施例中，提供一种分离的抗LIGHT抗体，其包含：(i)VH，所述VH包含：HC-CDR1，其包含氨基酸序列SEQ ID NO:2，HC-CDR2，其包含氨基酸序列SEQ ID NO:10，和HC-CDR3，其包含氨基酸序列SEQ ID NO:17，或者所述VH的变体，其HC-CDRs中包含至多约5个氨基酸的取代；以及VL，所述VL包含：LC-CDR1，其包含氨基酸序列SEQ ID NO:24，LC-CDR2，其包含氨基酸序列SEQ ID NO:31，和LC-CDR3，其包含氨基酸序列SEQ ID NO:38，或者所述VL的变体，其LC-CDRs中包含至多约5个氨基酸的取代。
在一些实施例中，如上所述任一种分离的抗LIGHT抗体，其包含：VH，其包含SEQ ID NO:54所示的氨基酸序列或其变体，所述变体与SEQ ID NO:54所示的氨基酸序列具有至少约80％序列同一性；以及VL，其包含SEQ ID NO:66所示的氨基酸序列或其变体，所述变体与SEQ ID NO:66所示的氨基酸序列具有至少约80％序列同一性。
在一些实施例中，提供一种分离的抗LIGHT抗体，其包含：(i)VH，其包含如氨基酸序列SEQ ID NO:55所示的VH包含的HC-CDR1、HC-CDR2和HC-CDR3；以及VL，其包含如氨基酸序列SEQ ID NO:67所示的VL包含的LC-CDR1、LC-CDR2和LC-CDR3。
在一些实施例中，提供一种分离的抗LIGHT抗体，其包含：(i)VH，所述VH包含：HC-CDR1，其包含氨基酸序列SEQ ID NO:2，HC-CDR2，其包含氨基酸序列SEQ ID NO:10，和HC-CDR3，其包含氨基酸序列SEQ ID NO:17，或者所述VH的变体，其HC-CDRs中包含至多约5个氨基酸的取代；以及VL，所述VL包含：LC-CDR1，其包含氨基酸序列SEQ ID NO:25，LC-CDR2，其包含氨基酸序列SEQ ID NO:31，和LC-CDR3，其包含氨基酸序列SEQ ID NO:39，或者所述VL的变体，其LC-CDRs中包含至多约5个氨基酸的取代。
在一些实施例中，如上所述任一种分离的抗LIGHT抗体，其包含：VH，其包含SEQ ID NO:55所示的氨基酸序列或其变体，所述变体与SEQ ID NO:55所示的氨基酸序列具有至少约80％序列同一性；以及VL，其包含SEQ ID NO:67所示的氨基酸序列或其变体，所述变体与SEQ ID NO:67所示的氨基酸序列具有至少约80％序列同一性。
在一些实施例中，提供一种分离的抗LIGHT抗体，其包含：(i)VH，其包含如氨基酸序列SEQ ID NO:56所示的VH包含的HC-CDR1、HC-CDR2和HC-CDR3；以及VL，其包含如氨基酸序列SEQ ID NO:68所示的VL包含的LC-CDR1、LC-CDR2和LC-CDR3。
在一些实施例中，提供一种分离的抗LIGHT抗体，其包含：(i)VH，所述VH包含：HC-CDR1，其包含氨基酸序列SEQ ID NO:3，HC-CDR2，其包含氨基酸序列SEQ ID NO:11，和HC-CDR3，其包含氨基酸序列SEQ ID NO:18，或者所述VH的变体，其HC-CDRs中包含至多约5个 氨基酸的取代；以及VL，所述VL包含：LC-CDR1，其包含氨基酸序列SEQ ID NO:26，LC-CDR2，其包含氨基酸序列SEQ ID NO:32，和LC-CDR3，其包含氨基酸序列SEQ ID NO:40，或者所述VL的变体，其LC-CDRs中包含至多约5个氨基酸的取代。
在一些实施例中，如上所述任一种分离的抗LIGHT抗体，其包含：VH，其包含SEQ ID NO:56所示的氨基酸序列或其变体，所述变体与SEQ ID NO:56所示的氨基酸序列具有至少约80％序列同一性；以及VL，其包含SEQ ID NO:68所示的氨基酸序列或其变体，所述变体与SEQ ID NO:68所示的氨基酸序列具有至少约80％序列同一性。
在一些实施例中，提供一种分离的抗LIGHT抗体，其包含：(i)VH，其包含如氨基酸序列SEQ ID NO:57所示的VH包含的HC-CDR1、HC-CDR2和HC-CDR3；以及VL，其包含如氨基酸序列SEQ ID NO:69所示的VL包含的LC-CDR1、LC-CDR2和LC-CDR3。
在一些实施例中，提供一种分离的抗LIGHT抗体，其包含：(i)VH，所述VH包含：HC-CDR1，其包含氨基酸序列SEQ ID NO:3，HC-CDR2，其包含氨基酸序列SEQ ID NO:11，和HC-CDR3，其包含氨基酸序列SEQ ID NO:18，或者所述VH的变体，其HC-CDRs中包含至多约5个氨基酸的取代；以及VL，所述VL包含：LC-CDR1，其包含氨基酸序列SEQ ID NO:26，LC-CDR2，其包含氨基酸序列SEQ ID NO:32，和LC-CDR3，其包含氨基酸序列SEQ ID NO:41，或者所述VL的变体，其LC-CDRs中包含至多约5个氨基酸的取代。
在一些实施例中，如上所述任一种分离的抗LIGHT抗体，其包含：VH，其包含SEQ ID NO:57所示的氨基酸序列或其变体，所述变体与SEQ ID NO:57所示的氨基酸序列具有至少约80％序列同一性；以及VL，其包含SEQ ID NO:69所示的氨基酸序列或其变体，所述变体与SEQ ID NO:69所示的氨基酸序列具有至少约80％序列同一性。
在一些实施例中，提供一种分离的抗LIGHT抗体，其包含：(i)VH，其包含如氨基酸序列SEQ ID NO:58所示的VH包含的HC-CDR1、HC-CDR2和HC-CDR3；以及VL，其包含如氨基酸序列SEQ ID NO:70所示的VL包含的LC-CDR1、LC-CDR2和LC-CDR3。
在一些实施例中，提供一种分离的抗LIGHT抗体，其包含：(i)VH，所述VH包含：HC-CDR1，其包含氨基酸序列SEQ ID NO:4，HC-CDR2，其包含氨基酸序列SEQ ID NO:12，和HC-CDR3，其包含氨基酸序列SEQ ID NO:19，或者所述VH的变体，其HC-CDRs中包含至多约5个氨基酸的取代；以及VL，所述VL包含：LC-CDR1，其包含氨基酸序列SEQ ID NO:27，LC-CDR2，其包含氨基酸序列SEQ ID NO:33，和LC-CDR3，其包含氨基酸序列SEQ ID NO:42，或者所述VL的变体，其LC-CDRs中包含至多约5个氨基酸的取代。
在一些实施例中，如上所述任一种分离的抗LIGHT抗体，其包含：VH，其包含SEQ ID NO:58所示的氨基酸序列或其变体，所述变体与SEQ ID NO:58所示的氨基酸序列具有至少约80％序列同一性；以及VL，其包含SEQ ID NO:70所示的氨基酸序列或其变体，所述变体与SEQ ID NO:70所示的氨基酸序列具有至少约80％序列同一性。
在一些实施例中，提供一种分离的抗LIGHT抗体，其包含：(i)VH，其包含如氨基酸序列SEQ ID NO:59所示的VH包含的HC-CDR1、HC-CDR2和HC-CDR3；以及VL，其包含如氨基酸序列SEQ ID NO:71所示的VL包含的LC-CDR1、LC-CDR2和LC-CDR3。
在一些实施例中，提供一种分离的抗LIGHT抗体，其包含：(i)VH，所述VH包含：HC-CDR1，其包含氨基酸序列SEQ ID NO:5，HC-CDR2，其包含氨基酸序列SEQ ID NO:13，和HC-CDR3，其包含氨基酸序列SEQ ID NO:20，或者所述VH的变体，其HC-CDRs中包含至多约5个氨基酸的取代；以及VL，所述VL包含：LC-CDR1，其包含氨基酸序列SEQ ID NO:28，LC-CDR2，其包含氨基酸序列SEQ ID NO:34，和LC-CDR3，其包含氨基酸序列SEQ ID NO:43，或者所述VL的变体，其LC-CDRs中包含至多约5个氨基酸的取代。
在一些实施例中，如上所述任一种分离的抗LIGHT抗体，其包含：VH，其包含SEQ ID NO:59所示的氨基酸序列或其变体，所述变体与SEQ ID NO:59所示的氨基酸序列具有至少约80％序列同一性；以及VL，其包含SEQ ID NO:71所示的氨基酸序列或其变体，所述变体与SEQ ID NO:71所示的氨基酸序列具有至少约80％序列同一性。
在一些实施例中，提供一种分离的抗LIGHT抗体，包含重链可变结构域(VH)，所述VH包含重链互补决定区(HC-CDR)1，其包含DHIMN(SEQ ID NO:6)；HC-CDR2，其包含RIYPVSGETNYNQKFMG(SEQ ID NO:14)；和HC-CDR3，其包含GSYYWNAMDY(SEQ ID NO:21)；以及轻链可变结构域(VL)，所述VL包含：轻链互补决定区(LC-CDR)1，其包含KASQSVDFDGDSYMN(SEQ ID NO:29)或KASQSVDFDGESYMN(SEQ ID NO:83)；LC-CDR2，其包含SASNLES(SEQ ID NO:35)；和LC-CDR3，其包含QQSIEDPWT(SEQ ID NO:43)。
在一些实施例中，提供一种分离的抗LIGHT抗体，其包含VH，所述VH包含：HC-CDR1，其包含SEQ ID NO:6所示的氨基酸序列或其变体，所述变体包含至多约3个氨基酸的取代；HC-CDR2，其包含SEQ ID NO:14所示的氨基酸序列或其变体，所述变体包含至多约3个氨基酸的取代；和HC-CDR3，其包含SEQ ID NO:21所示的氨基酸序列或其变体，所述变体包含至多约3个氨基酸的取代；以及VL，所述VL包含：LC-CDR1，其包含SEQ ID NOs:29或83中任一所示的氨基酸序列或其变体，所述变体包含至多约3个氨基酸的取代；LC-CDR2，其包含SEQ ID NO:35所示的氨基酸序列或其变体，所述变体包含至多约3个氨基酸的取代；和LC-CDR3，其包含SEQ ID NO:43所示的氨基酸序列或其变体，所述变体包含至多约3个氨基酸的取代。
在一些实施例中，提供一种分离的抗LIGHT抗体，其包含：VH，所述VH包含如SEQ ID NOs:60，84-85中任一氨基酸序列所示的VH包含的HC-CDR1、HC-CDR2和HC-CDR3，以及VL，所述VL包含如SEQ ID NOs:72，86-91中任一氨基酸序列所示的VL包含的LC-CDR1、LC-CDR2和LC-CDR3。
在一些实施例中，提供一种分离的抗LIGHT抗体，其包含：(i)VH，其包含如氨基酸序列SEQ ID NO:60所示的VH包含的HC-CDR1、HC-CDR2和HC-CDR3；以及VL，其包含如氨基酸 序列SEQ ID NO:72所示的VL包含的LC-CDR1、LC-CDR2和LC-CDR3；(ii)VH，其包含如氨基酸序列SEQ ID NO:84所示的VH包含的HC-CDR1、HC-CDR2和HC-CDR3；以及VL，其包含如氨基酸序列SEQ ID NO:86所示的VL包含的LC-CDR1、LC-CDR2和LC-CDR3；(iii)VH，其包含如氨基酸序列SEQ ID NO:85所示的VH包含的HC-CDR1、HC-CDR2和HC-CDR3；以及VL，其包含如氨基酸序列SEQ ID NO:87所示的VL包含的LC-CDR1、LC-CDR2和LC-CDR3；(iv)VH，其包含如氨基酸序列SEQ ID NO:84所示的VH包含的HC-CDR1、HC-CDR2和HC-CDR3；以及VL，其包含如氨基酸序列SEQ ID NO:88所示的VL包含的LC-CDR1、LC-CDR2和LC-CDR3；(v)VH，其包含如氨基酸序列SEQ ID NO:84所示的VH包含的HC-CDR1、HC-CDR2和HC-CDR3；以及VL，其包含如氨基酸序列SEQ ID NO:89所示的VL包含的LC-CDR1、LC-CDR2和LC-CDR3；(vi)VH，其包含如氨基酸序列SEQ ID NO:85所示的VH包含的HC-CDR1、HC-CDR2和HC-CDR3；以及VL，其包含如氨基酸序列SEQ ID NO:90所示的VL包含的LC-CDR1、LC-CDR2和LC-CDR3；(vii)VH，其包含如氨基酸序列SEQ ID NO:84所示的VH包含的HC-CDR1、HC-CDR2和HC-CDR3；以及VL，其包含如氨基酸序列SEQ ID NO:91所示的VL包含的LC-CDR1、LC-CDR2和LC-CDR3。
在一些实施例中，提供一种分离的抗LIGHT抗体，其包含：(i)VH，所述VH包含：HC-CDR1，其包含氨基酸序列SEQ ID NO:6，HC-CDR2，其包含氨基酸序列SEQ ID NO:14，和HC-CDR3，其包含氨基酸序列SEQ ID NO:21，或者所述VH的变体，其HC-CDRs中包含至多约5个氨基酸的取代；以及VL，所述VL包含：LC-CDR1，其包含氨基酸序列SEQ ID NO:29，LC-CDR2，其包含氨基酸序列SEQ ID NO:35，和LC-CDR3，其包含氨基酸序列SEQ ID NO:43，或者所述VL的变体，其LC-CDRs中包含至多约5个氨基酸的取代；(ii)VH，所述VH包含：HC-CDR1，其包含氨基酸序列SEQ ID NO:6，HC-CDR2，其包含氨基酸序列SEQ ID NO:14，和HC-CDR3，其包含氨基酸序列SEQ ID NO:21，或者所述VH的变体，其HC-CDRs中包含至多约5个氨基酸的取代；以及VL，所述VL包含：LC-CDR1，其包含氨基酸序列SEQ ID NO:83，LC-CDR2，其包含氨基酸序列SEQ ID NO:35，和LC-CDR3，其包含氨基酸序列SEQ ID NO:43，或者所述VL的变体，其LC-CDRs中包含至多约5个氨基酸的取代。
在一些实施例中，如上所述任一种分离的抗LIGHT抗体，其包含：VH，其包含SEQ ID NOs:60，84-85中任一所示的氨基酸序列或其变体，所述变体与SEQ ID NOs:60，84-85中任一所示的氨基酸序列具有至少约80％序列同一性；以及VL，其包含SEQ ID NOs:72，86-91中任一所示的氨基酸序列或其变体，所述变体与SEQ ID NOs:72，86-91中任一所示的氨基酸序列具有至少约80％序列同一性。
在一些实施例中，如上所述任一种分离的抗LIGHT抗体，其包含：(i)VH，其包含SEQ ID NO:60所示的氨基酸序列或其变体，所述变体与SEQ ID NO:60所示的氨基酸序列具有至少约80％序列同一性；以及VL，其包含SEQ ID NO:72所示的氨基酸序列或其变体，所述变体与SEQ ID NO:72所示的氨基酸序列具有至少约80％序列同一性；(ii)VH，其包含氨基酸序列SEQ ID NO: 84或其变体，所述变体与氨基酸序列SEQ ID NO:84具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:86或其变体，所述变体与氨基酸序列SEQ ID NO:86具有至少约80％序列同一性；(iii)VH，其包含氨基酸序列SEQ ID NO:85或其变体，所述变体与氨基酸序列SEQ ID NO:85具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:87或其变体，所述变体与氨基酸序列SEQ ID NO:87具有至少约80％序列同一性；(iv)VH，其包含氨基酸序列SEQ ID NO:84或其变体，所述变体与氨基酸序列SEQ ID NO:84具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:88或其变体，所述变体与氨基酸序列SEQ ID NO:88具有至少约80％序列同一性；(v)VH，其包含氨基酸序列SEQ ID NO:84或其变体，所述变体与氨基酸序列SEQ ID NO:84具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:89或其变体，所述变体与氨基酸序列SEQ ID NO:89具有至少约80％序列同一性；(vi)VH，其包含氨基酸序列SEQ ID NO:85或其变体，所述变体与氨基酸序列SEQ ID NO:85具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:90或其变体，所述变体与氨基酸序列SEQ ID NO:90具有至少约80％序列同一性；或(vii)VH，其包含氨基酸序列SEQ ID NO:84或其变体，所述变体与氨基酸序列SEQ ID NO:84具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:91或其变体，所述变体与氨基酸序列SEQ ID NO:91具有至少约80％序列同一性。
在一些实施例中，提供一种分离的抗LIGHT抗体，包含重链可变结构域(VH)，所述VH包含：重链互补决定区(HC-CDR)1，其包含SYNVH(SEQ ID NO:7)；HC-CDR2，其包含AVYPGNGDTSYNQKFKG(SEQ ID NO:15)；和HC-CDR3，其包含GSYYYTSSYFDH(SEQ ID NO:22)；以及轻链可变结构域(VL)，所述VL包含：轻链互补决定区(LC-CDR)1，其包含KASQSVDFDGDSYMN(SEQ ID NO:29)；LC-CDR2，其包含TASNLES(SEQ ID NO:36)；和LC-CDR3，其包含QQSYEDPFT(SEQ ID NO:44)。
在一些实施例中，提供一种分离的抗LIGHT抗体，其包含：VH，所述VH包含如SEQ ID NOs:61，92-94中任一氨基酸序列所示的VH包含的HC-CDR1、HC-CDR2和HC-CDR3；以及VL，所述VL包含如SEQ ID NOs:73，95-99中任一氨基酸序列所示的VL包含的LC-CDR1、LC-CDR2和LC-CDR3。
在一些实施例中，提供一种分离的抗LIGHT抗体，其包含：(i)VH，其包含如氨基酸序列SEQ ID NO:61所示的VH包含的HC-CDR1、HC-CDR2和HC-CDR3；以及VL，其包含如氨基酸序列SEQ ID NO:73所示的VL包含的LC-CDR1、LC-CDR2和LC-CDR3。
在一些实施例中，提供一种分离的抗LIGHT抗体，其包含：(i)VH，所述VH包含：HC-CDR1，其包含氨基酸序列SEQ ID NO:7，HC-CDR2，其包含氨基酸序列SEQ ID NO:15，和HC-CDR3，其包含氨基酸序列SEQ ID NO:22，或者所述VH的变体，其HC-CDRs中包含至多约5个氨基酸的取代；以及VL，所述VL包含：LC-CDR1，其包含氨基酸序列SEQ ID NO:29，LC-CDR2，其包含氨基酸序列SEQ ID NO:36，和LC-CDR3，其包含氨基酸序列SEQ ID NO:44，或者所述VL的变体，其LC-CDRs中包含至多约5个氨基酸的取代。
在一些实施例中，如上所述任一种分离的抗LIGHT抗体，其包含：VH，其包含SEQ ID NOs:61，92-94中任一所示的氨基酸序列或其变体，所述变体与SEQ ID NOs:61，92-94中任一所示的氨基酸序列具有至少约80％序列同一性；以及VL，其包含SEQ ID NOs:73，95-99中任一所示的氨基酸序列或其变体，所述变体与SEQ ID NOs:73，95-99中任一所示的氨基酸序列具有至少约80％序列同一性。
在一些实施例中，如上所述任一种分离的抗LIGHT抗体，其包含：(i)VH，其包含SEQ ID NO:61所示的氨基酸序列或其变体，所述变体与SEQ ID NO:61所示的氨基酸序列具有至少约80％序列同一性；以及VL，其包含SEQ ID NO:73所示的氨基酸序列或其变体，所述变体与SEQ ID NO:73所示的氨基酸序列具有至少约80％序列同一性；(ii)VH，其包含氨基酸序列SEQ ID NO:92或其变体，所述变体与氨基酸序列SEQ ID NO:92具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:95或其变体，所述变体与氨基酸序列SEQ ID NO:95具有至少约80％序列同一性；(iii)VH，其包含氨基酸序列SEQ ID NO:93或其变体，所述变体与氨基酸序列SEQ ID NO:93具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:96或其变体，所述变体与氨基酸序列SEQ ID NO:96具有至少约80％序列同一性；(iv)VH，其包含氨基酸序列SEQ ID NO:92或其变体，所述变体与氨基酸序列SEQ ID NO:92具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:96或其变体，所述变体与氨基酸序列SEQ ID NO:96具有至少约80％序列同一性；(v)VH，其包含氨基酸序列SEQ ID NO:94或其变体，所述变体与氨基酸序列SEQ ID NO:94具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:97或其变体，所述变体与氨基酸序列SEQ ID NO:97具有至少约80％序列同一性；(vi)VH，其包含氨基酸序列SEQ ID NO:94或其变体，所述变体与氨基酸序列SEQ ID NO:94具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:98或其变体，所述变体与氨基酸序列SEQ ID NO:98具有至少约80％序列同一性；(vii)VH，其包含氨基酸序列SEQ ID NO:93或其变体，所述变体与氨基酸序列SEQ ID NO:93具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:98或其变体，所述变体与氨基酸序列SEQ ID NO:98具有至少约80％序列同一性；(viii)VH，其包含氨基酸序列SEQ ID NO:92或其变体，所述变体与氨基酸序列SEQ ID NO:92具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:98或其变体，所述变体与氨基酸序列SEQ ID NO:98具有至少约80％序列同一性；(ix)VH，其包含氨基酸序列SEQ ID NO:94或其变体，所述变体与氨基酸序列SEQ ID NO:94具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:99或其变体，所述变体与氨基酸序列SEQ ID NO:99具有至少约80％序列同一性；或(x)VH，其包含氨基酸序列SEQ ID NO:92或其变体，所述变体与氨基酸序列SEQ ID NO:92具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:99或其变体，所述变体与氨基酸序列SEQ ID NO:99具有至少约80％序列同一性。
在一些实施例中，分离的抗LIGHT抗体与人LIGHT的结合的Kd值为0.1pM至约10nM。
在一些实施例中，提供一种分离的抗LIGHT抗体，其与上述任一种分离的抗LIGHT抗体竞争与LIGHT的特异性结合。在一些实施例中，提供一种分离的抗LIGHT抗体，其与上述任一种分离的抗LIGHT抗体特异性地结合相同的表位。
在一些实施例中，如上所述任一种分离的抗LIGHT抗体，所述分离的抗LIGHT抗体包含Fc片段。在一些实施例中，所述分离的抗LIGHT抗体是全长的IgG抗体。在一些实施例中，所述分离的抗LIGHT抗体是全长的IgG1、IgG2、IgG3或IgG4抗体。在一些实施例中，所述分离的抗LIGHT抗体是嵌合的、全人的或人源化的抗体。在一些实施例中，所述分离的抗LIGHT抗体是抗原结合片段，所述抗原结合片段选自Fab、Fab’、F(ab)’2、Fab’-SH、单链Fv(scFv)、Fv片段、dAb、Fd、纳米抗体(nanobody)、双链抗体(diabody)和线性抗体。
在一些实施例中，提供一种分离的核酸分子，所述核酸分子编码如上所述任一种抗LIGHT抗体。在一些实施例中，提供一种载体，所述载体包含如上所述任一种核酸分子。在一些实施例中，提供一种宿主细胞，所述宿主细胞包含如上所述任一种抗LIGHT抗体、如上所述任一种核酸分子或如上所述任一种载体。在一些实施例中，提供一种制备抗LIGHT抗体的方法，其包含：a)在能有效表达抗LIGHT抗体的条件下培养上述任一种宿主细胞；和b)从宿主细胞中获得表达的抗LIGHT抗体。
在一些实施例中，提供一种治疗所需个体疾病或病症的方法，包括向所述个体施用有效量的如上所述的任一种抗LIGHT抗体。在一些实施例中，提供如上所述的任一种抗LIGHT抗体在制备用于治疗所需个体疾病或病症的药物组合物中的用途。在一些实施例中，提供如上所述的任一种抗LIGHT抗体或包含抗LIGHT抗体的药物组合物在制备用于治疗疾病或病症的药物中的用途。在一些实施例中，所述疾病或病症与LIGHT信号通路有关，包括自身免疫性疾病和/或炎症性疾病或病症。在一些实施例中，所述疾病或病症选自例如，炎性肠道疾病(IBD)、克罗恩疾病、溃疡性结肠炎、强直性脊柱炎、异位性皮炎、类风湿性关节炎、细支气管炎、移植排斥反应、同种移植排斥反应、移植物抗宿主病(GVHD)、哮喘、嗜酸性食管炎、急性呼吸窘迫综合征(ARDS)、慢性心脏衰竭、慢性阻塞性肺病(COPD)、败血性休克、纤维化疾病、皮肤纤维化、特发性肺纤维化、肾纤维化、慢性肾病、系统性硬化、多发性硬化症、斯耶格伦氏综合征、狼疮、气道炎症、银屑病、肝炎、乳糜泻、原发性胆汁肝硬化、自身免疫性溶血性贫血、自身免疫性新生儿血小板减少症、原发性血小板减少性紫癜、非酒精性脂肪肝、COVID19。
同时还提供包含如上所述的任一种抗LIGHT抗体的药物组合物、试剂盒以及生产制品。
附图说明
图1所示为ELISA分析的嵌合抗LIGHT抗体与人LIGHT的结合亲和力。图1A所示为示例性嵌合抗LIGHT抗体LT-m17、LT-m18与人LIGHT的结合亲和力。图1B所示为示例性嵌合抗LIGHT抗体LT-m31、LT-m 33、LT-m37与人LIGHT的结合亲和力。图1C所示为示例性嵌合抗LIGHT抗体LT-m55、LT-m58、LT-m64、LT-m85与人LIGHT的结合亲和力。
图2所示为ELISA分析的嵌合抗LIGHT抗体与食蟹猴LIGHT的交叉结合活性。图2A所示为示例性嵌合抗LIGHT抗体LT-m17、LT-m18与食蟹猴LIGHT的交叉结合活性。图2B所示为示例性嵌合抗LIGHT抗体LT-m31、LT-m33、LT-m37与食蟹猴LIGHT的交叉结合活性。图2C所示为示例性嵌合抗LIGHT抗体LT-m55、LT-m58、LT-m64、LT-m85与食蟹猴LIGHT的交叉结合活性。
图3A所示为示例性嵌合抗LIGHT抗体LT-m17、LT-m31、LT-m33、LT-m37对游离LIGHT激活LTβR报告基因的抑制活性。图3B所示为示例性嵌合抗LIGHT抗体LT-m55、LT-m58、LT-m64、LT-m85对游离LIGHT激活LTβR报告基因的抑制活性。
图4A所示为示例性嵌合抗LIGHT抗体LT-m17、LT-m31、LT-m33、LT-m37对细胞LIGHT激活LTβR报告基因的抑制活性。图4B所示为示例性嵌合抗LIGHT抗体LT-m55、LT-m58、LT-m64对细胞LIGHT激活LTβR报告基因的抑制活性。图4C所示为示例性嵌合抗LIGHT抗体LT-m85对细胞LIGHT激活LTβR报告基因的抑制活性。
图5A所示为示例性嵌合抗LIGHT抗体LT-m17、LT-m31、LT-m33、LT-m37对游离LIGHT激活HVEM报告基因的抑制活性。图5B所示为示例性嵌合抗LIGHT抗体LT-m55、LT-m64、LT-m85对游离LIGHT激活HVEM报告基因的抑制活性。图5C所示为示例性嵌合抗LIGHT抗体LT-m58对游离LIGHT激活HVEM报告基因的抑制活性。
图6所示为ELISA分析的人源化抗LIGHT抗体与人LIGHT的结合亲和力。图6A所示为示例性人源化抗LIGHT抗体hum_LT-m37-1～hum_LT-m37-6与人LIGHT的结合亲和力。图6B所示为示例性人源化抗LIGHT抗体hum_LT-m37-7～hum_LT-m37-12与人LIGHT的结合亲和力。图6C所示为示例性人源化抗LIGHT抗体hum_LT-m37-13～hum_LT-m37-16与人LIGHT的结合亲和力。
图7所示为ELISA分析的人源化抗LIGHT抗体阻断LIGHT与LTβR结合的活性。图7A所示为ELISA分析的示例性人源化抗LIGHT抗体hum_LT-m37-1、hum_LT-m37-2、hum_LT-m37-4、hum_LT-m37-9阻断LIGHT与LTβR结合的活性。图7B所示为ELISA分析的示例性人源化抗LIGHT抗体hum_LT-m37-5、hum_LT-m37-6、hum_LT-m37-7、hum_LT-m37-8、hum_LT-m37-11、hum_LT-m37-12阻断LIGHT与LTβR结合的活性。图7C所示为ELISA分析的示例性人源化抗LIGHT抗体hum_LT-m37-13、hum_LT-m37-14、hum_LT-m37-15、hum_LT-m37-16阻断LIGHT与LTβR结合的活性。
图8A所示为示例性人源化抗LIGHT抗体hum_LT-m37-1～hum_LT-m37-6对游离LIGHT激活LTβR报告基因的抑制活性。图8B所示为示例性人源化抗LIGHT抗体hum_LT-m37-7～hum_LT-m37-12对游离LIGHT激活LTβR报告基因的抑制活性。图8C所示为示例性人源化抗LIGHT抗体hum_LT-m37-13～hum_LT-m37-16对游离LIGHT激活LTβR报告基因的抑制活性。
图9A所示为示例性人源化抗LIGHT抗体hum_LT-m37-1～hum_LT-m37-6对细胞LIGHT激活LTβR报告基因的抑制活性。图9B所示为示例性人源化抗LIGHT抗体hum_LT-m37-7～hum_LT- m37-12对细胞LIGHT激活LTβR报告基因的抑制活性。图9C所示为示例性人源化抗LIGHT抗体hum_LT-m37-13～hum_LT-m37-16对细胞LIGHT激活LTβR报告基因的抑制活性。
图10A所示为示例性人源化抗LIGHT抗体hum_LT-m37-1～hum_LT-m37-6对游离LIGHT激活HVEM报告基因的抑制活性。图10B所示为示例性人源化抗LIGHT抗体hum_LT-m37-14、hum_LT-m37-15、hum_LT-m37-16对游离LIGHT激活HVEM报告基因的抑制活性。
图11所示为示例性人源化抗LIGHT抗体hum_LT-m37-13、hum_LT-m37-14、hum_LT-m37-15、hum_LT-m37-16对LIGHT诱导BEAS-2B支气管上皮细胞产生MMP-9的抑制活性。
图12所示为示例性人源化抗LIGHT抗体hum_LT-m37-13、hum_LT-m37-14、hum_LT-m37-15、hum_LT-m37-16对LIGHT刺激CD3+T细胞活化增殖的抑制活性。
图13所示为在LPS诱导的小鼠ARDS模型中示例性抗LIGHT抗体对白细胞水平的抑制活性。图13A所示为在LPS诱导的小鼠ARDS模型中示例性抗LIGHT抗体LT-m17、hum_LT-m37-12对总白细胞水平的抑制活性。图13B所示为在LPS诱导的小鼠ARDS模型中示例性抗LIGHT抗体LT-m17、hum_LT-m37-12对中间细胞水平的抑制活性。图13C所示为在LPS诱导的小鼠ARDS模型中示例性抗LIGHT抗体LT-m17、hum_LT-m37-12对淋巴细胞水平的抑制活性。图13D所示为在LPS诱导的小鼠ARDS模型中示例性抗LIGHT抗体LT-m17、hum_LT-m37-12对中性粒细胞水平的抑制活性。
本申请的详细描述
本申请一方面提供抗LIGHT抗体分子。通过构建的scFv噬菌体库筛选、亲和力成熟以及适当设计的生物化学及生物学实验的组合，已经鉴定出能够结合人LIGHT并抑制人LIGHT与其受体作用的高效抗体分子。本文给出的结果表明，与已知抗LIGHT抗体F19(又称为CERC-002,Quisovalimab；Avalo Therapeutics公司)相比，本申请中的抗体结合LIGHT的不同区域或表位，并且令人惊讶地是，在各种生物学实验中证明了本申请中的抗体甚至比F19更有效。
本申请所提供的抗LIGHT抗体包括，例如，全长抗LIGHT抗体、抗LIGHT单链抗体(scFvs)、抗LIGHT Fc融合蛋白、多特异性(如双特异性)抗LIGHT抗体、抗LIGHT免疫偶联物以及诸如此类的。
另一方面，本申请提供抗LIGHT抗体，所述抗LIGHT抗体包含：重链可变结构域(VH)，所述VH包含：重链互补决定区(HC-CDR)1，其包含GYFIN(SEQ ID NO:1)；HC-CDR2，其包含RIYPYNVX1TFYNQNFKG(SEQ ID NO:45)，其中X1为D或N；和HC-CDR3，其包含GTHYYGSSGAMDY(SEQ ID NO:16)；以及轻链可变结构域(VL)，所述VL包含：轻链互补决定区(LC-CDR)1，其包含KASQNVGTAVA(SEQ ID NO:23)；LC-CDR2，其包含SASNRYT(SEQ ID NO:30)；和LC-CDR3，其包含QQYSSYPYT(SEQ ID NO:37)。
另一方面，本申请提供抗LIGHT抗体，所述抗LIGHT抗体包含：重链可变结构域(VH)，所述VH包含：重链互补决定区(HC-CDR)1，其包含GYFMN(SEQ ID NO:2)；HC-CDR2，其 包含RIYPYSGDTFYNQKFNN(SEQ ID NO:10)；和HC-CDR3，其包含SEHFGRNYGTGAVDY(SEQ ID NO:17)；以及轻链可变结构域(VL)，所述VL包含：轻链互补决定区(LC-CDR)1，其包含RSSQGLVHSNGNTYLH(SEQ ID NO:24)；LC-CDR2，其包含KVSNRFS(SEQ ID NO:31)；和LC-CDR3，其包含SQSTHVPYT(SEQ ID NO:38)。
另一方面，本申请提供抗LIGHT抗体，所述抗LIGHT抗体包含：重链可变结构域(VH)，所述VH包含：重链互补决定区(HC-CDR)1，其包含GYFMN(SEQ ID NO:2)；HC-CDR2，其包含RIYPYSGDTFYNQKFNN(SEQ ID NO:10)；和HC-CDR3，其包含SEHFGRNYGTGAVDY(SEQ ID NO:17)；以及轻链可变结构域(VL)，所述VL包含：轻链互补决定区(LC-CDR)1，其包含RSSQSLVHSNGNTYLH(SEQ ID NO:25)；LC-CDR2，其包含KVSNRFS(SEQ ID NO:31)；和LC-CDR3，其包含SQSTHVPLT(SEQ ID NO:39)。
另一方面，本申请提供抗LIGHT抗体，所述抗LIGHT抗体包含：重链可变结构域(VH)，所述VH包含：重链互补决定区(HC-CDR)1，其包含NYYVY(SEQ ID NO:3)；HC-CDR2，其包含EINPTNGDPNFNEKFKS(SEQ ID NO:11)；和HC-CDR3，其包含SNWDYGNAMDF(SEQ ID NO:18)；以及轻链可变结构域(VL)，所述VL包含：轻链互补决定区(LC-CDR)1，其包含KASQSVDFDGDGYMN(SEQ ID NO:26)；LC-CDR2，其包含KASHLDS(SEQ ID NO:32)；和LC-CDR3，其包含QQSIEDPLT(SEQ ID NO:40)。
另一方面，本申请提供抗LIGHT抗体，所述抗LIGHT抗体包含：重链可变结构域(VH)，所述VH包含：重链互补决定区(HC-CDR)1，其包含NYYVY(SEQ ID NO:3)；HC-CDR2，其包含EINPTNGDPNFNEKFKS(SEQ ID NO:11)；和HC-CDR3，其包含SNWDYGNAMDF(SEQ ID NO:18)；以及轻链可变结构域(VL)，所述VL包含：轻链互补决定区(LC-CDR)1，其包含KASQSVDFDGDGYMN(SEQ ID NO:26)；LC-CDR2，其包含KASHLDS(SEQ ID NO:32)；和LC-CDR3，其包含QQSIEDPFT(SEQ ID NO:41)。
另一方面，本申请提供抗LIGHT抗体，所述抗LIGHT抗体包含：重链可变结构域(VH)，所述VH包含：重链互补决定区(HC-CDR)1，其包含NYGMN(SEQ ID NO:4)；HC-CDR2，其包含WINTYTGEPTYADDFKG(SEQ ID NO:12)；和HC-CDR3，其包含DNWDGKGMDY(SEQ ID NO:19)；以及轻链可变结构域(VL)，所述VL包含：轻链互补决定区(LC-CDR)1，其包含KASQDVDTAVA(SEQ ID NO:27)；LC-CDR2，其包含WASTRHT(SEQ ID NO:33)；和LC-CDR3，其包含HQYGSYPLT(SEQ ID NO:42)。
另一方面，本申请提供抗LIGHT抗体，所述抗LIGHT抗体包含：重链可变结构域(VH)，所述VH包含：重链互补决定区(HC-CDR)1，其包含TYYMY(SEQ ID NO:5)；HC-CDR2，其包含EINPTNGGTIFNEKFKT(SEQ ID NO:13)；和HC-CDR3，其包含GNWPYWSFDV(SEQ ID NO:20)；以及轻链可变结构域(VL)，所述VL包含：轻链互补决定区(LC-CDR)1，其包含KASQSVDFDGDNYMN(SEQ ID NO:28)；LC-CDR2，其包含AASNLDS(SEQ ID NO:34)；和LC-CDR3，其包含QQSIEDPWT(SEQ ID NO:43)。
另一方面，本申请提供抗LIGHT抗体，所述抗LIGHT抗体包含：重链可变结构域(VH)，所述VH包含：重链互补决定区(HC-CDR)1，其包含DHIMN(SEQ ID NO:6)；HC-CDR2，其包含RIYPVSGETNYNQKFMG(SEQ ID NO:14)；和HC-CDR3，其包含GSYYWNAMDY(SEQ ID NO:21)；以及轻链可变结构域(VL)，所述VL包含：轻链互补决定区(LC-CDR)1，其包含KASQSVDFDGDSYMN(SEQ ID NO:29)或KASQSVDFDGESYMN(SEQ ID NO:83)；LC-CDR2，其包含SASNLES(SEQ ID NO:35)；和LC-CDR3，其包含QQSIEDPWT(SEQ ID NO:43)。
另一方面，本申请提供抗LIGHT抗体，所述抗LIGHT抗体包含：重链可变结构域(VH)，所述VH包含：重链互补决定区(HC-CDR)1，其包含SYNVH(SEQ ID NO:7)；HC-CDR2，其包含AVYPGNGDTSYNQKFKG(SEQ ID NO:15)；和HC-CDR3，其包含GSYYYTSSYFDH(SEQ ID NO:22)；以及轻链可变结构域(VL)，所述VL包含：轻链互补决定区(LC-CDR)1，其包含KASQSVDFDGDSYMN(SEQ ID NO:29)；LC-CDR2，其包含TASNLES(SEQ ID NO:36)；和LC-CDR3，其包含QQSYEDPFT(SEQ ID NO:44)。
同时还提供编码抗LIGHT抗体的核酸，包含抗LIGHT抗体的组合物，以及制备和使用抗LIGHT抗体的方法。
定义
如本文所述，“治疗(treatment)”或“治疗(treating)是一种获得有益的或期望的结果的方法，包括临床结果。鉴于本申请的目的，所述有益的或期望的临床结果，包括但不限于以下一种或多种：缓解由疾病引起的一种或多种症状，减轻疾病程度，稳定疾病(例如，预防或延迟疾病恶化)，预防或延迟疾病的扩散(例如，转移)，预防或延迟疾病复发，延迟或减缓疾病进展，改善疾病状态，缓解疾病(部分或全部)，减少治疗疾病所需的一种或多种其他药物的剂量，延迟疾病进展，改善或提高生活质量，增加体重，和/或延长生存期。同时，“治疗”还包括疾病病理结果的减少(例如，对哮喘而言，强力呼气容积)。本申请的方法考虑了这些治疗的任何一个或多个方面。
术语“抗体”包括全长抗体及其抗原结合片段。全长抗体包括两条重链和两条轻链。轻链和重链的可变区负责抗原的结合。两条链中的可变区通常包括3个高变的环，被称为互补决定区(CDRs)(轻链(LC)CDRs包括LC-CDR1、LC-CDR2和LC-CDR3，重链(HC)CDRs包括HC-CDR1、HC-CDR2和HC-CDR3)。本文所披露的抗体或抗原结合片段的CDR边界可以通过Kabat，Chothia或Al-Lazikani惯例来定义或识别(Al-Lazikani 1997；Chothia 1985；Chothia 1987；Chothia 1989；Kabat 1987；Kabat 1991)。重链或轻链的3个CDR区插入到被称为框架区(FRs)的侧翼区段之间，所述框架区比CDR区具有更高的保守性，并形成支撑高变环的支架。重链和轻链的恒定区并不参与抗原结合，但展示出多种效应功能。抗体是基于它们重链恒定区的氨基酸序列进行分类的。抗体的五种主要类别或同种型是IgA、IgD、IgE、IgG和IgM，其特征在于分别具有 α、δ、ε、γ和μ型重链。几种主要的抗体类别被分为亚类，如IgG1(γ1重链)、IgG2(γ2重链)、IgG3(γ3重链)、IgG4(γ4重链)、IgA1(α1重链)或IgA2(α2重链)。
如本文所述，术语“抗原结合片段”包括抗体片段，例如，双链抗体(diabody)、Fab、Fab’、F(ab’)2、Fv片段、二硫键稳定的Fv片段(dsFv)、(dsFv)2、双特异性dsFv(dsFv-dsFv’)、二硫键稳定的双链抗体(ds双链抗体)、单链Fv(scFv)、scFv二聚体(二价双链抗体)，由包含一个或多个CDRs的抗体片段组成的多特异性抗体、单域抗体、纳米抗体(nanobody)、域抗体、二价域抗体或者能够与抗原结合但不包含完整抗体结构的任何其他抗体片段。抗原结合片段能够与亲本抗体或亲本抗体片段(如亲本scFv)结合相同的抗原。抗原结合片段还包括包含上述抗体片段的融合蛋白。在一些实施例中，抗原结合片段可能包括来自特定人抗体的一个或多个CDRs，该CDRs被移植到来自一个或多个不同人抗体的框架区。
如本文所述，术语“表位”是指抗体或抗体部分结合的抗原上特定的原子或氨基酸组。如果两种抗体或抗体部分表现出与某抗原竞争性结合，则它们可能结合抗原上的相同表位。
如本文所用，当第一抗体在等摩尔浓度下抑制第二抗体与LIGHT靶标结合至少50％(例如至少55％、60％、65％、70％、75％、80％、85％、90％、95％、98％或99％)时，第一抗体与第二抗体“竞争”结合LIGHT靶标，反之亦然。PCT出版物WO 03/48731描述了基于交叉竞争的高通量抗体“表位归类”方法。
如本文所述，术语“特异性地结合”、“特异性地识别”或“对..来说是特异性的”是指可测量的和可再现的相互作用，例如抗体与靶标的结合可以确定在异质分子群，包括生物分子中存在该靶标。例如，抗体能够特异性地识别某靶标(可以是表位)是指，与其它靶标结合相比，该抗体与该靶标的结合具有更高的亲和力，亲合力，更容易和/或更持久。在一些实施例中，特异性地识别抗原的抗体与抗原的一个或多个抗原决定簇反应，其结合亲和力是其与其它靶标结合亲和力的至少10倍。
如本文所述，一种“分离的”抗LIGHT抗体是指一种抗LIGHT抗体，其(1)与天然存在的蛋白无关，(2)不含相同来源的其他蛋白，(3)由不同种属的细胞所表达，或(4)自然界中不存在。
如本文所述，术语“分离的核酸”，是指基因组、cDNA或合成来源的核酸或其组合。根据其来源，所述“分离的核酸”是指(1)与自然界中发现的“分离的核酸”中的全部或部分多核苷酸无关，(2)可与自然状态下不与之相连的多核苷酸可操作性地连接，或(3)在自然界中不作为较长序列的一部分而存在。
如本文所用，术语“CDR”或“互补决定区”意指重链和轻链多肽的可变结构域内发现的非连续抗原结合位点。在文献Kabat et al.,J.Biol.Chem.252:6609-6616(1977)；Kabat et al.,U.S.Dept.of Health and Human Services,“Sequences of proteins of immunological interest”(1991)；Chothia et al.,J.Mol.Biol.196:901-917(1987)；Al-Lazikani B.et al.,J.Mol.Biol.,273:927-948(1997)；MacCallum et al.,J.Mol.Biol.262:732-745(1996)；Abhinandan and Martin,Mol.Immunol.,45:3832- 3839(2008)；Lefranc M.P.et al.,Dev.Comp.Immunol.,27:55-77(2003)；和Honegger and Plückthun,J.Mol.Biol.,309:657-670(2001)中已经描述这些特殊的区域，其中当彼此之间互相比较时，这些定义包括氨基酸残基的重合或子集。然而，采用任何一种定义方式来指示抗体或移植抗体或其变体的CDR，均包括在本文所定义和使用的术语范围之内。表1中列了由上述引用的各篇参考文献所定义的CDR所包括的氨基酸残基的位置，以示比较。CDR预测的算法和结合界面在本领域是已知的，包括，例如Abhinandan and Martin,Mol.Immunol.,45:3832-3839(2008)；Ehrenmann F.et al.,Nucleic Acids Res.,38:D301-D307(2010)；和Adolf-Bryfogle J.et al.,Nucleic Acids Res.,43:D432-D438(2015)中均有描述。本段中所引用的参考文献的内容以其整体引用并入本文中，以用于本申请和可能包含在本文中的一个或多个权利要求中。
表1:CDR定义

1氨基酸残基编号参照上述Kabat et al.中的命名方法
2氨基酸残基编号参照上述Chothia et al.中的命名方法
3氨基酸残基编号参照上述MacCallum et al.中的命名方法
4氨基酸残基编号参照上述Lefranc et al.中的命名方法
5氨基酸残基编号参照上述Honegger and Plückthun中的命名方法
术语“嵌合抗体”是指，重链和/或轻链的一部分与来自特定种属或属于特定抗体种类或亚类的抗体中的相应序列一致或具有同源性，而这个(些)链的剩余部分与来自另一种属或属于其它抗体种类或亚类的抗体中的相应序列一致或具有同源性的抗体，以及此类抗体的片段，只要其具有本申请中的生物学活性(见U.S.Patent No.4,816,567；and Morrison et al.,Proc.Natl.Acad.Sci.USA,81:6851-6855(1984))。
“Fv”是包含完整抗原识别及结合位点的最小抗体片段。该片段是由一个重链可变结构域和一个轻链可变结构域紧密非共价连接形成的二聚体。通过这两个域的折叠衍生出6个高变环(轻链和重链中各3个环)，所述高变环为抗体提供了用于结合抗原的氨基酸残基，并且赋予抗体与抗原结合的特异性。然而，即使单个可变结构域(或Fv片段的一半，其仅包含对抗原具有特异性的3个CDRs)也具有识别和结合抗原的能力，尽管其亲和力低于完整的结合位点。
“单链Fv”，也可简写成“sFv”或“scFv”，是包含被连接成单一多肽链的VH和VL抗体域的抗体片段。在一些实施例中，scFv多肽进一步包括VH和VL域之间的连接多肽，该连接多肽使得scFv形成抗原结合的理想结构。关于scFv的概述，见Pluckthun in The Pharmacology of Monoclonal Antibodies,vol.113,Rosenburg and Moore eds.,Springer-Verlag,New York,pp.269-315(1994)。
术语“双链抗体(diabody)”是在VH和VL域之间采用短接头(例如5～10个残基)，构建scFv片段(见上段内容)制备而成的一种小抗体片段，这样就使得可变结构域在链间而不是链内进行配对，产生一个双价片段，即具有两个抗原结合位点的片段。双特异性的双链抗体是两个“交叉”scFv片段的异二聚体，其中两个抗体的VH和VL域位于不同的多肽链上。在EP 404,097；WO 93/11161；Hollinger et al.,Proc.Natl.Acad.Sci.USA,90:6444-6448(1993)中全面描述了双链抗体。
非人源(如啮齿类)抗体的“人源化”形式是嵌合抗体，其包括最少的来自非人源抗体的序列。大多数情况下，人源化抗体是人源免疫球蛋白(受体抗体)，其中受体抗体的高变区(HVR)残基被来自非人源种属例如小鼠、大鼠、兔或非人类哺乳动物的且具有理想的抗体特异性，亲和力和性能的高变区残基所取代(供体抗体)。在某些情况下，人源免疫球蛋白框架区中的残基被相应的非人源残基所取代。另外，人源化抗体可以包括在受体抗体或供体抗体中均不存在的残基。这些修饰能够进一步改善抗体的性能。通常，人源化抗体会包含基本上所有，至少一个，通常两个可变结构域，其中所有或基本上所有的高变环均与非人免疫球蛋白的高变环相对应，以及所有或基本上所有的框架区均是人免疫球蛋白序列。人源抗体任选地也还包括免疫球蛋白恒定区(Fc)的至少一部分，通常是人免疫球蛋白的恒定区。具体细节可以参考Jones et al.,Nature 321:522-525(1986)；Riechmann et al.,Nature 332:323-329(1988)；和Presta,Curr.Op.Struct.Biol.2:593-596(1992)。
本文所鉴定的多肽和抗体序列的“氨基酸序列同一性百分比(％)”或“同源性”被定义：在认为保守性取代属于序列同一性的一部分的情况下进行序列对比，候选序列与待比较多肽序列中相同氨基酸残基所占的百分比。可以通过本领域技术范围内的多种比对方式来确定氨基酸序列同一性百分比，例如，使用如BLAST、BLAST-2、ALIGN、Megalign(DNASTAR)、或MUSCLE软件等可公开获得的计算机软件。本领域技术人员可以确定用于测量比对的合适的参数，包括在所比较序列的全长上实现最大化比对所需的任何算法。然而，为了本文的目的，氨基酸序列同一性百分比数值是使用序列比对电脑程序MUSCLE(Edgar,R.C.,Nucleic Acids Research 32(5):1792-1797,2004；Edgar,R.C.,BMC Bioinformatics 5(1):113,2004)生成的。
术语“Fc受体”或“FcR”用于描述结合抗体Fc区的受体。在一些实施例中，本申请所述的FcR是结合IgG抗体(一种γ受体)的FcR，包括FcγRI、FcγRII和FcγRIII亚类的受体，包括这些受体的等位基因变体和可变剪接形式。FcγRII受体包括FcγRIIA(“激活受体”)和FcγRIIB(“抑制受体”)，它们具有相似的氨基酸序列，主要在细胞质结构域有所不同。激活受体FcγRIIA的胞质结构域中含有免疫受体酪氨酸活化基序(ITAM)。抑制受体FcγRIIB的胞质结构域中含有免疫受体酪氨酸抑制基序(ITIM)(见M.inAnnu.Rev.Immunol.15:203-234(1997))。所述术语 还包括同种异型，例如FcγRIIIA同种异型：FcγRIIIA-Phe158、FcγRIIIA-Val158、FcγRIIA-R131和/或FcγRIIA-H131。在Ravetch and Kinet,Annu.Rev.Immunol 9:457-92(1991)和Capel et al.,Immunomethods 4:25-34(1994)；以及de Haas et al.,J.Lab.Clin.Med.126:330-41(1995)中对FcRs进行了描述。本申请中术语FcR涵盖其他类型的FcRs，包括将来鉴定的FcRs。术语FcR同时还包括新生儿受体FcRn，其负责向新生儿转移母体IgGs(Guyer et al.,J.Immunol.117:587(1976)以及Kim et al.,J.Immunol.24:249(1994))。
术语“FcRn”指新生儿Fc受体(FcRn)。FcRn与主要组织相容性复合体(MHC)在结构上相似，由α链非共价结合到β2微球蛋白上组成。新生儿Fc受体FcRn的多种功能在Ghetie and Ward(2000)Annu.Rev.Immunol.18,739-766.中进行了综述。FcRn在免疫球蛋白IgGs从母体向新生儿的被动转运和调控血清IgG水平中起到重要作用。FcRn作为一种救助受体，可以在细胞内和细胞间以完整的形式结合和运输胞吞化的IgG，并使它们免于经受默认的降解途径。
人IgG重链恒定区的“CH1结构域”通常从118位氨基酸延伸到215位氨基酸(EU编号系统)。
“铰链区”通常被定义为从人IgG1的216位Glu延伸到230位Pro(Burton,Molec.Immunol.22:161-206(1985))。通过将形成重链间二硫键的第一个和最后一个半胱氨酸残基置于与IgG1相同位置后，可以使得其他IgG同种型的铰链区与IgG1序列比对。
人IgG Fc区的“CH2结构域”通常从231位氨基酸延伸到340位氨基酸。CH2结构域的独特之处在于，它不会与另一个区域紧密配对，而是在完整的天然IgG分子的两个CH2结构域之间插入了两条N端连接的支链糖链。据推测，糖类可能作为域与域间配对的替代，有助于保持CH2结构域稳定。Burton,Molec.Immunol.22:161-206(1985)。
“CH3”结构域包括在Fc区内从C末端残基延伸到CH2结构域(从341位氨基酸到抗体序列的C末端，通常为IgG的第446或447位氨基酸残基)。
“功能性Fc片段”具有天然Fc区序列所具有的“效应功能”。示例性的“效应功能”包括C1q结合；补体依赖的细胞毒作用(CDC)；Fc受体结合；抗体依赖的细胞介导的细胞毒作用(ADCC)；吞噬作用；细胞表面受体的下调(如B细胞受体；BCR)等。这类效应功能通常需要Fc区与结合结构域(如抗体可变区)结合，并且可以使用本领域公知的多种实验方法进行评估。
具有“改变的”FcR结合亲和力或ADCC活性的IgG Fc变体的抗体，与亲本多肽或包含天然Fc序列的多肽相比，其FcR结合活性和/或ADCC活性增强或减弱。表现出与FcR“结合增强”的Fc变体与亲本多肽或包含天然IgG Fc序列的多肽相比，其与至少一种FcR具有更高的结合亲和力(例如更低的表观Kd或IC50值)。在一些实施例中，与亲本多肽相比，结合能力增强3倍，例如5、10、25、50、60、100、150、200，甚至高达500倍或结合力提高25％到1000％。表现出与FcR“结合降低”的Fc变体，与亲本多肽相比，其与至少一种FcR具有更低的亲和力(例如更高的表观Kd或IC50值)。与亲本多肽相比，其结合能力下降40％或更多。
“抗体依赖的细胞介导的细胞毒作用”或“ADCC”是一种细胞毒性形式，指分泌型的Ig与存在于某些细胞毒性细胞(例如自然杀伤细胞(NK)、中性粒细胞、和巨噬细胞)上的Fc受体(FcRs)结合，使这些细胞毒性效应细胞能够特异性结合携带抗原的靶细胞，随后使用细胞毒素杀死靶细胞。抗体“武装”细胞毒性细胞并且是这种杀伤所必需的。介导ADCC的主要细胞类型中，NK细胞只表达FcγRIII，而单核细胞表达FcγRI、FcγRII和FcγRIII。在Ravetch and Kinet,Annu.Rev.Immunol 9:457-92(1991)第464页的Table 3中总结了在造血细胞上FcR的表达。评估目标分子的ADCC活性，可以进行体外ADCC实验，在美国专利No.5,500,362或5,821,337中进行了描述。适用于此类实验的效应细胞包括外周血单核细胞(PBMC)和自然杀伤性细胞(NK)。可选地，或者此外，目标分子的ADCC活性也可以在体内进行评估，例如在如Clynes et al.PNAS(USA)95:652-656(1998)中所公开的动物模型中进行了描述。
包含Fc区变体的多肽与包含野生型IgG Fc多肽或亲本多肽相比，在人体效应细胞存在下表现出“增强的ADCC活性”或能够更有效的介导ADCC效应，所述包含Fc区变体的多肽在实验时与包含野生型IgG Fc多肽(或亲本多肽)数量上基本相同时，无论在体外或体内均能更有效的介导ADCC。通常采用本领域已知的任何体外ADCC实验方法来鉴定此类变体，例如用于鉴定ADCC活性的实验或方法，例如在动物模型中等。在一些实施例中，此类变体与野生型Fc(或亲代多肽)相比，介导ADCC的效率提高5到100倍，例如25到50倍。
“补体依赖的细胞毒作用”或“CDC”是指在补体存在的情况下裂解靶细胞。经典的补体途径的激活是由补体系统第一组分(C1q)与结合同源抗原的抗体(具有适宜结构的亚类)相结合而启动的。为了评估补体激活，可以进行CDC实验，如Gazzano-Santoro et al.,J.Immunol.Methods 202:163(1996)中所描述的。在美国专利No.6,194,551B1和WO99/51642中描述了具有改变的Fc区氨基酸序列并增加或降低的C1q结合能力的多肽变体。这些专利出版物的内容通过引用明确地并入本文中。另见Idusogie et al.J.Immunol.164:4178-4184(2000)。
除非另有说明，一种“编码氨基酸序列的核苷酸序列”包括相互之间互为简并形式且编码相同氨基酸序列的所有核苷酸序列。编码蛋白质或RNA的核苷酸序列也可包括内含子，例如编码蛋白质的核苷酸序列在某些形式中包含内含子。
术语“可操作性地连接”是指调控序列与异源核苷酸序列之间的功能性连接，从而使后者表达。例如，当第一个核苷酸序列与第二个核苷酸序列处于功能性关系时，第一个核苷酸序列与第二个核苷酸序列为可操作性地连接。例如，如果启动子影响编码序列的转录或表达，该启动子与编码序列为可操作性地连接。通常，可操作性连接的DNA序列是连续的，并且在必要时，可以在同一个阅读框中连接两个蛋白质编码区。
“同源”是指两个多肽之间或两个核酸分子之间的序列相似性或序列同一性。如果两个比较序列的同一位置为相同的碱基或氨基酸单体亚基时，例如两个DNA分子的同一位置均为腺嘌呤，则这两个DNA分子在该位置是同源的。两个序列间的同源百分比是指两个序列中共有的匹配或同源位置的数量与位置总数之比再乘以100所得函数。例如，两个序列中如果10个位置中有6个位置是 相匹配或同源的，则这两个序列的同源性为60％。举例来说，DNA序列ATTGCC和TATGGC具有50％的同源性。通常来说，在比对两个序列时，以得到最大同源性为目的来进行对比。
本文所公开的抗LIGHT抗体或组合物的“有效量”是指足以实现特定目的的量。“有效量”可以凭经验和通过已知的与所述目的相关的方法确定。
术语“治疗有效量”是指本文所公开的抗LIGHT抗体或其组合物能够有效治疗个体的疾病或者症状的用量。例如在哮喘的情况中，“哮喘相关参数”作为评价哮喘治疗效果的指标，例如，“哮喘相关参数”包括：(a)1秒内强力呼气容积(FEV1)；(b)呼气流量峰值(PEF)，包括早晨PEF(AM PEF)和晚上PEF(PM PEF)；(c)使用吸入性支气管扩张剂，如沙丁胺醇或左旋沙丁胺醇；(d)五项哮喘控制问卷(ACQ5)得分；(d)夜间觉醒；和(e)22项Sino-Nasal结果测试(SNOT-22)得分。本文所公开的治疗有效量的抗LIGHT抗体或组合物可以使FEV1、AM PEF或PM PEF中的一项或多项从基线增加，和/或使每日沙丁胺醇/左旋沙丁胺醇使用量、ACQ5评分、夜间平均觉醒次数或SNOT-22评分中的一项或多项从基线减少。如本文所使用的术语“基线”，就哮喘相关参数而言，是指患者在服用本发明的药物组合物之前或服用时的哮喘相关参数的数值。在一些实施例中，哮喘相关参数的改善是指FEV1从基线至少增加0.10L。在一些实施例中，哮喘相关参数的改善是指AM PEF从基线增加至少10.0L/min。在一些实施例中，哮喘相关参数的改善是指PM PEF从基线增加至少1.0L/min。在一些实施例中，哮喘相关参数的改善是指从基线开始，每天至少减少1puff(s)沙丁胺醇/左旋沙丁胺醇使用量。在一些实施例中，哮喘相关参数的改善是指ACQ5评分从基线下降至少0.5分。在一些实施例中，哮喘相关参数的改善是指夜间觉醒的次数从基线减少至少0.2次。在一些实施例中，哮喘相关参数的改善是指SNOT-22评分从基线下降至少5分。在一些实施例中，治疗有效量是能够充分控制疾病的量。在一些实施例中，治疗有效量是延长病人生存期的量。在某些实施例中，治疗有效量是改善患者无进展生存的量。
如本文所用的，“药学上可接受的”或“药理学上相容的”是指无生物学活性或者其它不期望性质的材料，例如该材料能够加入到给予患者的药物组合物中，而不会引起显著的不良生物反应，或者，不与组合物中包含的任何其它组分以有害的方式相互作用。药学上可接受的载体或赋形剂优选满足毒理学或制造检测的所需标准和/或包含在美国食品和药品管理局编制的非活性成分指南中。
本文中描述的本申请的实施例应理解为包含“由……组成”和/或“基本上由……组成”的实施例。
本文中提及“约”为一个数值或参数，包含(和描述)针对该值或参数本身的变体。例如，涉及“约X”的描述，包括“X”的描述。
如本文所用的，提及“不是(not)”一个数值或参数，通常表示并描述“除了(other than)”某一数值或参数之外。例如，该方法不能用于治疗X型癌症，意味着该方法通常用于治疗除X型癌症之外的其他类型的癌症。
除非上下文另有明确说明，本文和所述权利要求中所采用的单数形式“一”，“一个”和“该”包括复数对象。
抗LIGHT抗体
一方面，本申请提供特异性结合LIGHT的抗人和/或食蟹猴LIGHT抗体。所述抗LIGHT抗体包括，但不限于，人源化抗体，嵌合抗体，小鼠抗体，人抗体，以及本文所述的包含重链和/或轻链CDRs的抗体分子。一方面，本申请提供与LIGHT结合的分离的抗体。预期的抗LIGHT抗体包括，例如，全长抗LIGHT抗体(如全长IgG1或IgG4)，抗LIGHT单链抗体，抗LIGHT Fc融合蛋白，多特异性(如双特异性)抗LIGHT抗体，抗LIGHT免疫偶联物，以及诸如此类的。在一些实施例中，抗LIGHT抗体是全长抗体(如全长IgG1或IgG4)或其抗原结合片段，其特异性结合LIGHT。在一些实施例中，抗LIGHT抗体是Fab、Fab’、F(ab)’2、Fab’-SH、单链Fv(scFv)、Fv片段、dAb、Fd、纳米抗体(nanobody)、双链抗体(diabody)或线性抗体。在一些实施例中，特异性结合LIGHT的抗体是指抗体与LIGHT结合的亲和力至少是与非靶标结合亲和力的10倍以上(包括例如10、102、103、104、105、106、或107倍)。在一些实施例中，非靶标是指不是LIGHT的抗原。结合亲和力可通过本领域已知的方法来测定，如ELISA，荧光激活细胞分选(FACS)分析或放射免疫沉淀分析(RIA)。Kd值可以通过本领域已知的方法来测定，如表面等离子共振(SPR)技术或生物层干涉技术(BLI)。
尽管本文广泛地讨论了包含人序列的抗LIGHT抗体(例如，包含人CDR序列的人重链和轻链可变结构域)，但同时也考虑了非人抗LIGHT抗体。在一些实施例中，非人抗LIGHT抗体包括本文所述的抗LIGHT抗体的人CDR序列和非人框架区序列，在一些实施例中，非人框架区序列包括任何的用于使用如本文所述的一种或多种人CDR序列产生重链和/或轻链可变结构域的序列，包括例如哺乳动物，例如小鼠、大鼠、兔子、猪、牛(例如，牛、公牛、水牛)、鹿、绵羊、山羊、鸡、猫、狗、雪貂、灵长类(例如，小猿，猕猴)等。在一些实施例中，非人抗LIGHT抗体包括将一种或多种本文所述的人CDR序列移植到非人框架区中(例如，鼠或鸡的框架区序列)所产生的抗LIGHT抗体。
示例性人LIGHT的氨基酸序列包含SEQ ID NO：78所示的氨基酸序列或由SEQ ID NO：78所示的氨基酸序列组成。
在一些实施例中，本文所述抗LIGHT抗体特异性识别人LIGHT中的表位。在一些实施例中，所述抗LIGHT抗体与除人之外其它物种的LIGHT发生交叉反应。在一些实施例中，所述抗LIGHT抗体对人LIGHT是完全特异性的，并且不与其它非人物种发生交叉反应。
在一些实施例中，所述抗LIGHT抗体与LIGHT蛋白(或其片段)的至少一种等位基因变体交叉反应。在一些实施例中，等位基因变体与天然存在的LIGHT蛋白(或其片段)相比，具有至多30个(如1、2、3、4、5、6、7、8、9、10、15、20、25或30个)的氨基酸取代(例如保守取 代)。在一些实施例中，所述抗LIGHT抗体不与LIGHT蛋白(或其片段)的任何等位基因变体发生交叉反应。
在一些实施例中，所述抗LIGHT抗体与LIGHT蛋白的至少一种种间变体发生交叉反应。在一些实施例中，例如，LIGHT蛋白(或其片段)是人LIGHT，并且LIGHT蛋白(或其片段)的种间变体是食蟹猴中的变体。在一些实施例中，所述抗LIGHT抗体不与LIGHT蛋白的任何种间变体发生交叉反应。
在一些实施例中，如本文所述的任一抗LIGHT抗体，所述抗LIGHT抗体包含抗体重链恒定区和抗体轻链恒定区。在一些实施例中，所述抗LIGHT抗体包含IgG1型重链恒定区。在一些实施例中，所述抗LIGHT抗体包含IgG2型重链恒定区。在一些实施例中，所述抗LIGHT抗体包含IgG3型重链恒定区。在一些实施例中，所述抗LIGHT抗体包含IgG4型重链恒定区。在一些实施例中，所述重链恒定区包含(包括由…组成或基本上由…组成)氨基酸序列SEQ ID NO:74。在一些实施例中，所述重链恒定区包含(包括由…组成或基本上由…组成)氨基酸序列SEQ ID NO:75。在一些实施例中，所述抗LIGHT抗体包含κ轻链恒定区。在一些实施例中，所述轻链恒定区包含(包括由…组成或基本上由…组成)氨基酸序列SEQ ID NO:76。在一些实施例中，所述抗LIGHT抗体包含λ轻链恒定区。在一些实施例中，所述轻链恒定区包含(包括由…组成或基本上由…组成)氨基酸序列SEQ ID NO:77。在一些实施例中，所述抗LIGHT抗体包含抗体重链可变结构域和抗体轻链可变结构域。
在一些实施例中，所述抗LIGHT抗体，包含重链可变结构域(VH)，所述VH包含：重链互补决定区(HC-CDR)1，其包含GYFIN(SEQ ID NO:1)；HC-CDR2，其包含RIYPYNVX1TFYNQNFKG(SEQ ID NO:45)，其中X1为D或N；和HC-CDR3，其包含GTHYYGSSGAMDY(SEQ ID NO:16)；以及轻链可变结构域(VL)，所述VL包含：轻链互补决定区(LC-CDR)1，其包含KASQNVGTAVA(SEQ ID NO:23)；LC-CDR2，其包含SASNRYT(SEQ ID NO:30)；和LC-CDR3，其包含QQYSSYPYT(SEQ ID NO:37)。
在一些实施例中，所述抗LIGHT抗体包含VH，所述VH包含：HC-CDR1，其包含SEQ ID NO:1所示的氨基酸序列或其变体，所述变体包含至多约3个(例如1、2或3个)氨基酸的取代；HC-CDR2，其包含SEQ ID NOs:8-9中任一所示的氨基酸序列或其变体，所述变体包含至多约3个(例如1、2或3个)氨基酸的取代；和HC-CDR3，其包含SEQ ID NO:16所示的氨基酸序列或其变体，所述变体包含至多约3个(例如1、2或3个)氨基酸的取代。
在一些实施例中，所述抗LIGHT抗体包含VH，所述VH包含：HC-CDR1，其包含SEQ ID NO:1所示的氨基酸序列，HC-CDR2，其包含SEQ ID NOs:8-9中任一所示的氨基酸序列，HC-CDR3，其包含SEQ ID NO:16所示的氨基酸序列。
在一些实施例中，所述抗LIGHT抗体包含VL，所述VL包含：LC-CDR1，其包含SEQ ID NO:23所示的氨基酸序列或其变体，所述变体包含至多约3个(例如1、2或3个)氨基酸的取代；LC-CDR2，其包含SEQ ID NO:30所示的氨基酸序列或其变体，所述变体包含至多约3个(例如 1、2或3个)氨基酸的取代；和LC-CDR3，其包含SEQ ID NO:37所示的氨基酸序列或其变体，所述变体包含至多约3个(例如1、2或3个)氨基酸的取代。
在一些实施例中，所述抗LIGHT抗体包含VL，所述VL包含：LC-CDR1，其包含SEQ ID NO:23所示的氨基酸序列，LC-CDR2，其包含SEQ ID NO:30所示的氨基酸序列，LC-CDR3，其包含SEQ ID NO:37所示的氨基酸序列。
在一些实施例中，所述抗LIGHT抗体包含VH，所述VH包含：HC-CDR1，其包含SEQ ID NO:1所示的氨基酸序列或其变体，所述变体包含至多约3个(例如1、2或3个)氨基酸的取代；HC-CDR2，其包含SEQ ID NOs:8-9中任一所示的氨基酸序列或其变体，所述变体包含至多约3个(例如1、2或3个)氨基酸的取代；和HC-CDR3，其包含SEQ ID NO:16所示的氨基酸序列或其变体，所述变体包含至多约3个(例如1、2或3个)氨基酸的取代；以及VL，所述VL包含：LC-CDR1，其包含SEQ ID NO:23所示的氨基酸序列或其变体，所述变体包含至多约3个(例如1、2或3个)氨基酸的取代；LC-CDR2，其包含SEQ ID NO:30所示的氨基酸序列或其变体，所述变体包含至多约3个(例如1、2或3个)氨基酸的取代；和LC-CDR3，其包含SEQ ID NO:37所示的氨基酸序列或其变体，所述变体包含至多约3个(例如1、2或3个)氨基酸的取代。
在一些实施例中，所述抗LIGHT抗体包含VH，所述VH包含：HC-CDR1，其包含SEQ ID NO:1所示的氨基酸序列，HC-CDR2，其包含SEQ ID NOs:8-9中任一所示的氨基酸序列，和HC-CDR3，其包含SEQ ID NO:16所示的氨基酸序列；以及VL，所述VL包含：LC-CDR1，其包含SEQ ID NO:23所示的氨基酸序列，LC-CDR2，其包含SEQ ID NO:30所示的氨基酸序列，和LC-CDR3，其包含SEQ ID NO:37所示的氨基酸序列。
在一些实施例中，所述抗LIGHT抗体包含VH，所述VH包含：HC-CDR1，其包含氨基酸序列SEQ ID NO:1，HC-CDR2，其包含氨基酸序列SEQ ID NO:8，HC-CDR3，其包含氨基酸序列SEQ ID NO:16，或者所述VH的变体，其HC-CDRs中包含至多约5个氨基酸的取代；以及VL，所述VL包含：LC-CDR1，其包含氨基酸序列SEQ ID NO:23，LC-CDR2，其包含氨基酸序列SEQ ID NO:30，LC-CDR3，其包含氨基酸序列SEQ ID NO:37，或者所述VL的变体，其LC-CDRs中包含至多约5个氨基酸的取代。
在一些实施例中，所述抗LIGHT抗体包含VH，所述VH包含：HC-CDR1，其包含氨基酸序列SEQ ID NO:1，HC-CDR2，其包含氨基酸序列SEQ ID NO:8，和HC-CDR3，其包含氨基酸序列SEQ ID NO:16；以及VL，所述VL包含：LC-CDR1，其包含氨基酸序列SEQ ID NO:23，LC-CDR2，其包含氨基酸序列SEQ ID NO:30，和LC-CDR3，其包含氨基酸序列SEQ ID NO:37。
在一些实施例中，所述抗LIGHT抗体包含VH，所述VH包含：HC-CDR1，其包含氨基酸序列SEQ ID NO:1，HC-CDR2，其包含氨基酸序列SEQ ID NO:9，HC-CDR3，其包含氨基酸序列SEQ ID NO:16，或者所述VH的变体，其HC-CDRs中包含至多约5个氨基酸的取代；以及VL，所述VL包含：LC-CDR1，其包含氨基酸序列SEQ ID NO:23，LC-CDR2，其包含氨基酸序列SEQ ID  NO:30，LC-CDR3，其包含氨基酸序列SEQ ID NO:37，或者所述VL的变体，其LC-CDRs中包含至多约5个氨基酸的取代。
在一些实施例中，所述抗LIGHT抗体包含VH，所述VH包含：HC-CDR1，其包含氨基酸序列SEQ ID NO:1，HC-CDR2，其包含氨基酸序列SEQ ID NO:9，和HC-CDR3，其包含氨基酸序列SEQ ID NO:16；以及VL，所述VL包含：LC-CDR1，其包含氨基酸序列SEQ ID NO:23，LC-CDR2，其包含氨基酸序列SEQ ID NO:30，和LC-CDR3，其包含氨基酸序列SEQ ID NO:37。
在一些实施例中，所述抗LIGHT抗体包含VH，所述VH包含如SEQ ID NOs:46-53中所示的任一氨基酸序列所示的VH包含的HC-CDR1、HC-CDR2和HC-CDR3；以及VL，所述VL包含如SEQ ID NOs:62-65中任一氨基酸序列所示的VL包含的LC-CDR1、LC-CDR2和LC-CDR3。
在一些实施例中，所述抗LIGHT抗体包含VH，其包含如氨基酸序列SEQ ID NO:46所示的VH包含的HC-CDR1、HC-CDR2和HC-CDR3；以及VL，其包含如氨基酸序列SEQ ID NO:62所示的VL包含的LC-CDR1、LC-CDR2和LC-CDR3。
在一些实施例中，所述抗LIGHT抗体包含VH，其包含如氨基酸序列SEQ ID NO:47所示的VH包含的HC-CDR1、HC-CDR2和HC-CDR3；以及VL，其包含如氨基酸序列SEQ ID NO:63所示的VL包含的LC-CDR1、LC-CDR2和LC-CDR3。
在一些实施例中，所述抗LIGHT抗体包含VH，其包含如氨基酸序列SEQ ID NO:48所示的VH包含的HC-CDR1、HC-CDR2和HC-CDR3；以及VL，其包含如氨基酸序列SEQ ID NO:63所示的VL包含的LC-CDR1、LC-CDR2和LC-CDR3。
在一些实施例中，所述抗LIGHT抗体包含VH，其包含如氨基酸序列SEQ ID NO:49所示的VH包含的HC-CDR1、HC-CDR2和HC-CDR3；以及VL，其包含如氨基酸序列SEQ ID NO:63所示的VL包含的LC-CDR1、LC-CDR2和LC-CDR3。
在一些实施例中，所述抗LIGHT抗体包含VH，其包含如氨基酸序列SEQ ID NO:50所示的VH包含的HC-CDR1、HC-CDR2和HC-CDR3；以及VL，其包含如氨基酸序列SEQ ID NO:63所示的VL包含的LC-CDR1、LC-CDR2和LC-CDR3。
在一些实施例中，所述抗LIGHT抗体包含VH，其包含如氨基酸序列SEQ ID NO:47所示的VH包含的HC-CDR1、HC-CDR2和HC-CDR3；以及VL，其包含如氨基酸序列SEQ ID NO:64所示的VL包含的LC-CDR1、LC-CDR2和LC-CDR3。
在一些实施例中，所述抗LIGHT抗体包含VH，其包含如氨基酸序列SEQ ID NO:48所示的VH包含的HC-CDR1、HC-CDR2和HC-CDR3；以及VL，其包含如氨基酸序列SEQ ID NO:64所示的VL包含的LC-CDR1、LC-CDR2和LC-CDR3。
在一些实施例中，所述抗LIGHT抗体包含VH，其包含如氨基酸序列SEQ ID NO:49所示的VH包含的HC-CDR1、HC-CDR2和HC-CDR3；以及VL，其包含如氨基酸序列SEQ ID NO:64所示的VL包含的LC-CDR1、LC-CDR2和LC-CDR3。
在一些实施例中，所述抗LIGHT抗体包含VH，其包含如氨基酸序列SEQ ID NO:50所示的VH包含的HC-CDR1、HC-CDR2和HC-CDR3；以及VL，其包含如氨基酸序列SEQ ID NO:64所示的VL包含的LC-CDR1、LC-CDR2和LC-CDR3。
在一些实施例中，所述抗LIGHT抗体包含VH，其包含如氨基酸序列SEQ ID NO:47所示的VH包含的HC-CDR1、HC-CDR2和HC-CDR3；以及VL，其包含如氨基酸序列SEQ ID NO:65所示的VL包含的LC-CDR1、LC-CDR2和LC-CDR3。
在一些实施例中，所述抗LIGHT抗体包含VH，其包含如氨基酸序列SEQ ID NO:48所示的VH包含的HC-CDR1、HC-CDR2和HC-CDR3；以及VL，其包含如氨基酸序列SEQ ID NO:65所示的VL包含的LC-CDR1、LC-CDR2和LC-CDR3。
在一些实施例中，所述抗LIGHT抗体包含VH，其包含如氨基酸序列SEQ ID NO:49所示的VH包含的HC-CDR1、HC-CDR2和HC-CDR3；以及VL，其包含如氨基酸序列SEQ ID NO:65所示的VL包含的LC-CDR1、LC-CDR2和LC-CDR3。
在一些实施例中，所述抗LIGHT抗体包含VH，其包含如氨基酸序列SEQ ID NO:50所示的VH包含的HC-CDR1、HC-CDR2和HC-CDR3；以及VL，其包含如氨基酸序列SEQ ID NO:65所示的VL包含的LC-CDR1、LC-CDR2和LC-CDR3。
在一些实施例中，所述抗LIGHT抗体包含VH，其包含如氨基酸序列SEQ ID NO:51所示的VH包含的HC-CDR1、HC-CDR2和HC-CDR3；以及VL，其包含如氨基酸序列SEQ ID NO:63所示的VL包含的LC-CDR1、LC-CDR2和LC-CDR3。
在一些实施例中，所述抗LIGHT抗体包含VH，其包含如氨基酸序列SEQ ID NO:52所示的VH包含的HC-CDR1、HC-CDR2和HC-CDR3；以及VL，其包含如氨基酸序列SEQ ID NO:65所示的VL包含的LC-CDR1、LC-CDR2和LC-CDR3。
在一些实施例中，所述抗LIGHT抗体包含VH，其包含如氨基酸序列SEQ ID NO:53所示的VH包含的HC-CDR1、HC-CDR2和HC-CDR3；以及VL，其包含如氨基酸序列SEQ ID NO:65所示的VL包含的LC-CDR1、LC-CDR2和LC-CDR3。
在一些实施例中，所述抗LIGHT抗体包含VH，其包含如氨基酸序列SEQ ID NO:51所示的VH包含的HC-CDR1、HC-CDR2和HC-CDR3；以及VL，其包含如氨基酸序列SEQ ID NO:65所示的VL包含的LC-CDR1、LC-CDR2和LC-CDR3。
在一些实施例中，所述抗LIGHT抗体包含：VH，所述VH包含SEQ ID NOs:46-53中任一所示的氨基酸序列或其变体，所述变体与SEQ ID NOs:46-53中任一所示的氨基酸序列具有至少约80％(例如至少80％、85％、90％、95％、96％、97％、98％或99％)序列同一性；以及VL，所述VL包含SEQ ID NOs:62-65中任一所示的氨基酸序列或其变体，所述变体与SEQ ID NOs:62-65中任一所示的氨基酸序列具有至少约80％(例如至少80％、85％、90％、95％、96％、97％、98％或99％)序列同一性。在一些实施例中，所述抗LIGHT抗体包含VH，所述VH包含SEQ ID NOs:46- 53中任一所示的氨基酸序列，以及VL，所述VL包含SEQ ID NOs:62-65中任一所示的氨基酸序列。
在一些实施例中，所述抗LIGHT抗体包含：VH，所述VH包含氨基酸序列SEQ ID NO:46或其变体，所述变体与氨基酸序列SEQ ID NO:46具有至少约80％(例如至少80％、85％、90％、95％、96％、97％、98％或99％)序列同一性；以及VL，所述VL包含氨基酸序列SEQ ID NO:62或其变体，所述变体与氨基酸序列SEQ ID NO:62具有至少约80％(例如至少80％、85％、90％、95％、96％、97％、98％或99％)序列同一性。在一些实施例中，所述抗LIGHT抗体包含VH，所述VH包含氨基酸序列SEQ ID NO:46，以及VL，所述VL包含氨基酸序列SEQ ID NO:62。
在一些实施例中，所述抗LIGHT抗体包含：VH，所述VH包含氨基酸序列SEQ ID NO:47或其变体，所述变体与氨基酸序列SEQ ID NO:47具有至少约80％(例如至少80％、85％、90％、95％、96％、97％、98％或99％)序列同一性；以及VL，所述VL包含氨基酸序列SEQ ID NO:63或其变体，所述变体与氨基酸序列SEQ ID NO:63具有至少约80％(例如至少80％、85％、90％、95％、96％、97％、98％或99％)序列同一性。在一些实施例中，所述抗LIGHT抗体包含VH，所述VH包含氨基酸序列SEQ ID NO:47，以及VL，所述VL包含氨基酸序列SEQ ID NO:63。
在一些实施例中，所述抗LIGHT抗体包含：VH，所述VH包含氨基酸序列SEQ ID NO:48或其变体，所述变体与氨基酸序列SEQ ID NO:48具有至少约80％(例如至少80％、85％、90％、95％、96％、97％、98％或99％)序列同一性；以及VL，所述VL包含氨基酸序列SEQ ID NO:63或其变体，所述变体与氨基酸序列SEQ ID NO:63具有至少约80％(例如至少80％、85％、90％、95％、96％、97％、98％或99％)序列同一性。在一些实施例中，所述抗LIGHT抗体包含VH，所述VH包含氨基酸序列SEQ ID NO:48，以及VL，所述VL包含氨基酸序列SEQ ID NO:63。
在一些实施例中，所述抗LIGHT抗体包含：VH，所述VH包含氨基酸序列SEQ ID NO:49或其变体，所述变体与氨基酸序列SEQ ID NO:49具有至少约80％(例如至少80％、85％、90％、95％、96％、97％、98％或99％)序列同一性；以及VL，所述VL包含氨基酸序列SEQ ID NO:63或其变体，所述变体与氨基酸序列SEQ ID NO:63具有至少约80％(例如至少80％、85％、90％、95％、96％、97％、98％或99％)序列同一性。在一些实施例中，所述抗LIGHT抗体包含VH，所述VH包含氨基酸序列SEQ ID NO:49，以及VL，所述VL包含氨基酸序列SEQ ID NO:63。
在一些实施例中，所述抗LIGHT抗体包含：VH，所述VH包含氨基酸序列SEQ ID NO:50或其变体，所述变体与氨基酸序列SEQ ID NO:50具有至少约80％(例如至少80％、85％、90％、95％、96％、97％、98％或99％)序列同一性；以及VL，所述VL包含氨基酸序列SEQ ID NO:63或其变体，所述变体与氨基酸序列SEQ ID NO:63具有至少约80％(例如至少80％、85％、90％、95％、96％、97％、98％或99％)序列同一性。在一些实施例中，所述抗LIGHT抗体包含VH，所述VH包含氨基酸序列SEQ ID NO:50，以及VL，所述VL包含氨基酸序列SEQ ID NO:63。
在一些实施例中，所述抗LIGHT抗体包含：VH，所述VH包含氨基酸序列SEQ ID NO:47或其变体，所述变体与氨基酸序列SEQ ID NO:47具有至少约80％(例如至少80％、85％、90％、 95％、96％、97％、98％或99％)序列同一性；以及VL，所述VL包含氨基酸序列SEQ ID NO:64或其变体，所述变体与氨基酸序列SEQ ID NO:64具有至少约80％(例如至少80％、85％、90％、95％、96％、97％、98％或99％)序列同一性。在一些实施例中，所述抗LIGHT抗体包含VH，所述VH包含氨基酸序列SEQ ID NO:47，以及VL，所述VL包含氨基酸序列SEQ ID NO:64。
在一些实施例中，所述抗LIGHT抗体包含：VH，所述VH包含氨基酸序列SEQ ID NO:48或其变体，所述变体与氨基酸序列SEQ ID NO:48具有至少约80％(例如至少80％、85％、90％、95％、96％、97％、98％或99％)序列同一性；以及VL，所述VL包含氨基酸序列SEQ ID NO:64或其变体，所述变体与氨基酸序列SEQ ID NO:64具有至少约80％(例如至少80％、85％、90％、95％、96％、97％、98％或99％)序列同一性。在一些实施例中，所述抗LIGHT抗体包含VH，所述VH包含氨基酸序列SEQ ID NO:48，以及VL，所述VL包含氨基酸序列SEQ ID NO:64。
在一些实施例中，所述抗LIGHT抗体包含：VH，所述VH包含氨基酸序列SEQ ID NO:49或其变体，所述变体与氨基酸序列SEQ ID NO:49具有至少约80％(例如至少80％、85％、90％、95％、96％、97％、98％或99％)序列同一性；以及VL，所述VL包含氨基酸序列SEQ ID NO:64或其变体，所述变体与氨基酸序列SEQ ID NO:64具有至少约80％(例如至少80％、85％、90％、95％、96％、97％、98％或99％)序列同一性。在一些实施例中，所述抗LIGHT抗体包含VH，所述VH包含氨基酸序列SEQ ID NO:49，以及VL，所述VL包含氨基酸序列SEQ ID NO:64。
在一些实施例中，所述抗LIGHT抗体包含：VH，所述VH包含氨基酸序列SEQ ID NO:50或其变体，所述变体与氨基酸序列SEQ ID NO:50具有至少约80％(例如至少80％、85％、90％、95％、96％、97％、98％或99％)序列同一性；以及VL，所述VL包含氨基酸序列SEQ ID NO:64或其变体，所述变体与氨基酸序列SEQ ID NO:64具有至少约80％(例如至少80％、85％、90％、95％、96％、97％、98％或99％)序列同一性。在一些实施例中，所述抗LIGHT抗体包含VH，所述VH包含氨基酸序列SEQ ID NO:50，以及VL，所述VL包含氨基酸序列SEQ ID NO:64。
在一些实施例中，所述抗LIGHT抗体包含：VH，所述VH包含氨基酸序列SEQ ID NO:47或其变体，所述变体与氨基酸序列SEQ ID NO:47具有至少约80％(例如至少80％、85％、90％、95％、96％、97％、98％或99％)序列同一性；以及VL，所述VL包含氨基酸序列SEQ ID NO:65或其变体，所述变体与氨基酸序列SEQ ID NO:65具有至少约80％(例如至少80％、85％、90％、95％、96％、97％、98％或99％)序列同一性。在一些实施例中，所述抗LIGHT抗体包含VH，所述VH包含氨基酸序列SEQ ID NO:47，以及VL，所述VL包含氨基酸序列SEQ ID NO:65。
在一些实施例中，所述抗LIGHT抗体包含：VH，所述VH包含氨基酸序列SEQ ID NO:48或其变体，所述变体与氨基酸序列SEQ ID NO:48具有至少约80％(例如至少80％、85％、90％、95％、96％、97％、98％或99％)序列同一性；以及VL，所述VL包含氨基酸序列SEQ ID NO:65或其变体，所述变体与氨基酸序列SEQ ID NO:65具有至少约80％(例如至少80％、85％、90％、95％、96％、97％、98％或99％)序列同一性。在一些实施例中，所述抗LIGHT抗体包含VH，所述VH包含氨基酸序列SEQ ID NO:48，以及VL，所述VL包含氨基酸序列SEQ ID NO:65。
在一些实施例中，所述抗LIGHT抗体包含：VH，所述VH包含氨基酸序列SEQ ID NO:49或其变体，所述变体与氨基酸序列SEQ ID NO:49具有至少约80％(例如至少80％、85％、90％、95％、96％、97％、98％或99％)序列同一性；以及VL，所述VL包含氨基酸序列SEQ ID NO:65或其变体，所述变体与氨基酸序列SEQ ID NO:65具有至少约80％(例如至少80％、85％、90％、95％、96％、97％、98％或99％)序列同一性。在一些实施例中，所述抗LIGHT抗体包含VH，所述VH包含氨基酸序列SEQ ID NO:49，以及VL，所述VL包含氨基酸序列SEQ ID NO:65。
在一些实施例中，所述抗LIGHT抗体包含：VH，所述VH包含氨基酸序列SEQ ID NO:50或其变体，所述变体与氨基酸序列SEQ ID NO:50具有至少约80％(例如至少80％、85％、90％、95％、96％、97％、98％或99％)序列同一性；以及VL，所述VL包含氨基酸序列SEQ ID NO:65或其变体，所述变体与氨基酸序列SEQ ID NO:65具有至少约80％(例如至少80％、85％、90％、95％、96％、97％、98％或99％)序列同一性。在一些实施例中，所述抗LIGHT抗体包含VH，所述VH包含氨基酸序列SEQ ID NO:50，以及VL，所述VL包含氨基酸序列SEQ ID NO:65。
在一些实施例中，所述抗LIGHT抗体包含：VH，所述VH包含氨基酸序列SEQ ID NO:51或其变体，所述变体与氨基酸序列SEQ ID NO:51具有至少约80％(例如至少80％、85％、90％、95％、96％、97％、98％或99％)序列同一性；以及VL，所述VL包含氨基酸序列SEQ ID NO:63或其变体，所述变体与氨基酸序列SEQ ID NO:63具有至少约80％(例如至少80％、85％、90％、95％、96％、97％、98％或99％)序列同一性。在一些实施例中，所述抗LIGHT抗体包含VH，所述VH包含氨基酸序列SEQ ID NO:51，以及VL，所述VL包含氨基酸序列SEQ ID NO:63。
在一些实施例中，所述抗LIGHT抗体包含：VH，所述VH包含氨基酸序列SEQ ID NO:52或其变体，所述变体与氨基酸序列SEQ ID NO:52具有至少约80％(例如至少80％、85％、90％、95％、96％、97％、98％或99％)序列同一性；以及VL，所述VL包含氨基酸序列SEQ ID NO:65或其变体，所述变体与氨基酸序列SEQ ID NO:65具有至少约80％(例如至少80％、85％、90％、95％、96％、97％、98％或99％)序列同一性。在一些实施例中，所述抗LIGHT抗体包含VH，所述VH包含氨基酸序列SEQ ID NO:52，以及VL，所述VL包含氨基酸序列SEQ ID NO:65。
在一些实施例中，所述抗LIGHT抗体包含：VH，所述VH包含氨基酸序列SEQ ID NO:53或其变体，所述变体与氨基酸序列SEQ ID NO:53具有至少约80％(例如至少80％、85％、90％、95％、96％、97％、98％或99％)序列同一性；以及VL，所述VL包含氨基酸序列SEQ ID NO:65或其变体，所述变体与氨基酸序列SEQ ID NO:65具有至少约80％(例如至少80％、85％、90％、95％、96％、97％、98％或99％)序列同一性。在一些实施例中，所述抗LIGHT抗体包含VH，所述VH包含氨基酸序列SEQ ID NO:53，以及VL，所述VL包含氨基酸序列SEQ ID NO:65。
在一些实施例中，所述抗LIGHT抗体包含：VH，所述VH包含氨基酸序列SEQ ID NO:51或其变体，所述变体与氨基酸序列SEQ ID NO:51具有至少约80％(例如至少80％、85％、90％、95％、96％、97％、98％或99％)序列同一性；以及VL，所述VL包含氨基酸序列SEQ ID NO:65或其变体，所述变体与氨基酸序列SEQ ID NO:65具有至少约80％(例如至少80％、85％、90％、 95％、96％、97％、98％或99％)序列同一性。在一些实施例中，所述抗LIGHT抗体包含VH，所述VH包含氨基酸序列SEQ ID NO:51，以及VL，所述VL包含氨基酸序列SEQ ID NO:65。
在一些实施例中，所述抗LIGHT抗体包含VH，所述VH包含：HC-CDR1，其包含氨基酸序列SEQ ID NO:2，HC-CDR2，其包含氨基酸序列SEQ ID NO:10，HC-CDR3，其包含氨基酸序列SEQ ID NO:17，或者所述VH的变体，其HC-CDRs中包含至多约5个氨基酸的取代；以及VL，所述VL包含：LC-CDR1，其包含氨基酸序列SEQ ID NO:24，LC-CDR2，其包含氨基酸序列SEQ ID NO:31，LC-CDR3，其包含氨基酸序列SEQ ID NO:38，或者所述VL的变体，其LC-CDRs中包含至多约5个氨基酸的取代。
在一些实施例中，所述抗LIGHT抗体包含VH，所述VH包含：HC-CDR1，其包含氨基酸序列SEQ ID NO:2，HC-CDR2，其包含氨基酸序列SEQ ID NO:10，和HC-CDR3，其包含氨基酸序列SEQ ID NO:17；以及VL，所述VL包含：LC-CDR1，其包含氨基酸序列SEQ ID NO:24，LC-CDR2，其包含氨基酸序列SEQ ID NO:31，和LC-CDR3，其包含氨基酸序列SEQ ID NO:38。
在一些实施例中，所述抗LIGHT抗体包含VH，其包含如氨基酸序列SEQ ID NO:54所示的VH包含的HC-CDR1、HC-CDR2和HC-CDR3；以及VL，其包含如氨基酸序列SEQ ID NO:66所示的VL包含的LC-CDR1、LC-CDR2和LC-CDR3。
在一些实施例中，所述抗LIGHT抗体包含：VH，所述VH包含氨基酸序列SEQ ID NO:54或其变体，所述变体与氨基酸序列SEQ ID NO:54具有至少约80％(例如至少80％、85％、90％、95％、96％、97％、98％或99％)序列同一性；以及VL，所述VL包含氨基酸序列SEQ ID NO:66或其变体，所述变体与氨基酸序列SEQ ID NO:66具有至少约80％(例如至少80％、85％、90％、95％、96％、97％、98％或99％)序列同一性。在一些实施例中，所述抗LIGHT抗体包含VH，所述VH包含氨基酸序列SEQ ID NO:54，以及VL，所述VL包含氨基酸序列SEQ ID NO:66。
在一些实施例中，所述抗LIGHT抗体包含VH，所述VH包含：HC-CDR1，其包含氨基酸序列SEQ ID NO:2，HC-CDR2，其包含氨基酸序列SEQ ID NO:10，HC-CDR3，其包含氨基酸序列SEQ ID NO:17，或者所述VH的变体，其HC-CDRs中包含至多约5个氨基酸的取代；以及VL，所述VL包含：LC-CDR1，其包含氨基酸序列SEQ ID NO:25，LC-CDR2，其包含氨基酸序列SEQ ID NO:31，LC-CDR3，其包含氨基酸序列SEQ ID NO:39，或者所述VL的变体，其LC-CDRs中包含至多约5个氨基酸的取代。
在一些实施例中，所述抗LIGHT抗体包含VH，所述VH包含：HC-CDR1，其包含氨基酸序列SEQ ID NO:2，HC-CDR2，其包含氨基酸序列SEQ ID NO:10，和HC-CDR3，其包含氨基酸序列SEQ ID NO:17；以及VL，所述VL包含：LC-CDR1，其包含氨基酸序列SEQ ID NO:25，LC-CDR2，其包含氨基酸序列SEQ ID NO:31，和LC-CDR3，其包含氨基酸序列SEQ ID NO:39。
在一些实施例中，所述抗LIGHT抗体包含VH，其包含如氨基酸序列SEQ ID NO:55所示的VH包含的HC-CDR1、HC-CDR2和HC-CDR3；以及VL，其包含如氨基酸序列SEQ ID NO:67所示的VL包含的LC-CDR1、LC-CDR2和LC-CDR3。
在一些实施例中，所述抗LIGHT抗体包含：VH，所述VH包含氨基酸序列SEQ ID NO:55或其变体，所述变体与氨基酸序列SEQ ID NO:55具有至少约80％(例如至少80％、85％、90％、95％、96％、97％、98％或99％)序列同一性；以及VL，所述VL包含氨基酸序列SEQ ID NO:67或其变体，所述变体与氨基酸序列SEQ ID NO:67具有至少约80％(例如至少80％、85％、90％、95％、96％、97％、98％或99％)序列同一性。在一些实施例中，所述抗LIGHT抗体包含VH，所述VH包含氨基酸序列SEQ ID NO:55，以及VL，所述VL包含氨基酸序列SEQ ID NO:67。
在一些实施例中，所述抗LIGHT抗体包含VH，所述VH包含：HC-CDR1，其包含氨基酸序列SEQ ID NO:3，HC-CDR2，其包含氨基酸序列SEQ ID NO:11，HC-CDR3，其包含氨基酸序列SEQ ID NO:18，或者所述VH的变体，其HC-CDRs中包含至多约5个氨基酸的取代；以及VL，所述VL包含：LC-CDR1，其包含氨基酸序列SEQ ID NO:26，LC-CDR2，其包含氨基酸序列SEQ ID NO:32，LC-CDR3，其包含氨基酸序列SEQ ID NO:40，或者所述VL的变体，其LC-CDRs中包含至多约5个氨基酸的取代。
在一些实施例中，所述抗LIGHT抗体包含VH，所述VH包含：HC-CDR1，其包含氨基酸序列SEQ ID NO:3，HC-CDR2，其包含氨基酸序列SEQ ID NO:11，和HC-CDR3，其包含氨基酸序列SEQ ID NO:18；以及VL，所述VL包含：LC-CDR1，其包含氨基酸序列SEQ ID NO:26，LC-CDR2，其包含氨基酸序列SEQ ID NO:32，和LC-CDR3，其包含氨基酸序列SEQ ID NO:40。
在一些实施例中，所述抗LIGHT抗体包含VH，其包含如氨基酸序列SEQ ID NO:56所示的VH包含的HC-CDR1、HC-CDR2和HC-CDR3；以及VL，其包含如氨基酸序列SEQ ID NO:68所示的VL包含的LC-CDR1、LC-CDR2和LC-CDR3。
在一些实施例中，所述抗LIGHT抗体包含：VH，所述VH包含氨基酸序列SEQ ID NO:56或其变体，所述变体与氨基酸序列SEQ ID NO:56具有至少约80％(例如至少80％、85％、90％、95％、96％、97％、98％或99％)序列同一性；以及VL，所述VL包含氨基酸序列SEQ ID NO:68或其变体，所述变体与氨基酸序列SEQ ID NO:68具有至少约80％(例如至少80％、85％、90％、95％、96％、97％、98％或99％)序列同一性。在一些实施例中，所述抗LIGHT抗体包含VH，所述VH包含氨基酸序列SEQ ID NO:56，以及VL，所述VL包含氨基酸序列SEQ ID NO:68。
在一些实施例中，所述抗LIGHT抗体包含VH，所述VH包含：HC-CDR1，其包含氨基酸序列SEQ ID NO:3，HC-CDR2，其包含氨基酸序列SEQ ID NO:11，HC-CDR3，其包含氨基酸序列SEQ ID NO:18，或者所述VH的变体，其HC-CDRs中包含至多约5个氨基酸的取代；以及VL，所述VL包含：LC-CDR1，其包含氨基酸序列SEQ ID NO:26，LC-CDR2，其包含氨基酸序列SEQ ID NO:32，LC-CDR3，其包含氨基酸序列SEQ ID NO:41，或者所述VL的变体，其LC-CDRs中包含至多约5个氨基酸的取代。
在一些实施例中，所述抗LIGHT抗体包含VH，所述VH包含：HC-CDR1，其包含氨基酸序列SEQ ID NO:3，HC-CDR2，其包含氨基酸序列SEQ ID NO:11，和HC-CDR3，其包含氨基酸序列 SEQ ID NO:18；以及VL，所述VL包含：LC-CDR1，其包含氨基酸序列SEQ ID NO:26，LC-CDR2，其包含氨基酸序列SEQ ID NO:32，和LC-CDR3，其包含氨基酸序列SEQ ID NO:41。
在一些实施例中，所述抗LIGHT抗体包含VH，其包含如氨基酸序列SEQ ID NO:57所示的VH包含的HC-CDR1、HC-CDR2和HC-CDR3；以及VL，其包含如氨基酸序列SEQ ID NO:69所示的VL包含的LC-CDR1、LC-CDR2和LC-CDR3。
在一些实施例中，所述抗LIGHT抗体包含：VH，所述VH包含氨基酸序列SEQ ID NO:57或其变体，所述变体与氨基酸序列SEQ ID NO:57具有至少约80％(例如至少80％、85％、90％、95％、96％、97％、98％或99％)序列同一性；以及VL，所述VL包含氨基酸序列SEQ ID NO:69或其变体，所述变体与氨基酸序列SEQ ID NO:69具有至少约80％(例如至少80％、85％、90％、95％、96％、97％、98％或99％)序列同一性。在一些实施例中，所述抗LIGHT抗体包含VH，所述VH包含氨基酸序列SEQ ID NO:57，以及VL，所述VL包含氨基酸序列SEQ ID NO:69。
在一些实施例中，所述抗LIGHT抗体包含VH，所述VH包含：HC-CDR1，其包含氨基酸序列SEQ ID NO:4，HC-CDR2，其包含氨基酸序列SEQ ID NO:12，HC-CDR3，其包含氨基酸序列SEQ ID NO:19，或者所述VH的变体，其HC-CDRs中包含至多约5个氨基酸的取代；以及VL，所述VL包含：LC-CDR1，其包含氨基酸序列SEQ ID NO:27，LC-CDR2，其包含氨基酸序列SEQ ID NO:33，LC-CDR3，其包含氨基酸序列SEQ ID NO:42，或者所述VL的变体，其LC-CDRs中包含至多约5个氨基酸的取代。
在一些实施例中，所述抗LIGHT抗体包含VH，所述VH包含：HC-CDR1，其包含氨基酸序列SEQ ID NO:4，HC-CDR2，其包含氨基酸序列SEQ ID NO:12，和HC-CDR3，其包含氨基酸序列SEQ ID NO:19；以及VL，所述VL包含：LC-CDR1，其包含氨基酸序列SEQ ID NO:27，LC-CDR2，其包含氨基酸序列SEQ ID NO:33，和LC-CDR3，其包含氨基酸序列SEQ ID NO:42。
在一些实施例中，所述抗LIGHT抗体包含VH，其包含如氨基酸序列SEQ ID NO:58所示的VH包含的HC-CDR1、HC-CDR2和HC-CDR3；以及VL，其包含如氨基酸序列SEQ ID NO:70所示的VL包含的LC-CDR1、LC-CDR2和LC-CDR3。
在一些实施例中，所述抗LIGHT抗体包含：VH，所述VH包含氨基酸序列SEQ ID NO:58或其变体，所述变体与氨基酸序列SEQ ID NO:58具有至少约80％(例如至少80％、85％、90％、95％、96％、97％、98％或99％)序列同一性；以及VL，所述VL包含氨基酸序列SEQ ID NO:70或其变体，所述变体与氨基酸序列SEQ ID NO:70具有至少约80％(例如至少80％、85％、90％、95％、96％、97％、98％或99％)序列同一性。在一些实施例中，所述抗LIGHT抗体包含VH，所述VH包含氨基酸序列SEQ ID NO:58，以及VL，所述VL包含氨基酸序列SEQ ID NO:70。
在一些实施例中，所述抗LIGHT抗体包含VH，所述VH包含：HC-CDR1，其包含氨基酸序列SEQ ID NO:5，HC-CDR2，其包含氨基酸序列SEQ ID NO:13，HC-CDR3，其包含氨基酸序列SEQ ID NO:20，或者所述VH的变体，其HC-CDRs中包含至多约5个氨基酸的取代；以及VL，所述VL包含：LC-CDR1，其包含氨基酸序列SEQ ID NO:28，LC-CDR2，其包含氨基酸序列SEQ ID  NO:34，LC-CDR3，其包含氨基酸序列SEQ ID NO:43，或者所述VL的变体，其LC-CDRs中包含至多约5个氨基酸的取代。
在一些实施例中，所述抗LIGHT抗体包含VH，所述VH包含：HC-CDR1，其包含氨基酸序列SEQ ID NO:5，HC-CDR2，其包含氨基酸序列SEQ ID NO:13，和HC-CDR3，其包含氨基酸序列SEQ ID NO:20；以及VL，所述VL包含：LC-CDR1，其包含氨基酸序列SEQ ID NO:28，LC-CDR2，其包含氨基酸序列SEQ ID NO:34，和LC-CDR3，其包含氨基酸序列SEQ ID NO:43。
在一些实施例中，所述抗LIGHT抗体包含VH，其包含如氨基酸序列SEQ ID NO:59所示的VH包含的HC-CDR1、HC-CDR2和HC-CDR3；以及VL，其包含如氨基酸序列SEQ ID NO:71所示的VL包含的LC-CDR1、LC-CDR2和LC-CDR3。
在一些实施例中，所述抗LIGHT抗体包含：VH，所述VH包含氨基酸序列SEQ ID NO:59或其变体，所述变体与氨基酸序列SEQ ID NO:59具有至少约80％(例如至少80％、85％、90％、95％、96％、97％、98％或99％)序列同一性；以及VL，所述VL包含氨基酸序列SEQ ID NO:71或其变体，所述变体与氨基酸序列SEQ ID NO:71具有至少约80％(例如至少80％、85％、90％、95％、96％、97％、98％或99％)序列同一性。在一些实施例中，所述抗LIGHT抗体包含VH，所述VH包含氨基酸序列SEQ ID NO:59，以及VL，所述VL包含氨基酸序列SEQ ID NO:71。
在一些实施例中，提供一种分离的抗LIGHT抗体，包含重链可变结构域(VH)，所述VH包含重链互补决定区(HC-CDR)1，其包含DHIMN(SEQ ID NO:6)；HC-CDR2，其包含RIYPVSGETNYNQKFMG(SEQ ID NO:14)；和HC-CDR3，其包含GSYYWNAMDY(SEQ ID NO:21)；以及轻链可变结构域(VL)，所述VL包含：轻链互补决定区(LC-CDR)1，其包含KASQSVDFDGDSYMN(SEQ ID NO:29)或KASQSVDFDGESYMN(SEQ ID NO:83)；LC-CDR2，其包含SASNLES(SEQ ID NO:35)；和LC-CDR3，其包含QQSIEDPWT(SEQ ID NO:43)。
在一些实施例中，所述抗LIGHT抗体包含VH，所述VH包含：HC-CDR1，其包含SEQ ID NO:6所示的氨基酸序列或其变体，所述变体包含至多约3个(例如1、2或3个)氨基酸的取代；HC-CDR2，其包含SEQ ID NO:14所示的氨基酸序列或其变体，所述变体包含至多约3个(例如1、2或3个)氨基酸的取代；和HC-CDR3，其包含SEQ ID NO:21所示的氨基酸序列或其变体，所述变体包含至多约3个(例如1、2或3个)氨基酸的取代。
在一些实施例中，所述抗LIGHT抗体包含VH，所述VH包含：HC-CDR1，其包含SEQ ID NO:6所示的氨基酸序列，HC-CDR2，其包含SEQ ID NO:14所示的氨基酸序列，HC-CDR3，其包含SEQ ID NO:21所示的氨基酸序列。
1.在一些实施例中，所述抗LIGHT抗体包含VL，所述VL包含：LC-CDR1，其包含SEQ ID NOs:29或83中任一所示的氨基酸序列或其变体，所述变体包含至多约3个(例如1、2或3个)氨基酸的取代；LC-CDR2，其包含SEQ ID NO:35所示的氨基酸序列或其变体，所述变体包含至 多约3个(例如1、2或3个)氨基酸的取代；和LC-CDR3，其包含SEQ ID NO:43所示的氨基酸序列或其变体，所述变体包含至多约3个(例如1、2或3个)氨基酸的取代。
在一些实施例中，所述抗LIGHT抗体包含VL，所述VL包含：LC-CDR1，其包含SEQ ID NOs:29或83中任一所示的氨基酸序列，LC-CDR2，其包含SEQ ID NO:35所示的氨基酸序列，LC-CDR3，其包含SEQ ID NO:43所示的氨基酸序列。
在一些实施例中，所述抗LIGHT抗体包含VH，所述VH包含：HC-CDR1，其包含SEQ ID NO:6所示的氨基酸序列或其变体，所述变体包含至多约3个(例如1、2或3个)氨基酸的取代；HC-CDR2，其包含SEQ ID NO:14所示的氨基酸序列或其变体，所述变体包含至多约3个(例如1、2或3个)氨基酸的取代；和HC-CDR3，其包含SEQ ID NO:21所示的氨基酸序列或其变体，所述变体包含至多约3个(例如1、2或3个)氨基酸的取代；以及VL，所述VL包含：LC-CDR1，其包含SEQ ID NOs:29或83中任一所示的氨基酸序列或其变体，所述变体包含至多约3个(例如1、2或3个)氨基酸的取代；LC-CDR2，其包含SEQ ID NO:35所示的氨基酸序列或其变体，所述变体包含至多约3个(例如1、2或3个)氨基酸的取代；和LC-CDR3，其包含SEQ ID NO:43所示的氨基酸序列或其变体，所述变体包含至多约3个(例如1、2或3个)氨基酸的取代。
在一些实施例中，所述抗LIGHT抗体包含VH，所述VH包含：HC-CDR1，其包含SEQ ID NO:6所示的氨基酸序列，HC-CDR2，其包含SEQ ID NO:14所示的氨基酸序列，和HC-CDR3，其包含SEQ ID NO:21所示的氨基酸序列；以及VL，所述VL包含：LC-CDR1，其包含SEQ ID NOs:29或83中任一所示的氨基酸序列，LC-CDR2，其包含SEQ ID NO:35所示的氨基酸序列，和LC-CDR3，其包含SEQ ID NO:43所示的氨基酸序列。
在一些实施例中，所述抗LIGHT抗体包含VH，所述VH包含：HC-CDR1，其包含氨基酸序列SEQ ID NO:6，HC-CDR2，其包含氨基酸序列SEQ ID NO:14，HC-CDR3，其包含氨基酸序列SEQ ID NO:21，或者所述VH的变体，其HC-CDRs中包含至多约5个氨基酸的取代；以及VL，所述VL包含：LC-CDR1，其包含氨基酸序列SEQ ID NO:29，LC-CDR2，其包含氨基酸序列SEQ ID NO:35，LC-CDR3，其包含氨基酸序列SEQ ID NO:43，或者所述VL的变体，其LC-CDRs中包含至多约5个氨基酸的取代。
在一些实施例中，所述抗LIGHT抗体包含VH，所述VH包含：HC-CDR1，其包含氨基酸序列SEQ ID NO:6，HC-CDR2，其包含氨基酸序列SEQ ID NO:14，和HC-CDR3，其包含氨基酸序列SEQ ID NO:21；以及VL，所述VL包含：LC-CDR1，其包含氨基酸序列SEQ ID NO:29，LC-CDR2，其包含氨基酸序列SEQ ID NO:35，和LC-CDR3，其包含氨基酸序列SEQ ID NO:43。
在一些实施例中，所述抗LIGHT抗体包含VH，所述VH包含：HC-CDR1，其包含氨基酸序列SEQ ID NO:6，HC-CDR2，其包含氨基酸序列SEQ ID NO:14，HC-CDR3，其包含氨基酸序列SEQ ID NO:21，或者所述VH的变体，其HC-CDRs中包含至多约5个氨基酸的取代；以及VL，所述VL包含：LC-CDR1，其包含氨基酸序列SEQ ID NO:83，LC-CDR2，其包含氨基酸序列SEQ ID  NO:35，LC-CDR3，其包含氨基酸序列SEQ ID NO:43，或者所述VL的变体，其LC-CDRs中包含至多约5个氨基酸的取代。
在一些实施例中，所述抗LIGHT抗体包含VH，所述VH包含：HC-CDR1，其包含氨基酸序列SEQ ID NO:6，HC-CDR2，其包含氨基酸序列SEQ ID NO:14，和HC-CDR3，其包含氨基酸序列SEQ ID NO:21；以及VL，所述VL包含：LC-CDR1，其包含氨基酸序列SEQ ID NO:83，LC-CDR2，其包含氨基酸序列SEQ ID NO:35，和LC-CDR3，其包含氨基酸序列SEQ ID NO:43。
在一些实施例中，所述抗LIGHT抗体包含：VH，所述VH包含如SEQ ID NOs:60，84-85中任一氨基酸序列所示的VH包含的HC-CDR1、HC-CDR2和HC-CDR3，以及VL，所述VL包含如SEQ ID NOs:72，86-91中任一氨基酸序列所示的VL包含的LC-CDR1、LC-CDR2和LC-CDR3。
在一些实施例中，所述抗LIGHT抗体包含VH，其包含如氨基酸序列SEQ ID NO:60所示的VH包含的HC-CDR1、HC-CDR2和HC-CDR3；以及VL，其包含如氨基酸序列SEQ ID NO:72所示的VL包含的LC-CDR1、LC-CDR2和LC-CDR3。
在一些实施例中，所述抗LIGHT抗体包含VH，其包含如氨基酸序列SEQ ID NO:85所示的VH包含的HC-CDR1、HC-CDR2和HC-CDR3；以及VL，其包含如氨基酸序列SEQ ID NO:90所示的VL包含的LC-CDR1、LC-CDR2和LC-CDR3。
在一些实施例中，所述抗LIGHT抗体包含：VH，所述VH包含SEQ ID NOs:60，84-85中任一所示的氨基酸序列或其变体，所述变体与SEQ ID NOs:60，84-85中任一所示的氨基酸序列具有至少约80％(例如至少80％、85％、90％、95％、96％、97％、98％或99％)序列同一性；以及VL，所述VL包含SEQ ID NOs:72，86-91中任一所示的氨基酸序列或其变体，所述变体与SEQ ID NOs:72，86-91中任一所示的氨基酸序列具有至少约80％(例如至少80％、85％、90％、95％、96％、97％、98％或99％)序列同一性。在一些实施例中，所述抗LIGHT抗体包含VH，所述VH包含SEQ ID NOs:60，84-85中任一所示的氨基酸序列，以及VL，所述VL包含SEQ ID NOs:72，86-91中任一所示的氨基酸序列。
在一些实施例中，所述抗LIGHT抗体包含：VH，所述VH包含氨基酸序列SEQ ID NO:60或其变体，所述变体与氨基酸序列SEQ ID NO:60具有至少约80％(例如至少80％、85％、90％、95％、96％、97％、98％或99％)序列同一性；以及VL，所述VL包含氨基酸序列SEQ ID NO:72或其变体，所述变体与氨基酸序列SEQ ID NO:72具有至少约80％(例如至少80％、85％、90％、95％、96％、97％、98％或99％)序列同一性。在一些实施例中，所述抗LIGHT抗体包含VH，所述VH包含氨基酸序列SEQ ID NO:60，以及VL，所述VL包含氨基酸序列SEQ ID NO:72。
在一些实施例中，所述抗LIGHT抗体包含：VH，所述VH包含氨基酸序列SEQ ID NO:84或其变体，所述变体与氨基酸序列SEQ ID NO:84具有至少约80％(例如至少80％、85％、90％、95％、96％、97％、98％或99％)序列同一性；以及VL，所述VL包含氨基酸序列SEQ ID NO:86或其变体，所述变体与氨基酸序列SEQ ID NO:86具有至少约80％(例如至少80％、85％、90％、 95％、96％、97％、98％或99％)序列同一性。在一些实施例中，所述抗LIGHT抗体包含VH，所述VH包含氨基酸序列SEQ ID NO:84，以及VL，所述VL包含氨基酸序列SEQ ID NO:86。
在一些实施例中，所述抗LIGHT抗体包含：VH，所述VH包含氨基酸序列SEQ ID NO:85或其变体，所述变体与氨基酸序列SEQ ID NO:85具有至少约80％(例如至少80％、85％、90％、95％、96％、97％、98％或99％)序列同一性；以及VL，所述VL包含氨基酸序列SEQ ID NO:87或其变体，所述变体与氨基酸序列SEQ ID NO:87具有至少约80％(例如至少80％、85％、90％、95％、96％、97％、98％或99％)序列同一性。在一些实施例中，所述抗LIGHT抗体包含VH，所述VH包含氨基酸序列SEQ ID NO:85，以及VL，所述VL包含氨基酸序列SEQ ID NO:87。
在一些实施例中，所述抗LIGHT抗体包含：VH，所述VH包含氨基酸序列SEQ ID NO:84或其变体，所述变体与氨基酸序列SEQ ID NO:84具有至少约80％(例如至少80％、85％、90％、95％、96％、97％、98％或99％)序列同一性；以及VL，所述VL包含氨基酸序列SEQ ID NO:88或其变体，所述变体与氨基酸序列SEQ ID NO:88具有至少约80％(例如至少80％、85％、90％、95％、96％、97％、98％或99％)序列同一性。在一些实施例中，所述抗LIGHT抗体包含VH，所述VH包含氨基酸序列SEQ ID NO:84，以及VL，所述VL包含氨基酸序列SEQ ID NO:88。
在一些实施例中，所述抗LIGHT抗体包含：VH，所述VH包含氨基酸序列SEQ ID NO:84或其变体，所述变体与氨基酸序列SEQ ID NO:84具有至少约80％(例如至少80％、85％、90％、95％、96％、97％、98％或99％)序列同一性；以及VL，所述VL包含氨基酸序列SEQ ID NO:89或其变体，所述变体与氨基酸序列SEQ ID NO:89具有至少约80％(例如至少80％、85％、90％、95％、96％、97％、98％或99％)序列同一性。在一些实施例中，所述抗LIGHT抗体包含VH，所述VH包含氨基酸序列SEQ ID NO:84，以及VL，所述VL包含氨基酸序列SEQ ID NO:89。
在一些实施例中，所述抗LIGHT抗体包含：VH，所述VH包含氨基酸序列SEQ ID NO:85或其变体，所述变体与氨基酸序列SEQ ID NO:85具有至少约80％(例如至少80％、85％、90％、95％、96％、97％、98％或99％)序列同一性；以及VL，所述VL包含氨基酸序列SEQ ID NO:90或其变体，所述变体与氨基酸序列SEQ ID NO:90具有至少约80％(例如至少80％、85％、90％、95％、96％、97％、98％或99％)序列同一性。在一些实施例中，所述抗LIGHT抗体包含VH，所述VH包含氨基酸序列SEQ ID NO:85，以及VL，所述VL包含氨基酸序列SEQ ID NO:90。
在一些实施例中，所述抗LIGHT抗体包含：VH，所述VH包含氨基酸序列SEQ ID NO:84或其变体，所述变体与氨基酸序列SEQ ID NO:84具有至少约80％(例如至少80％、85％、90％、95％、96％、97％、98％或99％)序列同一性；以及VL，所述VL包含氨基酸序列SEQ ID NO:91或其变体，所述变体与氨基酸序列SEQ ID NO:91具有至少约80％(例如至少80％、85％、90％、95％、96％、97％、98％或99％)序列同一性。在一些实施例中，所述抗LIGHT抗体包含VH，所述VH包含氨基酸序列SEQ ID NO:84，以及VL，所述VL包含氨基酸序列SEQ ID NO:91。
在一些实施例中，所述抗LIGHT抗体，包含重链可变结构域(VH)，所述VH包含：重链互补决定区(HC-CDR)1，其包含SYNVH(SEQ ID NO:7)；HC-CDR2，其包含 AVYPGNGDTSYNQKFKG(SEQ ID NO:15)；和HC-CDR3，其包含GSYYYTSSYFDH(SEQ ID NO:22)；以及轻链可变结构域(VL)，所述VL包含：轻链互补决定区(LC-CDR)1，其包含KASQSVDFDGDSYMN(SEQ ID NO:29)；LC-CDR2，其包含TASNLES(SEQ ID NO:36)；和LC-CDR3，其包含QQSYEDPFT(SEQ ID NO:44)。
在一些实施例中，所述抗LIGHT抗体包含VH，所述VH包含：HC-CDR1，其包含SEQ ID NO:7所示的氨基酸序列或其变体，所述变体包含至多约3个(例如1、2或3个)氨基酸的取代；HC-CDR2，其包含SEQ ID NO:15所示的氨基酸序列或其变体，所述变体包含至多约3个(例如1、2或3个)氨基酸的取代；和HC-CDR3，其包含SEQ ID NO:22所示的氨基酸序列或其变体，所述变体包含至多约3个(例如1、2或3个)氨基酸的取代。
在一些实施例中，所述抗LIGHT抗体包含VH，所述VH包含：HC-CDR1，其包含SEQ ID NO:7所示的氨基酸序列，HC-CDR2，其包含SEQ ID NO:15所示的氨基酸序列，HC-CDR3，其包含SEQ ID NO:22所示的氨基酸序列。
在一些实施例中，所述抗LIGHT抗体包含VL，所述VL包含：LC-CDR1，其包含SEQ ID NO:29所示的氨基酸序列或其变体，所述变体包含至多约3个(例如1、2或3个)氨基酸的取代；LC-CDR2，其包含SEQ ID NO:36所示的氨基酸序列或其变体，所述变体包含至多约3个(例如1、2或3个)氨基酸的取代；和LC-CDR3，其包含SEQ ID NO:44所示的氨基酸序列或其变体，所述变体包含至多约3个(例如1、2或3个)氨基酸的取代。
在一些实施例中，所述抗LIGHT抗体包含VL，所述VL包含：LC-CDR1，其包含SEQ ID NO:29所示的氨基酸序列，LC-CDR2，其包含SEQ ID NO:36所示的氨基酸序列，LC-CDR3，其包含SEQ ID NO:44所示的氨基酸序列。
在一些实施例中，所述抗LIGHT抗体包含VH，所述VH包含：HC-CDR1，其包含SEQ ID NO:7所示的氨基酸序列或其变体，所述变体包含至多约3个(例如1、2或3个)氨基酸的取代；HC-CDR2，其包含SEQ ID NO:15所示的氨基酸序列或其变体，所述变体包含至多约3个(例如1、2或3个)氨基酸的取代；和HC-CDR3，其包含SEQ ID NO:22所示的氨基酸序列或其变体，所述变体包含至多约3个(例如1、2或3个)氨基酸的取代；以及VL，所述VL包含：LC-CDR1，其包含SEQ ID NO:29所示的氨基酸序列或其变体，所述变体包含至多约3个(例如1、2或3个)氨基酸的取代；LC-CDR2，其包含SEQ ID NO:36所示的氨基酸序列或其变体，所述变体包含至多约3个(例如1、2或3个)氨基酸的取代；和LC-CDR3，其包含SEQ ID NO:44所示的氨基酸序列或其变体，所述变体包含至多约3个(例如1、2或3个)氨基酸的取代。
在一些实施例中，所述抗LIGHT抗体包含VH，所述VH包含：HC-CDR1，其包含SEQ ID NO:7所示的氨基酸序列，HC-CDR2，其包含SEQ ID NO:15所示的氨基酸序列，和HC-CDR3，其包含SEQ ID NO:22所示的氨基酸序列；以及VL，所述VL包含：LC-CDR1，其包含SEQ ID NO:29所示的氨基酸序列，LC-CDR2，其包含SEQ ID NO:36所示的氨基酸序列，和LC-CDR3，其包含SEQ ID NO:44所示的氨基酸序列。
在一些实施例中，所述抗LIGHT抗体包含VH，所述VH包含：HC-CDR1，其包含氨基酸序列SEQ ID NO:7，HC-CDR2，其包含氨基酸序列SEQ ID NO:15，HC-CDR3，其包含氨基酸序列SEQ ID NO:22，或者所述VH的变体，其HC-CDRs中包含至多约5个氨基酸的取代；以及VL，所述VL包含：LC-CDR1，其包含氨基酸序列SEQ ID NO:29，LC-CDR2，其包含氨基酸序列SEQ ID NO:36，LC-CDR3，其包含氨基酸序列SEQ ID NO:44，或者所述VL的变体，其LC-CDRs中包含至多约5个氨基酸的取代。
在一些实施例中，所述抗LIGHT抗体包含VH，所述VH包含：HC-CDR1，其包含氨基酸序列SEQ ID NO:7，HC-CDR2，其包含氨基酸序列SEQ ID NO:15，和HC-CDR3，其包含氨基酸序列SEQ ID NO:22；以及VL，所述VL包含：LC-CDR1，其包含氨基酸序列SEQ ID NO:29，LC-CDR2，其包含氨基酸序列SEQ ID NO:36，和LC-CDR3，其包含氨基酸序列SEQ ID NO:44。
在一些实施例中，所述抗LIGHT抗体包含VH，所述VH包含如SEQ ID NOs:61，92-94中任一氨基酸序列所示的VH包含的HC-CDR1、HC-CDR2和HC-CDR3；以及VL，所述VL包含如SEQ ID NOs:73，95-99中任一氨基酸序列所示的VL包含的LC-CDR1、LC-CDR2和LC-CDR3。
在一些实施例中，所述抗LIGHT抗体包含VH，其包含如氨基酸序列SEQ ID NO:61所示的VH包含的HC-CDR1、HC-CDR2和HC-CDR3；以及VL，其包含如氨基酸序列SEQ ID NO:73所示的VL包含的LC-CDR1、LC-CDR2和LC-CDR3。
在一些实施例中，所述抗LIGHT抗体包含：VH，所述VH包含SEQ ID NOs:61，92-94中任一所示的氨基酸序列或其变体，所述变体与SEQ ID NOs:61，92-94中任一所示的氨基酸序列具有至少约80％(例如至少80％、85％、90％、95％、96％、97％、98％或99％)序列同一性；以及VL，所述VL包含SEQ ID NOs:73，95-99中任一所示的氨基酸序列或其变体，所述变体与SEQ ID NOs:73，95-99中任一所示的氨基酸序列具有至少约80％(例如至少80％、85％、90％、95％、96％、97％、98％或99％)序列同一性。在一些实施例中，所述抗LIGHT抗体包含VH，所述VH包含SEQ ID NOs:61，92-94中任一所示的氨基酸序列，以及VL，所述VL包含SEQ ID NOs:73，95-99中任一所示的氨基酸序列。
在一些实施例中，所述抗LIGHT抗体包含：VH，所述VH包含氨基酸序列SEQ ID NO:61或其变体，所述变体与氨基酸序列SEQ ID NO:61具有至少约80％(例如至少80％、85％、90％、95％、96％、97％、98％或99％)序列同一性；以及VL，所述VL包含氨基酸序列SEQ ID NO:73或其变体，所述变体与氨基酸序列SEQ ID NO:73具有至少约80％(例如至少80％、85％、90％、95％、96％、97％、98％或99％)序列同一性。在一些实施例中，所述抗LIGHT抗体包含VH，所述VH包含氨基酸序列SEQ ID NO:61，以及VL，所述VL包含氨基酸序列SEQ ID NO:73。
在一些实施例中，所述抗LIGHT抗体包含：VH，所述VH包含氨基酸序列SEQ ID NO:92或其变体，所述变体与氨基酸序列SEQ ID NO:92具有至少约80％(例如至少80％、85％、90％、95％、96％、97％、98％或99％)序列同一性；以及VL，所述VL包含氨基酸序列SEQ ID NO:95或其变体，所述变体与氨基酸序列SEQ ID NO:95具有至少约80％(例如至少80％、85％、90％、 95％、96％、97％、98％或99％)序列同一性。在一些实施例中，所述抗LIGHT抗体包含VH，所述VH包含氨基酸序列SEQ ID NO:92，以及VL，所述VL包含氨基酸序列SEQ ID NO:95。
在一些实施例中，所述抗LIGHT抗体包含：VH，所述VH包含氨基酸序列SEQ ID NO:93或其变体，所述变体与氨基酸序列SEQ ID NO:93具有至少约80％(例如至少80％、85％、90％、95％、96％、97％、98％或99％)序列同一性；以及VL，所述VL包含氨基酸序列SEQ ID NO:96或其变体，所述变体与氨基酸序列SEQ ID NO:96具有至少约80％(例如至少80％、85％、90％、95％、96％、97％、98％或99％)序列同一性。在一些实施例中，所述抗LIGHT抗体包含VH，所述VH包含氨基酸序列SEQ ID NO:93，以及VL，所述VL包含氨基酸序列SEQ ID NO:96。
在一些实施例中，所述抗LIGHT抗体包含：VH，所述VH包含氨基酸序列SEQ ID NO:92或其变体，所述变体与氨基酸序列SEQ ID NO:92具有至少约80％(例如至少80％、85％、90％、95％、96％、97％、98％或99％)序列同一性；以及VL，所述VL包含氨基酸序列SEQ ID NO:96或其变体，所述变体与氨基酸序列SEQ ID NO:96具有至少约80％(例如至少80％、85％、90％、95％、96％、97％、98％或99％)序列同一性。在一些实施例中，所述抗LIGHT抗体包含VH，所述VH包含氨基酸序列SEQ ID NO:92，以及VL，所述VL包含氨基酸序列SEQ ID NO:96。
在一些实施例中，所述抗LIGHT抗体包含：VH，所述VH包含氨基酸序列SEQ ID NO:94或其变体，所述变体与氨基酸序列SEQ ID NO:94具有至少约80％(例如至少80％、85％、90％、95％、96％、97％、98％或99％)序列同一性；以及VL，所述VL包含氨基酸序列SEQ ID NO:97或其变体，所述变体与氨基酸序列SEQ ID NO:97具有至少约80％(例如至少80％、85％、90％、95％、96％、97％、98％或99％)序列同一性。在一些实施例中，所述抗LIGHT抗体包含VH，所述VH包含氨基酸序列SEQ ID NO:94，以及VL，所述VL包含氨基酸序列SEQ ID NO:97。
在一些实施例中，所述抗LIGHT抗体包含：VH，所述VH包含氨基酸序列SEQ ID NO:94或其变体，所述变体与氨基酸序列SEQ ID NO:94具有至少约80％(例如至少80％、85％、90％、95％、96％、97％、98％或99％)序列同一性；以及VL，所述VL包含氨基酸序列SEQ ID NO:98或其变体，所述变体与氨基酸序列SEQ ID NO:98具有至少约80％(例如至少80％、85％、90％、95％、96％、97％、98％或99％)序列同一性。在一些实施例中，所述抗LIGHT抗体包含VH，所述VH包含氨基酸序列SEQ ID NO:94，以及VL，所述VL包含氨基酸序列SEQ ID NO:98。
在一些实施例中，所述抗LIGHT抗体包含：VH，所述VH包含氨基酸序列SEQ ID NO:93或其变体，所述变体与氨基酸序列SEQ ID NO:93具有至少约80％(例如至少80％、85％、90％、95％、96％、97％、98％或99％)序列同一性；以及VL，所述VL包含氨基酸序列SEQ ID NO:98或其变体，所述变体与氨基酸序列SEQ ID NO:98具有至少约80％(例如至少80％、85％、90％、95％、96％、97％、98％或99％)序列同一性。在一些实施例中，所述抗LIGHT抗体包含VH，所述VH包含氨基酸序列SEQ ID NO:93，以及VL，所述VL包含氨基酸序列SEQ ID NO:98。
在一些实施例中，所述抗LIGHT抗体包含：VH，所述VH包含氨基酸序列SEQ ID NO:92或其变体，所述变体与氨基酸序列SEQ ID NO:92具有至少约80％(例如至少80％、85％、90％、 95％、96％、97％、98％或99％)序列同一性；以及VL，所述VL包含氨基酸序列SEQ ID NO:98或其变体，所述变体与氨基酸序列SEQ ID NO:98具有至少约80％(例如至少80％、85％、90％、95％、96％、97％、98％或99％)序列同一性。在一些实施例中，所述抗LIGHT抗体包含VH，所述VH包含氨基酸序列SEQ ID NO:92，以及VL，所述VL包含氨基酸序列SEQ ID NO:98。
在一些实施例中，所述抗LIGHT抗体包含：VH，所述VH包含氨基酸序列SEQ ID NO:94或其变体，所述变体与氨基酸序列SEQ ID NO:94具有至少约80％(例如至少80％、85％、90％、95％、96％、97％、98％或99％)序列同一性；以及VL，所述VL包含氨基酸序列SEQ ID NO:99或其变体，所述变体与氨基酸序列SEQ ID NO:99具有至少约80％(例如至少80％、85％、90％、95％、96％、97％、98％或99％)序列同一性。在一些实施例中，所述抗LIGHT抗体包含VH，所述VH包含氨基酸序列SEQ ID NO:94，以及VL，所述VL包含氨基酸序列SEQ ID NO:99。
在一些实施例中，所述抗LIGHT抗体包含：VH，所述VH包含氨基酸序列SEQ ID NO:92或其变体，所述变体与氨基酸序列SEQ ID NO:92具有至少约80％(例如至少80％、85％、90％、95％、96％、97％、98％或99％)序列同一性；以及VL，所述VL包含氨基酸序列SEQ ID NO:99或其变体，所述变体与氨基酸序列SEQ ID NO:99具有至少约80％(例如至少80％、85％、90％、95％、96％、97％、98％或99％)序列同一性。在一些实施例中，所述抗LIGHT抗体包含VH，所述VH包含氨基酸序列SEQ ID NO:92，以及VL，所述VL包含氨基酸序列SEQ ID NO:99。
在一些实施例中，上述氨基酸取代限于本文表4中所示的“示例性取代”。在一些实施例中，氨基酸取代限于本文表4中所示的“优选取代”。
在一些实施例中，功能性表位可通过组合丙氨酸扫描法来解析。在此过程中，组合丙氨酸扫描技术可用于鉴定LIGHT蛋白中与抗LIGHT抗体相互作用所必需的氨基酸。在一些实施例中，该表位是构象的，同时可以采用与LIGHT蛋白结合的抗LIGHT抗体的晶体结构来鉴定表位。
在一些实施例中，本申请提供与本文所述的任一种抗LIGHT抗体竞争性结合LIGHT的抗体。在一些实施例中，提供能够与本文所述的任一种抗LIGHT抗体竞争性地结合LIGHT上的表位的抗体。在一些实施例中，提供抗LIGHT抗体，其与包含VH和VL的抗LIGHT抗体分子结合相同的表位，其中所述VH包含SEQ ID NOs:46-61，92-94中任一所示的氨基酸序列，以及所述VL包含SEQ ID NOs:62-73，95-99中任一所示的氨基酸序列。在一些实施例中，提供抗LIGHT抗体，其与包含VH和VL的抗LIGHT抗体竞争性地结合LIGHT，其中所述VH包含SEQ ID NOs:46-61，92-94中任一所示的氨基酸序列，以及所述VL包含SEQ ID NOs:62-73，95-99中任一所示的氨基酸序列。
在一些实施例中，可以利用竞争实验来鉴定与本文所述的抗LIGHT抗体竞争性结合LIGHT的单克隆抗体。竞争实验可以通过识别相同的或空间上重叠的表位或者通过一个抗体竞争性抑制另一抗体与抗原结合来确定两个抗体是否结合相同的表位。在某些实施例中，这种竞争性抗体与本文所述的抗体结合相同的表位。一些示例性的竞争实验包括，但不限于如Harlow and Lane(1988)Antibodies:A Laboratory Manual ch.14(Cold Spring Harbor Laboratory，Cold Spring Harbor, N.Y.)中所提到的常规实验。用于解析抗体结合的表位的详细示例性方法如Morris(1996)"Epitope Mapping Protocols,"in Methods in Molecular Biology vol.66(Humana Press,Totowa,N.J.)中所述。在一些实施例中，如果每种抗体阻断另一种抗体结合的50％或更多，则称其结合相同的表位。在一些实施例中，与本文所述的抗LIGHT抗体竞争的抗体是嵌合抗体、人源化抗体或全人抗体。
示例性抗LIGHT抗体序列如表2、表3所示，其中根据Kabat定义方式进行CDR编号。本领域技术人员将认识到有多种已知算法来预测CDR的位置以及界定抗体轻、重链可变区。包含如本文所述抗体的CDRs、VH和/或VL序列，但基于预测算法而非下表中所示例的抗体也在本申请的范围内。
表2示例性抗LIGHT抗体CDR序列


表2A示例性抗LIGHT抗体CDR序列
表2B示例性抗LIGHT抗体CDR序列

表3示例性序列



表3A示例性序列
表3B示例性序列
LIGHT
LIGHT(T淋巴细胞上可诱导表达的淋巴毒素样的与单疱疹病毒糖蛋白D竞争结合HVEM的受体)，作为肿瘤坏死因子超家族(TNFSF)的成员之一，是一个包含240个氨基酸的II型跨膜蛋白，形成一个细胞表面的同源三聚体。LIGHT也被称为肿瘤坏死因子超家族成员14(TNFSF14)、TL5、LTg、HVEML或CD258。LIGHT是T细胞协同刺激分子，能够诱导T细胞增殖和细胞因子的产生(Tamada等人，2000,Nat Med)。LIGHT也能诱导单核细胞和内皮细胞中的炎症反应(Otterda等人，2006，Blood；Chang等人，2005，J Biomed Sci)。LIGHT结合于在不同细胞类型上表达的3个不同的受体：在T细胞和B细胞上表达的疱疹病毒进入调节子HVEM，在基质细胞和非造血细胞上表达的淋巴毒素β受体LTβR和诱骗受体3。树突细胞和T细胞上的LIGHT增强了T细胞增殖和细胞因子的产生。LIGHT可直接协同刺激T细胞反应。LIGHT在各种炎症疾病和病症中的作用已通过使用LIGHT缺陷型模型和LIGHT过表达转基因动物的各种模型所 证明。LIGHT在小鼠中的过表达导致活化的外周T细胞群过度过度产生和严重的自身免疫性疾病的自发产生(Wang等人，2001，J Clin Invest.)。
LIGHT受体
LIGHT通过结合淋巴毒素β受体(LTβR)(Crowe等人，1994，Science 264707-10，Browning等人，1997，J Immunol 159 3288-98)、单纯疱疹病毒进入介导子(HVEM)(Montgomery等人，1996，Cell 87(3)427-36)以及诱骗受体3(DcR3)(Yu等人，1999，J Biol Chem 274 13733-6)在内的三个TNF超家族受体介导其生物学作用。
淋巴毒素β受体(LTβR)信号协调淋巴细胞新生和随后的三级淋巴结构(TLS)，与多个器官系统的严重慢性炎症性疾病有关。Conlon TM等人的研究证明了抑制LTβR信号通路能够激活Wnt诱导的肺再生(Conlon TM等人，2020，Nature 588(7836):151-156)。该研究证明了吸烟相关的慢性阻塞性肺疾病(COPD)患者和暴露于慢性香烟烟雾的小鼠的肺上皮细胞中，LTβR的配体包括LTα，LTβ和LIGHT在适应性和固有免疫细胞上的表达增加，非典型NF-κB信号通路增强，并富集了LTβR靶基因的表达。在年轻和年老小鼠中通过LTβR-Ig多肽治疗性抑制LTβR信号通路能够破坏吸烟相关的诱导性支气管相关淋巴组织(iBALT)，诱导肺组织再生，并恢复气道纤维化和系统性肌肉萎缩。从机制上讲，LTβR信号阻断抑制了上皮非典型NF-κB的活化，降低了气道中TGFβ信号转导，通过防止上皮细胞死亡和激活肺泡上皮前体细胞中的Wnt/β-catenin信号转导来诱导再生。
活化T细胞上的LIGHT能够直接向表达HVEM的其他T细胞传递信号，也可以通过未成熟的DC细胞或SC细胞上表达的HVEM和/或LTβR间接发挥作用，刺激这些辅助细胞分泌促炎因子。越来越多的实验证据表明表达于DC或T细胞上的LIGHT可以共刺激以及增强T细胞增殖和细胞因子的分泌(Tamada.K等人，2000，J.Immunol.164,4105-4110.)。与这些报道一致的是，向T细胞中加入LIGHT-Ig重组融合蛋白能够激活NF-κB和AP-1，共刺激T细胞增殖以及IFN-γ的分泌(Granger等人，2003，Cytokine Growth Factor Rev.14,289-296)。这种增强的T细胞激活是HVEM信号介导的，因为LTβR在成熟的T细胞上不表达。LIGHT与其他细胞类型表达的HVEM的相互作用也会引发各种功能活性。例如，表达于活化T细胞上的可溶性或膜结合LIGHT，与表达在未成熟的DC细胞上的HVEM相接触，当加入CD40L-Ig时，可以诱导DC细胞成熟并增强同种异体的刺激活性(Morel等人，2001，J.Immunol.167,2479-2486)。
有研究已经表明，组成型表达LIGHT的转基因小鼠被检测到超活化的T细胞群，使得小鼠发生自身免疫的风险增加，其特征表现为小鼠外周组织内的效应细胞严重浸润(Wang等人，2005，J Immunol 174 8173-82；Shaikh等人，2001，J Immunol 167 6330-7；Wang等人，2001，J Immunol 1675099-105；Wang等人，2004，J Clin Invest 113 826-35)。HVEM-LIGHT的相互作用能够促进移植物抗宿主病GVHD的发病机制。将hvem-/-或light-/-小鼠的同种异体T细胞移植到受体小鼠体内，会诱发减弱的抗宿主CTL反应，从而延长受体小鼠的生存期。hvem-/-和light-/-供体T细胞转移到受体小鼠体内后会发生凋亡。因此，施用抗HVEM的mAb，可以抑制HVEM-LIGHT的相互作 用，改善GVHD反应并延长受体小鼠的生存期(Xu等人，2007，Blood 109:4097–4104)。当来自LIGHT转基因动物的肠系膜淋巴结细胞被转移至RAG-/-时，表达LIGHT的淋巴细胞可诱导IBD样症状，例如人Crohn疾病、裂开性溃疡、回肠炎的细胞因子特征，以及结肠IFN-γ和TNF的增加(Wang等人，2005，J Immunol 174 8173-82)。在T细胞依赖的过敏性肺炎模型中，HVEM-LIGHT的相互作用在致病性记忆Th2细胞的生存中起主导作用。中断HVEM-LIGHT的相互作用抑制炎症记忆Th2细胞在肺部的积累。虽然light-/-供体CD4+T细胞在体内接触抗原后不能维持，但野生型和light-/-供体T细胞的共转移能挽救light-/-供体T细胞的生存缺陷，这表明HVEM通过与邻近抗原特异性T细胞上表达的LIGHT相互作用诱导细胞生存信号进入T细胞。这一研究表明由CD4+T细胞表达的HVEM能诱导细胞生存信号并控制T细胞驱动的过敏性肺炎(Soroosh等人，2011，J Exp Med 208:797–809)。
DcR3也被称为肿瘤坏死因子受体超家族成员6B(TNFRSF6B)，是LIGHT信号的功能衰减器，在人类基因组中发现，但在小鼠和大鼠中不存在。它是一个缺乏膜锚定的分子，通过结合LIGHT、Fas配体和TL1A作为一个可溶性抑制因子发挥作用。在人类中，DcR3结合LIGHT，并抑制HVEM和LIGHT的相互作用(Jiang M.2016，Med SciMonit.22:1850–7)。
全长抗LIGHT抗体
在一些实施例中，所述抗LIGHT抗体是全长抗LIGHT抗体。在一些实施例中，所述全长抗LIGHT抗体是IgA、IgD、IgE、IgG或IgM。在一些实施例中，所述全长抗LIGHT抗体包含IgG恒定区域，例如IgG1、IgG2、IgG3、IgG4或其变体的恒定区域。在一些实施例中，所述全长抗LIGHT抗体包含λ轻链恒定区。在一些实施例中，所述全长抗LIGHT抗体包含κ轻链恒定区。在一些实施例中，所述全长抗LIGHT抗体是全长的人抗LIGHT抗体。在一些实施例中，所述全长抗LIGHT抗体包含小鼠免疫球蛋白Fc序列。在一些实施例中，所述全长抗LIGHT抗体包含已经改变的或以其他方式改变的Fc序列，使得其具有增强的抗体依赖的细胞介导的细胞毒作用(ADCC)和补体依赖的细胞毒作用(CDC)的效应功能。
因此，例如，在一些实施例中，提供一种包含IgG1恒定区的全长抗LIGHT抗体，所述抗LIGHT抗体与LIGHT特异性结合。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG2恒定区的全长抗LIGHT抗体，所述抗LIGHT抗体与LIGHT特异性结合。在一些实施例中，所述IgG2是人IgG2。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG3恒定区的全长抗LIGHT抗体，所述抗LIGHT抗体与LIGHT特异性结合。在一些实施例中，所述IgG3是人IgG3。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG4恒定区的全长抗LIGHT抗体，所述抗LIGHT抗体与LIGHT特异性结合。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG1恒定区的全长抗LIGHT抗体，其中所述抗LIGHT抗体包含：a)重链可变结构域，所述重链可变结构域包含：HC-CDR1，其包含SEQ ID NOs:1-7中任一所示的氨基酸序列或其变体，所述变体包含至多约3个(例如1、2或3个)氨基酸的取代；HC-CDR2，其包含SEQ ID NOs:8-15中任一所示的氨基酸序列或其变体，所述变体包含至多约3个(例如1、2或3个)氨基酸的取代；和HC-CDR3，其包含SEQ ID NOs:16-22中任一所示的氨基酸序列或其变体，所述变体包含至多约3个(例如1、2或3个)氨基酸的取代；以及b)轻链可变结构域，所述轻链可变结构域包含：LC-CDR1，其包含SEQ ID NOs:23-29，83中任一所示的氨基酸序列或其变体，所述变体包含至多约3个(例如1、2或3个)氨基酸的取代，LC-CDR2，其包含SEQ ID NOs:30-36中任一所示的氨基酸序列或其变体，所述变体包含至多约3个(例如1、2或3个)氨基酸的取代；和LC-CDR3，其包含SEQ ID NOs:37-44中任一所示的氨基酸序列或其变体，所述变体包含至多约3个(例如1、2或3个)氨基酸的取代。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG2恒定区的全长抗LIGHT抗体，其中所述抗LIGHT抗体包含：a)重链可变结构域，所述重链可变结构域包含：HC-CDR1，其包含SEQ ID NOs:1-7中任一所示的氨基酸序列或其变体，所述变体包含至多约3个(例如1、2或3个)氨基酸的取代；HC-CDR2，其包含SEQ ID NOs:8-15中任一所示的氨基酸序列或其变体，所述变体包含至多约3个(例如1、2或3个)氨基酸的取代；和HC-CDR3，其包含SEQ ID NOs:16-22中任一所示的氨基酸序列或其变体，所述变体包含至多约3个(例如1、2或3个)氨基酸的取代；以及b)轻链可变 结构域，所述轻链可变结构域包含：LC-CDR1，其包含SEQ ID NOs:23-29，83中任一所示的氨基酸序列或其变体，所述变体包含至多约3个(例如1、2或3个)氨基酸的取代；LC-CDR2，其包含SEQ ID NOs:30-36中任一所示的氨基酸序列或其变体，所述变体包含至多约3个(例如1、2或3个)氨基酸的取代；和LC-CDR3，其包含SEQ ID NOs:37-44中任一所示的氨基酸序列或其变体，所述变体包含至多约3个(例如1、2或3个)氨基酸的取代。在一些实施例中，所述IgG2是人IgG2。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG3恒定区的全长抗LIGHT抗体，其中所述抗LIGHT抗体包含：a)重链可变结构域，所述重链可变结构域包含：HC-CDR1，其包含SEQ ID NOs:1-7中任一所示的氨基酸序列或其变体，所述变体包含至多约3个(例如1、2或3个)氨基酸的取代，HC-CDR2，其包含SEQ ID NOs:8-15中任一所示的氨基酸序列或其变体，所述变体包含至多约3个(例如1、2或3个)氨基酸的取代；和HC-CDR3，其包含SEQ ID NOs:16-22中任一所示的氨基酸序列或其变体，所述变体包含至多约3个(例如1、2或3个)氨基酸的取代；以及b)轻链可变结构域，所述轻链可变结构域包含：LC-CDR1，其包含SEQ ID NOs:23-29，83中任一所示的氨基酸序列或其变体，所述变体包含至多约3个(例如1、2或3个)氨基酸的取代；LC-CDR2，其包含SEQ ID NOs:30-36中任一所示的氨基酸序列或其变体，所述变体包含至多约3个(例如1、2或3个)氨基酸的取代；和LC-CDR3，其包含SEQ ID NOs:37-44中任一所示的氨基酸序列或其变体，所述变体包含至多约3个(例如1、2或3个)氨基酸的取代。在一些实施例中，所述IgG3是人IgG3。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG4恒定区的全长抗LIGHT抗体，其中所述抗LIGHT抗体包含：a)重链可变结构域，所述重链可变结构域包含：HC-CDR1，其包含SEQ ID NOs:1-7中任一所示的氨基酸序列或其变体，所述变体包含至多约3个(例如1、2或3个)氨基酸的取代；HC-CDR2，其包含SEQ ID NOs:8-15中任一所示的氨基酸序列或其变体，所述变体包含至多约3个(例如1、2或3个)氨基酸的取代；和HC-CDR3，其包含SEQ ID NOs:16-22中任一所示的氨基酸序列或其变体，所述变体包含至多约3个(例如1、2或3个)氨基酸的取代；以及b)轻链可变结构域，所述轻链可变结构域包含：LC-CDR1，其包含SEQ ID NOs:23-29，83中任一所示的氨基酸序列或其变体，所述变体包含至多约3个(例如1、2或3个)氨基酸的取代，LC-CDR2，其包含SEQ ID NOs:30-36中任一所示的氨基酸序列或其变体，所述变体包含至多约3个(例如1、2或3个)氨基酸的取代，和LC-CDR3，其包含SEQ ID NOs:37-44中任一所示的氨基酸序列或其变体，所述变体包含至多约3个(例如1、2或3个)氨基酸的取代。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO: 75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG1恒定区的全长抗LIGHT抗体，其中所述抗LIGHT抗体包含：a)重链可变结构域，所述重链可变结构域包含：HC-CDR1，其包含SEQ ID NOs:1-7中任一所示的氨基酸序列，HC-CDR2，其包含SEQ ID NOs:8-15中任一所示的氨基酸序列，和HC-CDR3，其包含SEQ ID NOs:16-22中任一所示的氨基酸序列，或者所述重链可变结构域的变体，其HC-CDR序列中包含至多约5个(例如1、2、3、4或5个)氨基酸的取代；以及b)轻链可变结构域，所述轻链可变结构域包含：LC-CDR1，其包含SEQ ID NOs:23-29，83中任一所示的氨基酸序列，LC-CDR2，其包含SEQ ID NOs:30-36中任一所示的氨基酸序列，和LC-CDR3，其包含SEQ ID NOs:37-44中任一所示的氨基酸序列，或者所述轻链可变结构域的变体，其LC-CDR序列中包含至多约5个(例如1、2、3、4或5个)氨基酸的取代。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG4恒定区的全长抗LIGHT抗体，其中所述抗LIGHT抗体包含a)重链可变结构域，所述重链可变结构域包含：HC-CDR1，其包含SEQ ID NOs:1-7中任一所示的氨基酸序列，HC-CDR2，其包含SEQ ID NOs:8-15中任一所示的氨基酸序列，和HC-CDR3，其包含SEQ ID NOs:16-22中任一所示的氨基酸序列，或者所述重链可变结构域的变体，其HC-CDR序列中包含至多约5个(例如1、2、3、4或5个)氨基酸的取代；以及b)轻链可变结构域，所述轻链可变结构域包含：LC-CDR1，其包含SEQ ID NOs:23-29，83中任一所示的氨基酸序列，LC-CDR2，包含SEQ ID NOs:30-36中任一所示的氨基酸序列，和LC-CDR3，其包含SEQ ID NOs:37-44中任一所示的氨基酸序列，或者所述轻链可变结构域的变体，其LC-CDR序列中包含至多约5个(例如1、2、3、4或5个)氨基酸的取代。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG1恒定区的全长抗LIGHT抗体，其中所述抗LIGHT抗体包含：a)重链可变结构域，所述重链可变结构域包含：HC-CDR1，其包含SEQ ID NOs:1-7中任一所示的氨基酸序列，HC-CDR2，其包含SEQ ID NOs:8-15中任一所示的氨基酸序列，和HC- CDR3，其包含SEQ ID NOs:16-22中任一所示的氨基酸序列；以及b)轻链可变结构域，所述轻链可变结构域包含：LC-CDR1，其包含SEQ ID NOs:23-29，83中任一所示的氨基酸序列，LC-CDR2，其包含SEQ ID NOs:30-36中任一所示的氨基酸序列，和LC-CDR3，其包含SEQ ID NOs:37-44中任一所示的氨基酸序列。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG4恒定区的全长抗LIGHT抗体，其中所述抗LIGHT抗体包含：a)重链可变结构域，所述重链可变结构域包含：HC-CDR1，其包含SEQ ID NOs:1-7中任一所示的氨基酸序列，HC-CDR2，其包含SEQ ID NOs:8-15中任一所示的氨基酸序列，和HC-CDR3，其包含SEQ ID NOs:16-22中任一所示的氨基酸序列；以及b)轻链可变结构域，所述轻链可变结构域包含：LC-CDR1，其包含SEQ ID NOs:23-29，83中任一所示的氨基酸序列，LC-CDR2，其包含SEQ ID NOs:30-36中任一所示的氨基酸序列，和LC-CDR3，其包含SEQ ID NOs:37-44中任一所示的氨基酸序列。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG1恒定区的全长抗LIGHT抗体，其中所述抗LIGHT抗体包含：a)重链可变结构域，所述重链可变结构域包含：HC-CDR1，其包含氨基酸序列SEQ ID NO:1，HC-CDR2，其包含氨基酸序列SEQ ID NO:8，和HC-CDR3，其包含氨基酸序列SEQ ID NO:16；以及b)轻链可变结构域，所述轻链可变结构域包含：LC-CDR1，其包含氨基酸序列SEQ ID NO:23，LC-CDR2，其包含氨基酸序列SEQ ID NO:30，和LC-CDR3，其包含氨基酸序列SEQ ID NO:37。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG1恒定区的全长抗LIGHT抗体，其中所述抗LIGHT抗体包含：a)重链可变结构域，所述重链可变结构域包含：HC-CDR1，其包含氨基酸序列SEQ ID NO: 1，HC-CDR2，其包含氨基酸序列SEQ ID NO:9，和HC-CDR3，其包含氨基酸序列SEQ ID NO:16；以及b)轻链可变结构域，所述轻链可变结构域包含：LC-CDR1，其包含氨基酸序列SEQ ID NO:23，LC-CDR2，其包含氨基酸序列SEQ ID NO:30，和LC-CDR3，其包含氨基酸序列SEQ ID NO:37。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG1恒定区的全长抗LIGHT抗体，其中所述抗LIGHT抗体包含：a)重链可变结构域，所述重链可变结构域包含：HC-CDR1，其包含氨基酸序列SEQ ID NO:2，HC-CDR2，其包含氨基酸序列SEQ ID NO:10，和HC-CDR3，其包含氨基酸序列SEQ ID NO:17；以及b)轻链可变结构域，所述轻链可变结构域包含：LC-CDR1，其包含氨基酸序列SEQ ID NO:24，LC-CDR2，其包含氨基酸序列SEQ ID NO:31，和LC-CDR3，其包含氨基酸序列SEQ ID NO:38。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG1恒定区的全长抗LIGHT抗体，其中所述抗LIGHT抗体包含：a)重链可变结构域，所述重链可变结构域包含：HC-CDR1，其包含氨基酸序列SEQ ID NO:2，HC-CDR2，其包含氨基酸序列SEQ ID NO:10，和HC-CDR3，其包含氨基酸序列SEQ ID NO:17；以及b)轻链可变结构域，所述轻链可变结构域包含：LC-CDR1，其包含氨基酸序列SEQ ID NO:25，LC-CDR2，其包含氨基酸序列SEQ ID NO:31，和LC-CDR3，其包含氨基酸序列SEQ ID NO:39。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG1恒定区的全长抗LIGHT抗体，其中所述抗LIGHT抗体包含：a)重链可变结构域，所述重链可变结构域包含：HC-CDR1，其包含氨基酸序列SEQ ID NO:3，HC-CDR2，其包含氨基酸序列SEQ ID NO:11，和HC-CDR3，其包含氨基酸序列SEQ ID NO: 18；以及b)轻链可变结构域，所述轻链可变结构域包含：LC-CDR1，其包含氨基酸序列SEQ ID NO:26，LC-CDR2，其包含氨基酸序列SEQ ID NO:32，和LC-CDR3，其包含氨基酸序列SEQ ID NO:40。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG1恒定区的全长抗LIGHT抗体，其中所述抗LIGHT抗体包含：a)重链可变结构域，所述重链可变结构域包含：HC-CDR1，其包含氨基酸序列SEQ ID NO:3，HC-CDR2，其包含氨基酸序列SEQ ID NO:11，和HC-CDR3，其包含氨基酸序列SEQ ID NO:18；以及b)轻链可变结构域，所述轻链可变结构域包含：LC-CDR1，其包含氨基酸序列SEQ ID NO:26，LC-CDR2，其包含氨基酸序列SEQ ID NO:32，和LC-CDR3，其包含氨基酸序列SEQ ID NO:41。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG1恒定区的全长抗LIGHT抗体，其中所述抗LIGHT抗体包含：a)重链可变结构域，所述重链可变结构域包含：HC-CDR1，其包含氨基酸序列SEQ ID NO:4，HC-CDR2，其包含氨基酸序列SEQ ID NO:12，和HC-CDR3，其包含氨基酸序列SEQ ID NO:19；以及b)轻链可变结构域，所述轻链可变结构域包含：LC-CDR1，其包含氨基酸序列SEQ ID NO:27，LC-CDR2，其包含氨基酸序列SEQ ID NO:33，和LC-CDR3，其包含氨基酸序列SEQ ID NO:42。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG1恒定区的全长抗LIGHT抗体，其中所述抗LIGHT抗体包含：a)重链可变结构域，所述重链可变结构域包含：HC-CDR1，其包含氨基酸序列SEQ ID NO:5，HC-CDR2，其包含氨基酸序列SEQ ID NO:13，和HC-CDR3，其包含氨基酸序列SEQ ID NO:20；以及b)轻链可变结构域，所述轻链可变结构域包含：LC-CDR1，其包含氨基酸序列SEQ ID  NO:28，LC-CDR2，其包含氨基酸序列SEQ ID NO:34，和LC-CDR3，其包含氨基酸序列SEQ ID NO:43。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG1恒定区的全长抗LIGHT抗体，其中所述抗LIGHT抗体包含：a)重链可变结构域，所述重链可变结构域包含：HC-CDR1，其包含氨基酸序列SEQ ID NO:6，HC-CDR2，其包含氨基酸序列SEQ ID NO:14，和HC-CDR3，其包含氨基酸序列SEQ ID NO:21；以及b)轻链可变结构域，所述轻链可变结构域包含：LC-CDR1，其包含氨基酸序列SEQ ID NO:29，LC-CDR2，其包含氨基酸序列SEQ ID NO:35，和LC-CDR3，其包含氨基酸序列SEQ ID NO:43。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG1恒定区的全长抗LIGHT抗体，其中所述抗LIGHT抗体包含：a)重链可变结构域，所述重链可变结构域包含：HC-CDR1，其包含氨基酸序列SEQ ID NO:6，HC-CDR2，其包含氨基酸序列SEQ ID NO:14，和HC-CDR3，其包含氨基酸序列SEQ ID NO:21；以及b)轻链可变结构域，所述轻链可变结构域包含：LC-CDR1，其包含氨基酸序列SEQ ID NO:83，LC-CDR2，其包含氨基酸序列SEQ ID NO:35，和LC-CDR3，其包含氨基酸序列SEQ ID NO:43。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG1恒定区的全长抗LIGHT抗体，其中所述抗LIGHT抗体包含：a)重链可变结构域，所述重链可变结构域包含：HC-CDR1，其包含氨基酸序列SEQ ID NO:7，HC-CDR2，其包含氨基酸序列SEQ ID NO:15，和HC-CDR3，其包含氨基酸序列SEQ ID NO:22；以及b)轻链可变结构域，所述轻链可变结构域包含：LC-CDR1，其包含氨基酸序列SEQ ID NO:29，LC-CDR2，其包含氨基酸序列SEQ ID NO:36，和LC-CDR3，其包含氨基酸序列SEQ ID  NO:44。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG4恒定区的全长抗LIGHT抗体，其中所述抗LIGHT抗体包含：a)重链可变结构域，所述重链可变结构域包含：HC-CDR1，其包含氨基酸序列SEQ ID NO:1，HC-CDR2，其包含氨基酸序列SEQ ID NO:8，和HC-CDR3，其包含氨基酸序列SEQ ID NO:16；以及b)轻链可变结构域，所述轻链可变结构域包含：LC-CDR1，其包含氨基酸序列SEQ ID NO:23，LC-CDR2，其包含氨基酸序列SEQ ID NO:30，和LC-CDR3，其包含氨基酸序列SEQ ID NO:37。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG4恒定区的全长抗LIGHT抗体，其中所述抗LIGHT抗体包含：a)重链可变结构域，所述重链可变结构域包含：HC-CDR1，其包含氨基酸序列SEQ ID NO:1，HC-CDR2，其包含氨基酸序列SEQ ID NO:9，和HC-CDR3，其包含氨基酸序列SEQ ID NO:16；以及b)轻链可变结构域，所述轻链可变结构域包含：LC-CDR1，其包含氨基酸序列SEQ ID NO:23，LC-CDR2，其包含氨基酸序列SEQ ID NO:30，和LC-CDR3，其包含氨基酸序列SEQ ID NO:37。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG4恒定区的全长抗LIGHT抗体，其中所述抗LIGHT抗体包含：a)重链可变结构域，所述重链可变结构域包含：HC-CDR1，其包含氨基酸序列SEQ ID NO:2，HC-CDR2，其包含氨基酸序列SEQ ID NO:10，和HC-CDR3，其包含氨基酸序列SEQ ID NO:17；以及b)轻链可变结构域，所述轻链可变结构域包含：LC-CDR1，其包含氨基酸序列SEQ ID NO:24，LC-CDR2，其包含氨基酸序列SEQ ID NO:31，和LC-CDR3，其包含氨基酸序列SEQ ID NO:38。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序 列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG4恒定区的全长抗LIGHT抗体，其中所述抗LIGHT抗体包含：a)重链可变结构域，所述重链可变结构域包含：HC-CDR1，其包含氨基酸序列SEQ ID NO:2，HC-CDR2，其包含氨基酸序列SEQ ID NO:10，和HC-CDR3，其包含氨基酸序列SEQ ID NO:17；以及b)轻链可变结构域，所述轻链可变结构域包含：LC-CDR1，其包含氨基酸序列SEQ ID NO:25，LC-CDR2，其包含氨基酸序列SEQ ID NO:31，和LC-CDR3，其包含氨基酸序列SEQ ID NO:39。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG4恒定区的全长抗LIGHT抗体，其中所述抗LIGHT抗体包含：a)重链可变结构域，所述重链可变结构域包含：HC-CDR1，其包含氨基酸序列SEQ ID NO:3，HC-CDR2，其包含氨基酸序列SEQ ID NO:11，和HC-CDR3，其包含氨基酸序列SEQ ID NO:18；以及b)轻链可变结构域，所述轻链可变结构域包含：LC-CDR1，其包含氨基酸序列SEQ ID NO:26，LC-CDR2，其包含氨基酸序列SEQ ID NO:32，和LC-CDR3，其包含氨基酸序列SEQ ID NO:40。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG4恒定区的全长抗LIGHT抗体，其中所述抗LIGHT抗体包含：a)重链可变结构域，所述重链可变结构域包含：HC-CDR1，其包含氨基酸序列SEQ ID NO:3，HC-CDR2，其包含氨基酸序列SEQ ID NO:11，和HC-CDR3，其包含氨基酸序列SEQ ID NO:18；以及b)轻链可变结构域，所述轻链可变结构域包含：LC-CDR1，其包含氨基酸序列SEQ ID NO:26，LC-CDR2，其包含氨基酸序列SEQ ID NO:32，和LC-CDR3，其包含氨基酸序列SEQ ID NO:41。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。 在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG4恒定区的全长抗LIGHT抗体，其中所述抗LIGHT抗体包含：a)重链可变结构域，所述重链可变结构域包含：HC-CDR1，其包含氨基酸序列SEQ ID NO:4，HC-CDR2，其包含氨基酸序列SEQ ID NO:12，和HC-CDR3，其包含氨基酸序列SEQ ID NO:19；以及b)轻链可变结构域，所述轻链可变结构域包含：LC-CDR1，其包含氨基酸序列SEQ ID NO:27，LC-CDR2，其包含氨基酸序列SEQ ID NO:33，和LC-CDR3，其包含氨基酸序列SEQ ID NO:42。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG4恒定区的全长抗LIGHT抗体，其中所述抗LIGHT抗体包含：a)重链可变结构域，所述重链可变结构域包含：HC-CDR1，其包含氨基酸序列SEQ ID NO:5，HC-CDR2，其包含氨基酸序列SEQ ID NO:13，和HC-CDR3，其包含氨基酸序列SEQ ID NO:20；以及b)轻链可变结构域，所述轻链可变结构域包含：LC-CDR1，其包含氨基酸序列SEQ ID NO:28，LC-CDR2，其包含氨基酸序列SEQ ID NO:34，和LC-CDR3，其包含氨基酸序列SEQ ID NO:43。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG4恒定区的全长抗LIGHT抗体，其中所述抗LIGHT抗体包含：a)重链可变结构域，所述重链可变结构域包含：HC-CDR1，其包含氨基酸序列SEQ ID NO:6，HC-CDR2，其包含氨基酸序列SEQ ID NO:14，和HC-CDR3，其包含氨基酸序列SEQ ID NO:21；以及b)轻链可变结构域，所述轻链可变结构域包含：LC-CDR1，其包含氨基酸序列SEQ ID NO:29，LC-CDR2，其包含氨基酸序列SEQ ID NO:35，和LC-CDR3，其包含氨基酸序列SEQ ID NO:43。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒 定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG4恒定区的全长抗LIGHT抗体，其中所述抗LIGHT抗体包含：a)重链可变结构域，所述重链可变结构域包含：HC-CDR1，其包含氨基酸序列SEQ ID NO:6，HC-CDR2，其包含氨基酸序列SEQ ID NO:14，和HC-CDR3，其包含氨基酸序列SEQ ID NO:21；以及b)轻链可变结构域，所述轻链可变结构域包含：LC-CDR1，其包含氨基酸序列SEQ ID NO:83，LC-CDR2，其包含氨基酸序列SEQ ID NO:35，和LC-CDR3，其包含氨基酸序列SEQ ID NO:43。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG4恒定区的全长抗LIGHT抗体，其中所述抗LIGHT抗体包含：a)重链可变结构域，所述重链可变结构域包含：HC-CDR1，其包含氨基酸序列SEQ ID NO:7，HC-CDR2，其包含氨基酸序列SEQ ID NO:15，和HC-CDR3，其包含氨基酸序列SEQ ID NO:22；以及b)轻链可变结构域，所述轻链可变结构域包含：LC-CDR1，其包含氨基酸序列SEQ ID NO:29，LC-CDR2，其包含氨基酸序列SEQ ID NO:36，和LC-CDR3，其包含氨基酸序列SEQ ID NO:44。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG1恒定区的全长抗LIGHT抗体，其中抗LIGHT抗体包含：重链可变结构域(VH)，所述VH包含SEQ ID NOs:46-61，84-85，92-94中任一所示的氨基酸序列或其变体，所述变体与SEQ ID NOs:46-61，84-85，92-94中任一所示的氨基酸序列具有至少约80％(例如至少80％、85％、90％、95％、96％、97％、98％或99％)序列同一性；以及轻链可变结构域(VL)，所述VL包含SEQ ID NOs:62-73，86-91，95-99中任一所示的氨基酸序列或其变体，所述变体与SEQ ID NOs:62-73，86-91，95-99中任一所示的氨基酸序列具有至少约80％(例如至少80％、85％、90％、95％、96％、97％、98％或99％)序列同一性。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定 区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG2恒定区的全长抗LIGHT抗体，其中抗LIGHT抗体包含：重链可变结构域(VH)，所述VH包含SEQ ID NOs:46-61，84-85，92-94中任一所示的氨基酸序列或其变体，所述变体与SEQ ID NOs:46-61，84-85，92-94中任一所示的氨基酸序列具有至少约80％(例如至少80％、85％、90％、95％、96％、97％、98％或99％)序列同一性；以及轻链可变结构域(VL)，所述VL包含SEQ ID NOs:62-73，86-91，95-99中任一所示的氨基酸序列或其变体，所述变体与SEQ ID NOs:62-73，86-91，95-99中任一所示的氨基酸序列具有至少约80％(例如至少80％、85％、90％、95％、96％、97％、98％或99％)序列同一性。在一些实施例中，所述IgG2是人IgG2。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG3恒定区的全长抗LIGHT抗体，其中抗LIGHT抗体包含：重链可变结构域(VH)，所述VH包含SEQ ID NOs:46-61，84-85，92-94中任一所示的氨基酸序列或其变体，所述变体与SEQ ID NOs:46-61，84-85，92-94中任一所示的氨基酸序列具有至少约80％(例如至少80％、85％、90％、95％、96％、97％、98％或99％)序列同一性；以及轻链可变结构域(VL)，所述VL包含SEQ ID NOs:62-73，86-91，95-99中任一所示的氨基酸序列或其变体，所述变体与SEQ ID NOs:62-73，86-91，95-99中任一所示的氨基酸序列具有至少约80％(例如至少80％、85％、90％、95％、96％、97％、98％或99％)序列同一性。在一些实施例中，所述IgG3是人IgG3。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG4恒定区的全长抗LIGHT抗体，其中抗LIGHT抗体包含：重链可变结构域(VH)，所述VH包含SEQ ID NOs:46-61，84-85，92-94中任一所示的氨基酸序列或其变体，所述变体与SEQ ID NOs:46-61，84-85，92-94中任一所示的氨基酸序列具有至少约80％(例如至少80％、85％、90％、95％、96％、97％、98％或99％)序列同一性；以及轻链可变结构域(VL)，所述VL包含SEQ ID NOs:62-73，86-91，95-99中任一所示的氨基酸序列或其变体，所述变体与SEQ ID NOs:62-73，86-91，95-99中任一所示的氨基酸序列具有至少约80％(例如至少80％、85％、90％、95％、96％、97％、98％或99％)序列同一性。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中， 重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG1恒定区的全长抗LIGHT抗体，其中抗LIGHT抗体包含：重链可变结构域(VH)，所述VH包含SEQ ID NOs:46-61，84-85，92-94中任一所示的氨基酸序列，以及轻链可变结构域(VL)，所述VL包含SEQ ID NOs:62-73，86-91，95-99中任一所示的氨基酸序列。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG4恒定区的全长抗LIGHT抗体，其中抗LIGHT抗体包含：重链可变结构域(VH)，所述VH包含SEQ ID NOs:46-61，84-85，92-94中任一所示的氨基酸序列，以及轻链可变结构域(VL)，所述VL包含SEQ ID NOs:62-73，86-91，95-99中任一所示的氨基酸序列。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG1恒定区的全长抗LIGHT抗体，其中抗LIGHT抗体包含：VH，其包含氨基酸序列SEQ ID NO:46或其变体，所述变体与氨基酸序列SEQ ID NO:46具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:62或其变体，所述变体与氨基酸序列SEQ ID NO:62具有至少约80％序列同一性。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG1恒定区的全长抗LIGHT抗体，其中抗LIGHT抗体包含：VH，其包含氨基酸序列SEQ ID NO:47或其变体，所述变体与氨基酸序列SEQ ID NO:47具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:63或其变体，所述变体与氨基酸序列SEQ ID NO:63具有至少约80％序列同一性。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，轻链恒定区 包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG1恒定区的全长抗LIGHT抗体，其中抗LIGHT抗体包含：VH，其包含氨基酸序列SEQ ID NO:48或其变体，所述变体与氨基酸序列SEQ ID NO:48具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:63或其变体，所述变体与氨基酸序列SEQ ID NO:63具有至少约80％序列同一性。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG1恒定区的全长抗LIGHT抗体，其中抗LIGHT抗体包含：VH，其包含氨基酸序列SEQ ID NO:49或其变体，所述变体与氨基酸序列SEQ ID NO:49具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:63或其变体，所述变体与氨基酸序列SEQ ID NO:63具有至少约80％序列同一性。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG1恒定区的全长抗LIGHT抗体，其中抗LIGHT抗体包含：VH，其包含氨基酸序列SEQ ID NO:50或其变体，所述变体与氨基酸序列SEQ ID NO:50具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:63或其变体，所述变体与氨基酸序列SEQ ID NO:63具有至少约80％序列同一性。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG1恒定区的全长抗LIGHT抗体，其中抗LIGHT抗体包含：VH，其包含氨基酸序列SEQ ID NO:47或其变体，所述变体与氨基酸序列SEQ ID NO:47具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:64或其变体，所述变体与氨基 酸序列SEQ ID NO:64具有至少约80％序列同一性。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG1恒定区的全长抗LIGHT抗体，其中抗LIGHT抗体包含：VH，其包含氨基酸序列SEQ ID NO:48或其变体，所述变体与氨基酸序列SEQ ID NO:48具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:64或其变体，所述变体与氨基酸序列SEQ ID NO:64具有至少约80％序列同一性。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG1恒定区的全长抗LIGHT抗体，其中抗LIGHT抗体包含：VH，其包含氨基酸序列SEQ ID NO:49或其变体，所述变体与氨基酸序列SEQ ID NO:49具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:64或其变体，所述变体与氨基酸序列SEQ ID NO:64具有至少约80％序列同一性。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG1恒定区的全长抗LIGHT抗体，其中抗LIGHT抗体包含：VH，其包含氨基酸序列SEQ ID NO:50或其变体，所述变体与氨基酸序列SEQ ID NO:50具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:64或其变体，所述变体与氨基酸序列SEQ ID NO:64具有至少约80％序列同一性。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG1恒定区的全长抗LIGHT抗体，其中抗LIGHT抗体包含：VH，其包含氨基酸序列SEQ ID NO:47或其变体，所述变体与氨基酸序列SEQ ID NO:47具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:65或其变体，所述变体与氨基酸序列SEQ ID NO:65具有至少约80％序列同一性。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG1恒定区的全长抗LIGHT抗体，其中抗LIGHT抗体包含：VH，其包含氨基酸序列SEQ ID NO:48或其变体，所述变体与氨基酸序列SEQ ID NO:48具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:65或其变体，所述变体与氨基酸序列SEQ ID NO:65具有至少约80％序列同一性。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG1恒定区的全长抗LIGHT抗体，其中抗LIGHT抗体包含：VH，其包含氨基酸序列SEQ ID NO:49或其变体，所述变体与氨基酸序列SEQ ID NO:49具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:65或其变体，所述变体与氨基酸序列SEQ ID NO:65具有至少约80％序列同一性。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG1恒定区的全长抗LIGHT抗体，其中抗LIGHT抗体包含：VH，其包含氨基酸序列SEQ ID NO:50或其变体，所述变体与氨基酸序列SEQ ID NO:50具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:65或其变体，所述变体与氨基酸序列SEQ ID NO:65具有至少约80％序列同一性。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及 轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG1恒定区的全长抗LIGHT抗体，其中抗LIGHT抗体包含：VH，其包含氨基酸序列SEQ ID NO:51或其变体，所述变体与氨基酸序列SEQ ID NO:51具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:63或其变体，所述变体与氨基酸序列SEQ ID NO:63具有至少约80％序列同一性。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG1恒定区的全长抗LIGHT抗体，其中抗LIGHT抗体包含：VH，其包含氨基酸序列SEQ ID NO:52或其变体，所述变体与氨基酸序列SEQ ID NO:52具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:65或其变体，所述变体与氨基酸序列SEQ ID NO:65具有至少约80％序列同一性。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG1恒定区的全长抗LIGHT抗体，其中抗LIGHT抗体包含：VH，其包含氨基酸序列SEQ ID NO:53或其变体，所述变体与氨基酸序列SEQ ID NO:53具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:65或其变体，所述变体与氨基酸序列SEQ ID NO:65具有至少约80％序列同一性。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG1恒定区的全长抗LIGHT抗体，其中抗LIGHT抗体包含：VH，其包含氨基酸序列SEQ ID NO:51或其变体，所述变体与氨基酸序列SEQ ID NO:51具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:65或其变体，所述变体与氨基酸序列SEQ ID NO:65具有至少约80％序列同一性。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，轻链恒定区 包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG1恒定区的全长抗LIGHT抗体，其中抗LIGHT抗体包含：VH，其包含氨基酸序列SEQ ID NO:54或其变体，所述变体与氨基酸序列SEQ ID NO:54具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:66或其变体，所述变体与氨基酸序列SEQ ID NO:66具有至少约80％序列同一性。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG1恒定区的全长抗LIGHT抗体，其中抗LIGHT抗体包含：VH，其包含氨基酸序列SEQ ID NO:55或其变体，所述变体与氨基酸序列SEQ ID NO:55具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:67或其变体，所述变体与氨基酸序列SEQ ID NO:67具有至少约80％序列同一性。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG1恒定区的全长抗LIGHT抗体，其中抗LIGHT抗体包含：VH，其包含氨基酸序列SEQ ID NO:56或其变体，所述变体与氨基酸序列SEQ ID NO:56具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:68或其变体，所述变体与氨基酸序列SEQ ID NO:68具有至少约80％序列同一性。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG1恒定区的全长抗LIGHT抗体，其中抗LIGHT抗体包含：VH，其包含氨基酸序列SEQ ID NO:57或其变体，所述变体与氨基酸序列SEQ ID NO:57具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:69或其变体，所述变体与氨基 酸序列SEQ ID NO:69具有至少约80％序列同一性。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG1恒定区的全长抗LIGHT抗体，其中抗LIGHT抗体包含：VH，其包含氨基酸序列SEQ ID NO:58或其变体，所述变体与氨基酸序列SEQ ID NO:58具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:70或其变体，所述变体与氨基酸序列SEQ ID NO:70具有至少约80％序列同一性。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG1恒定区的全长抗LIGHT抗体，其中抗LIGHT抗体包含：VH，其包含氨基酸序列SEQ ID NO:59或其变体，所述变体与氨基酸序列SEQ ID NO:59具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:71或其变体，所述变体与氨基酸序列SEQ ID NO:71具有至少约80％序列同一性。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG1恒定区的全长抗LIGHT抗体，其中抗LIGHT抗体包含：VH，其包含氨基酸序列SEQ ID NO:60或其变体，所述变体与氨基酸序列SEQ ID NO:60具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:72或其变体，所述变体与氨基酸序列SEQ ID NO:72具有至少约80％序列同一性。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG1恒定区的全长抗LIGHT抗体，其中抗LIGHT抗体包含：VH，其包含氨基酸序列SEQ ID NO:84或其变体，所述变体与氨基酸序列SEQ ID NO:84具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:86或其变体，所述变体与氨基酸序列SEQ ID NO:86具有至少约80％序列同一性。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG1恒定区的全长抗LIGHT抗体，其中抗LIGHT抗体包含：VH，其包含氨基酸序列SEQ ID NO:85或其变体，所述变体与氨基酸序列SEQ ID NO:85具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:87或其变体，所述变体与氨基酸序列SEQ ID NO:87具有至少约80％序列同一性。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG1恒定区的全长抗LIGHT抗体，其中抗LIGHT抗体包含：VH，其包含氨基酸序列SEQ ID NO:84或其变体，所述变体与氨基酸序列SEQ ID NO:84具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:88或其变体，所述变体与氨基酸序列SEQ ID NO:88具有至少约80％序列同一性。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG1恒定区的全长抗LIGHT抗体，其中抗LIGHT抗体包含：VH，其包含氨基酸序列SEQ ID NO:84或其变体，所述变体与氨基酸序列SEQ ID NO:84具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:89或其变体，所述变体与氨基酸序列SEQ ID NO:89具有至少约80％序列同一性。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及 轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG1恒定区的全长抗LIGHT抗体，其中抗LIGHT抗体包含：VH，其包含氨基酸序列SEQ ID NO:85或其变体，所述变体与氨基酸序列SEQ ID NO:85具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:90或其变体，所述变体与氨基酸序列SEQ ID NO:90具有至少约80％序列同一性。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG1恒定区的全长抗LIGHT抗体，其中抗LIGHT抗体包含：VH，其包含氨基酸序列SEQ ID NO:84或其变体，所述变体与氨基酸序列SEQ ID NO:84具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:91或其变体，所述变体与氨基酸序列SEQ ID NO:91具有至少约80％序列同一性。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG1恒定区的全长抗LIGHT抗体，其中抗LIGHT抗体包含：VH，其包含氨基酸序列SEQ ID NO:61或其变体，所述变体与氨基酸序列SEQ ID NO:61具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:73或其变体，所述变体与氨基酸序列SEQ ID NO:73具有至少约80％序列同一性。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG1恒定区的全长抗LIGHT抗体，其中抗LIGHT抗体包含：VH，其包含氨基酸序列SEQ ID NO:92或其变体，所述变体与氨基酸序列SEQ ID NO:92具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:95或其变体，所述变体与氨基酸序列SEQ ID NO:95具有至少约80％序列同一性。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，轻链恒定区 包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG1恒定区的全长抗LIGHT抗体，其中抗LIGHT抗体包含：VH，其包含氨基酸序列SEQ ID NO:93或其变体，所述变体与氨基酸序列SEQ ID NO:93具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:96或其变体，所述变体与氨基酸序列SEQ ID NO:96具有至少约80％序列同一性。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG1恒定区的全长抗LIGHT抗体，其中抗LIGHT抗体包含：VH，其包含氨基酸序列SEQ ID NO:92或其变体，所述变体与氨基酸序列SEQ ID NO:92具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:96或其变体，所述变体与氨基酸序列SEQ ID NO:96具有至少约80％序列同一性。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG1恒定区的全长抗LIGHT抗体，其中抗LIGHT抗体包含：VH，其包含氨基酸序列SEQ ID NO:94或其变体，所述变体与氨基酸序列SEQ ID NO:94具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:97或其变体，所述变体与氨基酸序列SEQ ID NO:97具有至少约80％序列同一性。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG1恒定区的全长抗LIGHT抗体，其中抗LIGHT抗体包含：VH，其包含氨基酸序列SEQ ID NO:94或其变体，所述变体与氨基酸序列SEQ ID NO:94具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:98或其变体，所述变体与氨基 酸序列SEQ ID NO:98具有至少约80％序列同一性。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG1恒定区的全长抗LIGHT抗体，其中抗LIGHT抗体包含：VH，其包含氨基酸序列SEQ ID NO:93或其变体，所述变体与氨基酸序列SEQ ID NO:93具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:98或其变体，所述变体与氨基酸序列SEQ ID NO:98具有至少约80％序列同一性。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG1恒定区的全长抗LIGHT抗体，其中抗LIGHT抗体包含：VH，其包含氨基酸序列SEQ ID NO:92或其变体，所述变体与氨基酸序列SEQ ID NO:92具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:98或其变体，所述变体与氨基酸序列SEQ ID NO:98具有至少约80％序列同一性。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG1恒定区的全长抗LIGHT抗体，其中抗LIGHT抗体包含：VH，其包含氨基酸序列SEQ ID NO:94或其变体，所述变体与氨基酸序列SEQ ID NO:94具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:99或其变体，所述变体与氨基酸序列SEQ ID NO:99具有至少约80％序列同一性。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG1恒定区的全长抗LIGHT抗体，其中抗LIGHT抗体包含：VH，其包含氨基酸序列SEQ ID NO:92或其变体，所述变体与氨基酸序列SEQ ID NO:92具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:99或其变体，所述变体与氨基酸序列SEQ ID NO:99具有至少约80％序列同一性。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG4恒定区的全长抗LIGHT抗体，其中抗LIGHT抗体包含：VH，其包含氨基酸序列SEQ ID NO:46或其变体，所述变体与氨基酸序列SEQ ID NO:46具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:62或其变体，所述变体与氨基酸序列SEQ ID NO:62具有至少约80％序列同一性。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG4恒定区的全长抗LIGHT抗体，其中抗LIGHT抗体包含：VH，其包含氨基酸序列SEQ ID NO:47或其变体，所述变体与氨基酸序列SEQ ID NO:47具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:63或其变体，所述变体与氨基酸序列SEQ ID NO:63具有至少约80％序列同一性。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG4恒定区的全长抗LIGHT抗体，其中抗LIGHT抗体包含：VH，其包含氨基酸序列SEQ ID NO:48或其变体，所述变体与氨基酸序列SEQ ID NO:48具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:63或其变体，所述变体与氨基酸序列SEQ ID NO:63具有至少约80％序列同一性。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及 轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG4恒定区的全长抗LIGHT抗体，其中抗LIGHT抗体包含：VH，其包含氨基酸序列SEQ ID NO:49或其变体，所述变体与氨基酸序列SEQ ID NO:49具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:63或其变体，所述变体与氨基酸序列SEQ ID NO:63具有至少约80％序列同一性。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG4恒定区的全长抗LIGHT抗体，其中抗LIGHT抗体包含：VH，其包含氨基酸序列SEQ ID NO:50或其变体，所述变体与氨基酸序列SEQ ID NO:50具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:63或其变体，所述变体与氨基酸序列SEQ ID NO:63具有至少约80％序列同一性。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG4恒定区的全长抗LIGHT抗体，其中抗LIGHT抗体包含：VH，其包含氨基酸序列SEQ ID NO:47或其变体，所述变体与氨基酸序列SEQ ID NO:47具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:64或其变体，所述变体与氨基酸序列SEQ ID NO:64具有至少约80％序列同一性。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG4恒定区的全长抗LIGHT抗体，其中抗LIGHT抗体包含：VH，其包含氨基酸序列SEQ ID NO:48或其变体，所述变体与氨基酸序列SEQ ID NO:48具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:64或其变体，所述变体与氨基酸序列SEQ ID NO:64具有至少约80％序列同一性。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区 包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG4恒定区的全长抗LIGHT抗体，其中抗LIGHT抗体包含：VH，其包含氨基酸序列SEQ ID NO:49或其变体，所述变体与氨基酸序列SEQ ID NO:49具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:64或其变体，所述变体与氨基酸序列SEQ ID NO:64具有至少约80％序列同一性。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG4恒定区的全长抗LIGHT抗体，其中抗LIGHT抗体包含：VH，其包含氨基酸序列SEQ ID NO:50或其变体，所述变体与氨基酸序列SEQ ID NO:50具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:64或其变体，所述变体与氨基酸序列SEQ ID NO:64具有至少约80％序列同一性。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG4恒定区的全长抗LIGHT抗体，其中抗LIGHT抗体包含：VH，其包含氨基酸序列SEQ ID NO:47或其变体，所述变体与氨基酸序列SEQ ID NO:47具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:65或其变体，所述变体与氨基酸序列SEQ ID NO:65具有至少约80％序列同一性。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG4恒定区的全长抗LIGHT抗体，其中抗LIGHT抗体包含：VH，其包含氨基酸序列SEQ ID NO:48或其变体，所述变体与氨基酸序列SEQ ID NO:48具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:65或其变体，所述变体与氨基 酸序列SEQ ID NO:65具有至少约80％序列同一性。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG4恒定区的全长抗LIGHT抗体，其中抗LIGHT抗体包含：VH，其包含氨基酸序列SEQ ID NO:49或其变体，所述变体与氨基酸序列SEQ ID NO:49具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:65或其变体，所述变体与氨基酸序列SEQ ID NO:65具有至少约80％序列同一性。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG4恒定区的全长抗LIGHT抗体，其中抗LIGHT抗体包含：VH，其包含氨基酸序列SEQ ID NO:50或其变体，所述变体与氨基酸序列SEQ ID NO:50具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:65或其变体，所述变体与氨基酸序列SEQ ID NO:65具有至少约80％序列同一性。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG4恒定区的全长抗LIGHT抗体，其中抗LIGHT抗体包含：VH，其包含氨基酸序列SEQ ID NO:51或其变体，所述变体与氨基酸序列SEQ ID NO:51具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:63或其变体，所述变体与氨基酸序列SEQ ID NO:63具有至少约80％序列同一性。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG4恒定区的全长抗LIGHT抗体，其中抗LIGHT抗体包含：VH，其包含氨基酸序列SEQ ID NO:52或其变体，所述变体与氨基酸序列SEQ ID NO:52具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:65或其变体，所述变体与氨基酸序列SEQ ID NO:65具有至少约80％序列同一性。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG4恒定区的全长抗LIGHT抗体，其中抗LIGHT抗体包含：VH，其包含氨基酸序列SEQ ID NO:53或其变体，所述变体与氨基酸序列SEQ ID NO:53具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:65或其变体，所述变体与氨基酸序列SEQ ID NO:65具有至少约80％序列同一性。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG4恒定区的全长抗LIGHT抗体，其中抗LIGHT抗体包含：VH，其包含氨基酸序列SEQ ID NO:51或其变体，所述变体与氨基酸序列SEQ ID NO:51具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:65或其变体，所述变体与氨基酸序列SEQ ID NO:65具有至少约80％序列同一性。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG4恒定区的全长抗LIGHT抗体，其中抗LIGHT抗体包含：VH，其包含氨基酸序列SEQ ID NO:54或其变体，所述变体与氨基酸序列SEQ ID NO:54具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:66或其变体，所述变体与氨基酸序列SEQ ID NO:66具有至少约80％序列同一性。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及 轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG4恒定区的全长抗LIGHT抗体，其中抗LIGHT抗体包含：VH，其包含氨基酸序列SEQ ID NO:55或其变体，所述变体与氨基酸序列SEQ ID NO:55具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:67或其变体，所述变体与氨基酸序列SEQ ID NO:67具有至少约80％序列同一性。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG4恒定区的全长抗LIGHT抗体，其中抗LIGHT抗体包含：VH，其包含氨基酸序列SEQ ID NO:56或其变体，所述变体与氨基酸序列SEQ ID NO:56具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:68或其变体，所述变体与氨基酸序列SEQ ID NO:68具有至少约80％序列同一性。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG4恒定区的全长抗LIGHT抗体，其中抗LIGHT抗体包含：VH，其包含氨基酸序列SEQ ID NO:57或其变体，所述变体与氨基酸序列SEQ ID NO:57具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:69或其变体，所述变体与氨基酸序列SEQ ID NO:69具有至少约80％序列同一性。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG4恒定区的全长抗LIGHT抗体，其中抗LIGHT抗体包含：VH，其包含氨基酸序列SEQ ID NO:58或其变体，所述变体与氨基酸序列SEQ ID NO:58具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:70或其变体，所述变体与氨基酸序列SEQ ID NO:70具有至少约80％序列同一性。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区 包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG4恒定区的全长抗LIGHT抗体，其中抗LIGHT抗体包含：VH，其包含氨基酸序列SEQ ID NO:59或其变体，所述变体与氨基酸序列SEQ ID NO:59具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:71或其变体，所述变体与氨基酸序列SEQ ID NO:71具有至少约80％序列同一性。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG4恒定区的全长抗LIGHT抗体，其中抗LIGHT抗体包含：VH，其包含氨基酸序列SEQ ID NO:60或其变体，所述变体与氨基酸序列SEQ ID NO:60具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:72或其变体，所述变体与氨基酸序列SEQ ID NO:72具有至少约80％序列同一性。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG4恒定区的全长抗LIGHT抗体，其中抗LIGHT抗体包含：VH，其包含氨基酸序列SEQ ID NO:84或其变体，所述变体与氨基酸序列SEQ ID NO:84具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:86或其变体，所述变体与氨基酸序列SEQ ID NO:86具有至少约80％序列同一性。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG4恒定区的全长抗LIGHT抗体，其中抗LIGHT抗体包含：VH，其包含氨基酸序列SEQ ID NO:85或其变体，所述变体与氨基酸序列SEQ ID NO:85具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:87或其变体，所述变体与氨基 酸序列SEQ ID NO:87具有至少约80％序列同一性。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG4恒定区的全长抗LIGHT抗体，其中抗LIGHT抗体包含：VH，其包含氨基酸序列SEQ ID NO:84或其变体，所述变体与氨基酸序列SEQ ID NO:84具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:88或其变体，所述变体与氨基酸序列SEQ ID NO:88具有至少约80％序列同一性。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG4恒定区的全长抗LIGHT抗体，其中抗LIGHT抗体包含：VH，其包含氨基酸序列SEQ ID NO:84或其变体，所述变体与氨基酸序列SEQ ID NO:84具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:89或其变体，所述变体与氨基酸序列SEQ ID NO:89具有至少约80％序列同一性。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG4恒定区的全长抗LIGHT抗体，其中抗LIGHT抗体包含：VH，其包含氨基酸序列SEQ ID NO:85或其变体，所述变体与氨基酸序列SEQ ID NO:85具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:90或其变体，所述变体与氨基酸序列SEQ ID NO:90具有至少约80％序列同一性。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG4恒定区的全长抗LIGHT抗体，其中抗LIGHT抗体包含：VH，其包含氨基酸序列SEQ ID NO:84或其变体，所述变体与氨基酸序列SEQ ID NO:84具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:91或其变体，所述变体与氨基酸序列SEQ ID NO:91具有至少约80％序列同一性。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG4恒定区的全长抗LIGHT抗体，其中抗LIGHT抗体包含：VH，其包含氨基酸序列SEQ ID NO:61或其变体，所述变体与氨基酸序列SEQ ID NO:61具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:73或其变体，所述变体与氨基酸序列SEQ ID NO:73具有至少约80％序列同一性。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG4恒定区的全长抗LIGHT抗体，其中抗LIGHT抗体包含：VH，其包含氨基酸序列SEQ ID NO:92或其变体，所述变体与氨基酸序列SEQ ID NO:92具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:95或其变体，所述变体与氨基酸序列SEQ ID NO:95具有至少约80％序列同一性。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG4恒定区的全长抗LIGHT抗体，其中抗LIGHT抗体包含：VH，其包含氨基酸序列SEQ ID NO:93或其变体，所述变体与氨基酸序列SEQ ID NO:93具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:96或其变体，所述变体与氨基酸序列SEQ ID NO:96具有至少约80％序列同一性。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及 轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG4恒定区的全长抗LIGHT抗体，其中抗LIGHT抗体包含：VH，其包含氨基酸序列SEQ ID NO:92或其变体，所述变体与氨基酸序列SEQ ID NO:92具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:96或其变体，所述变体与氨基酸序列SEQ ID NO:96具有至少约80％序列同一性。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG4恒定区的全长抗LIGHT抗体，其中抗LIGHT抗体包含：VH，其包含氨基酸序列SEQ ID NO:94或其变体，所述变体与氨基酸序列SEQ ID NO:94具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:97或其变体，所述变体与氨基酸序列SEQ ID NO:97具有至少约80％序列同一性。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG4恒定区的全长抗LIGHT抗体，其中抗LIGHT抗体包含：VH，其包含氨基酸序列SEQ ID NO:94或其变体，所述变体与氨基酸序列SEQ ID NO:94具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:98或其变体，所述变体与氨基酸序列SEQ ID NO:98具有至少约80％序列同一性。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG4恒定区的全长抗LIGHT抗体，其中抗LIGHT抗体包含：VH，其包含氨基酸序列SEQ ID NO:93或其变体，所述变体与氨基酸序列SEQ ID NO:93具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:98或其变体，所述变体与氨基酸序列SEQ ID NO:98具有至少约80％序列同一性。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区 包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG4恒定区的全长抗LIGHT抗体，其中抗LIGHT抗体包含：VH，其包含氨基酸序列SEQ ID NO:92或其变体，所述变体与氨基酸序列SEQ ID NO:92具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:98或其变体，所述变体与氨基酸序列SEQ ID NO:98具有至少约80％序列同一性。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG4恒定区的全长抗LIGHT抗体，其中抗LIGHT抗体包含：VH，其包含氨基酸序列SEQ ID NO:94或其变体，所述变体与氨基酸序列SEQ ID NO:94具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:99或其变体，所述变体与氨基酸序列SEQ ID NO:99具有至少约80％序列同一性。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种包含IgG4恒定区的全长抗LIGHT抗体，其中抗LIGHT抗体包含：VH，其包含氨基酸序列SEQ ID NO:92或其变体，所述变体与氨基酸序列SEQ ID NO:92具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:99或其变体，所述变体与氨基酸序列SEQ ID NO:99具有至少约80％序列同一性。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成以及轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
结合亲和力
结合亲和力采用Kd、Koff、Kon或Ka表示。如本文所用，术语Koff是指抗体从抗原/抗体复合物中解离的速率常数，通过动力学选择装置测定。术语Kon是指抗体与抗原结合形成抗原/抗体 复合物的结合速率常数。本文所用的平衡解离常数Kd是指特定抗体抗原相互作用时的解离常数，是指在抗体分子溶液中，抗原占据所有抗体结合位点的一半并且达到平衡时所需的抗原浓度，等于Koff/Kon。Kd的测定假设所有的结合分子均在溶液中。抗体与细胞壁连接的情况，例如在酵母表达系统中，相应的平衡解离速率常数采用EC50来表示，其是Kd的一个良好的近似值。亲和结合常数Ka是解离常数Kd的倒数。
解离常数(Kd)可以作为反应抗体部分与抗原亲和力的指标。例如，可以通过Scatchard方法使用标记有各种标记物的抗体，和Biacore仪器(由Amersham Biosciences制造)进行简单分析，根据用户手册或附带试剂盒，通过表面等离子体共振来分析生物分子间的相互作用。使用这些方法得到的Kd值，用单位M来表示。与靶标特异性结合的抗体可能具有，例如≤10-7M、≤10-8M、≤10-9M、≤10-10M、≤10-11M、≤10-12M或≤10-13M的Kd值。
抗体的结合特异性可以通过本领域已知的方法进行实验测定。这些方法包括，但不限于Western blots、ELISA-、RIA-、ECL-、IRMA-、EIA-、BIAcore测试和肽扫描等。
在一些实施例中，所述抗LIGHT抗体特异性结合LIGHT靶标，其Kd值为10-7M至10-13M(例如10-7M至10-13M、10-8M至10-13M、10-9M至10-13M或10-10M至10-12M)。因此，在一些实施例中，抗LIGHT抗体与LIGHT之间结合的Kd值为10-7M至10-13M、1×10-7M至5×10- 13M、10-7M至10-12M、10-7M至10-11M、10-7M至10-10M、10-7M至10-9M、10-8M至10- 13M、1×10-8M至5×10-13M、10-8M至10-12M、10-8M至10-11M、10-8M至10-10M、10-8M至10-9M、5×10-9M至1×10-13M、5×10-9M至1×10-12M、5×10-9M至1×10-11M、5×10-9M至1×10- 10M、10-9M至10-13M、10-9M至10-12M、10-9M至10-11M、10-9M至10-10M、5×10-10M至1×10-13M、5×10-10M至1×10-12M、5×10-10M至1×10-11M、10-10M至10-13M、1×10-10M至5×10- 13M、1×10-10M至1×10-12M、1×10-10M至5×10-12M、1×10-10M至1×10-11M、10-11M至10- 13M、1×10-11M至5×10-13M、10-11M至10-12M、10-12M至10-13M。在一些实施例中，抗LIGHT抗体与LIGHT之间结合的Kd值为10-7M至10-13M。
在一些实施例中，抗LIGHT抗体与非靶标之间结合的Kd值高于抗LIGHT抗体与靶标的Kd值，并且本文中引用的一些实施例中，抗LIGHT抗体与靶标(例如，LIGHT)的结合亲和力高于抗LIGHT抗体与非靶标的结合亲和力。一些实施例中，非靶标是指非LIGHT的抗原。在一些实施例中，抗LIGHT抗体(针对LIGHT)与非LIGHT靶标结合的Kd值间至少相差10倍，例如10-100倍、100-1000倍、103-104倍、104-105倍、105-106倍、106-107倍、107-108倍、108-109倍、109-1010倍、1010-1011倍、1011-1012倍。
在一些实施例中，所述抗LIGHT抗体与非靶标结合的Kd值为10-1M至10-6M(例如10-1M至10-6M、10-1M至10-5M、10-2M至10-4M)。在一些实施例中，所述非靶标是指非LIGHT的抗原。因此，在一些实施例中，抗LIGHT抗体与非LIGHT靶标之间结合的Kd值为10-1M至10-6M、1×10-1M至5×10-6M、10-1M至10-5M、1×10-1M至5×10-5M、10-1M至10-4M、1×10-1M至5×10-4M、10-1M至10-3M、1×10-1M至5×10-3M、10-1M至10-2M、10-2M至10-6M、1×10-2M 至5×10-6M、10-2M至10-5M、1×10-2M至5×10-5M、10-2M至10-4M、1×10-2M至5×10-4M、10- 2M至10-3M、10-3M至10-6M、1×10-3M至5×10-6M、10-3M至10-5M、1×10-3M至5×10-5M、10-3M至10-4M、10-4M至10-6M、1×10-4M至5×10-6M、10-4M至10-5M、10-5M至10-6M。
在一些实施例中，当提及抗LIGHT抗体以高结合亲和力特异性地识别LIGHT靶标，并以低结合亲和力结合非靶标时，所述抗LIGHT抗体与LIGHT靶标结合的Kd值为10-7M至10-13M(例如10-7M至10-13M、10-8M至10-13M、10-9M至10-13M、10-10M至10-12M)，并且与非靶标结合的Kd值为10-1M至10-6M(例如10-1M至10-6M、10-1M至10-5M、10-2M至10-4M)。
在一些实施例中，当提及抗LIGHT抗体特异性地识别LIGHT时，将所述抗LIGHT抗体的结合亲和力与对照抗LIGHT抗体(例如CERC-002)的结合亲和力进行比较。在一些实施例中，对照抗LIGHT抗体与LIGHT之间结合的Kd值可以是本申请所述的抗LIGHT抗体与LIGHT之间结合的Kd值的至少2倍，例如2倍、3倍、4倍、5倍、6倍、7倍、8倍、9倍、10倍、10-100倍、100-1000倍、103-104倍。
核酸
编码抗LIGHT抗体的核酸分子也被考虑在内。在一些实施例中，提供一种(或一组)编码全长抗LIGHT抗体的核酸，包括本文所述的任一种全长抗LIGHT抗体。在一些实施例中，本文所述的抗LIGHT抗体的核酸(或一组核酸)还可以包括编码多肽标签的核酸序列(例如蛋白纯化标签，His标签、HA标签)。
同时本文还考虑了包含抗LIGHT抗体的分离的宿主细胞，编码抗LIGHT抗体多肽组分的分离的核酸，或者包含编码本文所述的抗LIGHT抗体多肽组分的核酸的载体。
本申请还包括这些核酸序列的变体。例如，变体包括至少在中等严格杂交条件下与编码本申请的抗LIGHT抗体的核酸序列杂交的核苷酸序列。
本申请同时还提供可将本申请中核酸序列插入到其中的载体。
简言之，将编码抗LIGHT抗体的天然或合成的核酸插入到合适的表达载体中，使得核酸可操作性的连接到5’和3’端调控元件，例如包括启动子(例如淋巴细胞特异性启动子)和3’非翻译区(UTR)，可表达抗LIGHT抗体(例如全长的抗LIGHT抗体)。所述载体可适用于在真核宿主细胞中复制和整合。典型的克隆与表达载体包含调控目标核酸序列的表达的转录和翻译终止子、起始序列和启动子。
本申请所述的核酸也可以通过使用标准的基因递送方案，用于核酸免疫和基因治疗。核酸递送方法是本领域已知的。例如参见U.S.Pat.Nos.5,399,346、5,580,859、5,589,466，通过引用其全部内容并入本文。在一些实施例中，本申请还提供基因治疗载体。
可以将核酸克隆到许多类型的载体中。例如，可以将核酸克隆到载体中，所述载体包括，但不限于，质粒、噬菌粒、噬菌体衍生物、动物病毒和柯斯质粒。特别感兴趣的载体包括表达载体、复制载体、探针生成载体和测序载体。
此外，表达载体可以以病毒载体的形式提供给细胞。病毒载体技术是本领域熟知的，并且描述于例如Green and Sambrook(2013,Molecular Cloning:A Laboratory Manual,Cold Spring Harbor Laboratory,New York)，以及其它病毒学或分子生物学手册中。可用作载体的病毒包括，但不限于，逆转录病毒、腺病毒、腺相关病毒、疱疹病毒和慢病毒。通常，合适的载体包括一个在至少一种生物体中起作用的复制起点、启动子序列、方便的限制性内切酶位点以及一个或多个选择标记物(参见例如，WO 01/96584；WO 01/29058；和U.S.Pat.No.6,326,193)。
已经开发了许多基于病毒的系统，用于将基因转移到哺乳动物细胞中。例如，逆转录病毒为基因递送系统提供了便利的平台。可以应用本领域已知的技术，将选择的基因插入载体中并包装在逆转录病毒颗粒中。然后分离重组病毒，在体内或体外递送至受试者的细胞中。许多逆转录病毒系统在本领域中是已知的。在一些实施例中，使用腺病毒载体。许多腺病毒载体在本领域中是已知的。在一些实施例中，使用慢病毒载体。衍生自逆转录病毒的载体，例如慢病毒，是实现长期基因转移的合适工具，因为它们使得转基因长期稳定的整合以及在子代细胞中繁殖。慢病毒载体相对于衍生自肿瘤的逆转录病毒例如小鼠白血病病毒具有额外的优势，因为它们可以转导非分裂细胞，例如肝细胞。同时，其还具有低免疫原性的额外优势。
其它的启动子元件，例如，增强子，调控转录起始频率。通常它们位于起始位点上游30-110bp处，虽然最近发现很多启动子也包含起始位点下游的功能元件。启动子元件之间的间隔通常是灵活的，所以当元件彼此之间位置互换或移动时仍保持启动子的功能。在胸苷激酶(tk)启动子中，启动子元件之间的间隔增加到50bp活性才会开始下降。
合适启动子的一个示例是即时早期巨细胞病毒(CMV)启动子序列。该启动子序列是一个很强的组成型启动子序列，可以驱动任何与其可操作性连接的多核苷酸序列高水平表达。合适启动子的另一个示例是延伸因子1α(EF-1α)启动子。然而，也可以使用其它组成型启动子，包括但不限于猿猴病毒40(SV40)早期启动子、小鼠乳腺肿瘤病毒(MMTV)、人免病缺陷病毒长末端重复序列(HIV-LTR)启动子、MoMuLV启动子、禽类白血病病毒启动子、Epstein-Barr病毒即刻早期启动子、劳斯氏肉瘤病毒启动子以及人类基因启动子，例如包括但不限于肌动蛋白启动子、肌球蛋白启动子、血红蛋白启动子和肌酸激酶启动子。此外，不应将本申请局限在仅使用组成型启动子，诱导型启动子也是本申请考虑的部分。诱导型启动子的使用提供了一种分子开关，当需要这种表达时，能启动其与之可操作性连接的多核苷酸序列表达，当不需要时，则关闭表达。诱导型启动子包含，但不局限于，金属硫蛋白启动子、糖皮质激素启动子、孕酮启动子和四环素启动子。
在一些实施例中，抗LIGHT抗体的表达是可诱导的。在一些实施例中，编码抗LIGHT抗体的核酸序列可操作的连接到诱导型启动子上，包括本文所述的任一诱导型启动子。
诱导型启动子
诱导型启动子的使用提供了一种分子开关，当需要表达时，可启动与之可操作性连接的多核苷酸序列表达，而在不需要表达时，则关闭表达。真核细胞中适用的示例性诱导型启动子包括， 但不限于，激素调节元件(例如，参见Mader,S.and White,J.H.(1993)Proc.Natl.Acad.Sci.USA 90:5603-5607)、合成配体调节元件(参见Spencer,D.M.et al(1993)Science 262:1019-1024)以及电离辐射调控元件(参见Manome,Y.et al.(1993)Biochemistry 32:10607-10613；Datta,R.et al.(1992)Proc.Natl.Acad.Sci.USA 89:1014-10153)。其它适用于体内或体外哺乳动物系统的示例性诱导型启动子参见Gingrich et al.(1998)Annual Rev.Neurosci 21:377-405。在一些实施例中，用于表达抗LIGHT抗体的诱导型启动子系统为Tet系统。在一些实施例中，用于表达抗LIGHT抗体的诱导型启动子系统为大肠杆菌lac抑制系统。
本申请所采用的一个示例性诱导型启动子系统为Tet系统。该系统是基于Gossen等(1993)描述的Tet系统。在一个示例性实施例中，目标多核苷酸由包含一个或多个Tet操纵子(TetO)位点的启动子控制。在非激活状态，Tet阻遏物(TetR)与TetO位点结合并抑制启动子的转录。在激活状态，例如，在存在诱导剂如四环素(Tc)、无水四环素、多西环素(Dox)或其活性类似物的情况下，诱导剂会使TetR从TetO上释放，从而导致转录发生。多西环素是四环素抗生素家族中的一员，其化学名为1-二甲氨基-2,4a,5,7-五羟基-11-甲基-4,6-二氧基-1,4a,11,11a,12,12a-六氢四烯-3-甲酰胺。
在一个实施例中，TetR经密码子优化适用于在哺乳动物细胞中表达，例如小鼠或人类细胞。由于遗传密码的简并性，大多数氨基酸由不止一个密码子编码，从而使得给定核酸的序列具有大量的变体，而其编码的氨基酸序列没有任何改变。然而，许多生物体在密码子使用方面存在差异，也称为“密码子偏好”(即，给定氨基酸使用特定密码子的偏好)。密码子偏好通常与特定密码子的优势tRNA种类的存在有关，反过来又提高了mRNA翻译的效率。因此可以通过密码子优化来定制源自特定物种的编码序列(例如，原核生物)，以提高其在不同物种(例如，真核生物)中的表达。
Tet系统的其它具体变体，包括以下的“Tet-Off”和“Tet-On”系统。在Tet-off系统中，转录在Tc或Dox存在下是失活的。在该系统中，由TetR与单纯疱疹病毒VP16强转录激活结构域融合组成的四环素调控的转录激活蛋白(tTA)，在四环素反应启动子元件(TRE)转录控制下调控靶核酸的表达。TRE元件由TetO序列串联与启动子(通常是来源于人巨细胞病毒即刻早期启动子的最小启动子序列)融合组成。在不存在Tc或Dox的情况下，tTA结合TRE并激活靶基因的转录。在存在Tc或Dox的情况下，tTA不能结合TRE，靶基因不能表达。
相反，在Tet-On系统中，转录在Tc或Dox存在下是激活的。Tet-On系统是基于反向四环素调控的转录激活因子rtTA。与tTA一样，rtTA是由TetR阻遏物与VP16转录激活结构域组成的融合蛋白。然而，TetR的DNA结合区中4个氨基酸的变化改变了rtTA的结合特性，使其在存在Dox的情况下只能识别靶转基因TRE上的tetO序列。所以在Tet-On系统中，只有在存在Dox的情况下，rtTA才能激活TRE调控的靶基因的转录。
另一种诱导型启动子系统是大肠杆菌的lac阻遏物系统(参见Brown et al.,Cell 49:603-612(1987))。Lac阻遏物系统通过调控与包含lac操纵子(lacO)的启动子可操作性连接的目标多 核苷酸的转录发挥功能。Lac阻遏物(lacR)与LacO结合，进而阻止目标多核苷酸的转录。通过合适的诱导剂来诱导目标多核苷酸的表达，例如，异丙基-β-D硫代半乳糖吡喃苷(IPTG)。
为了评估多肽或其部分的表达，待导入细胞的表达载体还可包含选择标记基因或报告基因或二者都有，以便于从病毒载体转染或感染的细胞群体中识别和选择表达细胞。在其他方面，选择标记可以携带在单独的DNA片段上并在共转染实验中使用。选择标记基因或报告基因都可侧接于合适的调控序列，使其在宿主细胞中能够表达。有用的选择标记包括，例如，抗生素耐药基因，如neo以及类似基因。
报告基因可用于鉴定潜在的转染细胞和评价调控序列的功能。通常，报告基因是不存在于受体生物体或组织中或不由受体生物体或组织表达的基因，其编码一种多肽，其表达表现为一些易于检测的特性，例如酶活性。当DNA导入受体细胞后，在合适的时间检测报告基因的表达。合适的报告基因可包括编码荧光素酶、β-半乳糖苷酶、氯霉素乙酰转移酶、分泌碱性磷酸酶或绿色荧光蛋白的基因(参见,Ui-Tel et al.,2000 FEBS Letters 479:79-82)。合适的表达系统是公知的，可以通过已知的技术制备或通过商业途径获得。通常，把可显示报告基因最高表达水平的最小5’侧翼区的构建体认定为启动子。此类启动子区可以与报告基因连接，并用于评估某些物质在调节启动子驱动的转录中能力。
在一些实施例中，提供编码本文所述的任一种全长抗LIGHT抗体的核酸。在一些实施例中，所述核酸包括编码全长抗LIGHT抗体重链和轻链的一个或多个核酸序列。在一些实施例中，所述一个或多个核酸序列中的每一个包含在单独的载体中。在一些实施例中，至少有一些核酸序列包含在同一载体中。在一些实施例中，所有核酸序列包含在同一载体中。载体可以选自，例如，哺乳动物表达载体和病毒载体(如源自逆转录病毒、腺病毒、腺相关病毒、疱疹病毒和慢病毒的载体)。
将基因导入细胞并表达的方法在本领域是已知的。在涉及表达载体的上下文中，通过本领域的任何方法载体可以很容易地导入宿主细胞中，如哺乳动物细胞、细菌、酵母或昆虫细胞。例如表达载体可以通过物理、化学或生物方法导入宿主细胞。
将多核苷酸导入宿主细胞的物理方法包括磷酸钙沉淀、脂质体转染、基因枪法、显微注射、电穿孔法以及诸如此类。制备包含载体和/或外源核酸的细胞的方法在本领域是熟知的。参见例如Green and Sambrook(2013,Molecular Cloning:A Laboratory Manual,Cold Spring Harbor Laboratory,New York)。在一些实施例中，通过磷酸钙转染法将多核苷酸导入宿主细胞。
将目标多核苷酸导入宿主细胞的生物学方法包括使用DNA和RNA载体。病毒载体，特别是逆转录病毒载体，已成为将基因插入哺乳动物细胞，例如人类细胞中的最广泛使用的方法。其它病毒载体可以源自慢病毒、痘病毒、单纯疱疹病毒1型、腺病毒和腺相关病毒等。参见如U.S.Pat.Nos.5,350,674和5,585,362。
将多核苷酸导入宿主细胞的化学方法包括胶体分散系统，例如高分子复合物、纳米胶囊、微球、磁珠和以脂质为基础的系统，其包括水包油乳剂、胶团、混合胶团和脂质体。一种在体内和体外被用作递送载体的示例性胶体系统是脂质体(例如，人工膜囊)。
在使用非病毒递送系统的情况下，示例性的递送载体是脂质体。考虑使用脂质制剂将核酸导入宿主细胞(体外、离体或体内)。在另一方面，所述核酸可以与脂质结合。与脂质结合的核酸可被包裹进脂质体的水性内部，散布在脂质体的脂质双层内，通过与脂质体和寡核苷酸结合的连接分子连接在脂质体，包埋在脂质体中，与脂质体形成复合物，分散在含有脂质的溶液中，与脂质混合，与脂质结合，悬浮在脂质中，包含在胶束中或与胶束混合，或以其它方式与脂质结合。脂质、脂质/DNA或脂质/表达载体相关的组合物在溶液中不限于任何特定结构。例如，它们可能以双分子层结构、以胶束或以“塌陷”结构存在。它们也可以简单的分散在溶液中，可能形成大小或形状不均匀的聚集体。脂质是脂肪物质，可以是天然存在的或是合成的脂质。例如，脂质包括天然存在于细胞质中的脂肪滴，以及含有长链脂肪烃及其衍生物的一类化合物，例如脂肪酸、醇、胺、氨基醇和醛。
无论采用何种方法将外源核酸导入宿主细胞中或以其他方式将细胞暴露于本申请的抑制剂中，为了确认重组DNA序列存在于宿主细胞中，可以进行多种实验。这类实验包括例如本领域技术人员熟知的“分子生物学”实验。例如Southern和Northern blotting，RT-PCR和PCR；“生物化学”实验，例如检测某一特定多肽存在或不存在，例如通过免疫学方法(ELISAs和Western blots)或者通过本文所述的实验来进行鉴定均落入本申请范围内。
抗LIGHT抗体的制备
在一些实施例中，所述抗LIGHT抗体是单克隆抗体或源于单克隆抗体。在一些实施例中，所述抗LIGHT抗体包含来自单克隆抗体的VH和VL，或者其变体。在一些实施例中，所述抗LIGHT抗体进一步包括来自单克隆抗体的CH1和CL区域，或者其变体。单克隆抗体可以应用例如本领域已知的方法制备，包括杂交瘤细胞法、噬菌体展示方法或应用重组DNA法。此外，示例性的噬菌体展示法在本文及以下的实施例中进行了描述。
在杂交瘤细胞法中，通常采用免疫剂免疫仓鼠、小鼠或其他适合的宿主动物，以引发产生或能够产生与免疫剂特异性结合的抗体的淋巴细胞。或者，可以在体外免疫淋巴细胞。免疫剂可包括目标蛋白的多肽或融合蛋白。通常，如果需要人源细胞，采用外周血淋巴细胞(PBLs)，而如果需要非人哺乳动物来源细胞，则会使用脾细胞或淋巴结细胞。使用适当的融合剂将淋巴细胞与永生细胞系进行融合，例如聚乙二醇，以形成杂交瘤细胞。永生细胞系通常是转化的哺乳动物细胞，尤其是啮齿类、牛科和人源的骨髓瘤细胞。通常采用大鼠或小鼠骨髓瘤细胞系。杂交瘤细胞可以在合适的培养基中进行培养，所述培养基优选含有一种或多种抑制未融合永生细胞生长或存活的物质。例如，如果亲本细胞缺乏次黄嘌呤-鸟嘌呤磷酸核糖转移酶(HGPRT或HPRT)，则杂交瘤细胞培养基通常包括次黄嘌呤、氨蝶呤和胸苷(HAT培养基)，该培养基能阻止HGPRT缺陷细胞生长。
在一些实施例中，永生化细胞系有效融合，通过所选择的抗体生产细胞保证抗体高水平稳定表达，并且对某些培养基敏感，例如HAT培养基。在一些实施例中，永生细胞系是小鼠骨髓瘤细胞系，可以从例如，加利福尼亚圣地亚哥的索尔克细胞保藏中心和弗吉尼亚马纳萨斯的美国典型培养物保藏中心获得。同时还描述了人骨髓瘤和鼠-人杂交骨髓瘤细胞系用于制备人源单克隆抗体。
然后可以测定培养杂交瘤细胞的培养基中是否存在针对多肽的单克隆抗体。由杂交瘤细胞产生的单克隆抗体的结合特异性可以通过免疫沉淀法或体外结合实验确定，如放射性免疫测定法(RIA)或酶联免疫吸附法(ELISA)。此类技术或分析方法在本领域是已知的。单克隆抗体的结合亲和力可以通过例如Munson and Pollard,Anal.Biochem.,107:220(1980)中所述的斯卡查德(Scatchard)分析确定。
在鉴定出所需的杂交瘤细胞后，可以通过有限稀释法对目标克隆进行亚克隆，并通过标准方法进行培养。基于此目的适合的培养基包括，例如改良Eagle培养基(DMEM)和RPMI-1640培养基。或者，杂交瘤细胞可以在哺乳动物体内以腹水的形式生长。
亚克隆分泌的单克隆抗体可以通过常规免疫球蛋白纯化方法从培养基或腹水中分离或纯化，例如蛋白A-琼脂糖凝胶、羟基磷灰石色谱层析、凝胶电泳、透析或亲和层析。
在一些实施例中，根据本文所述的任一抗LIGHT抗体，所述抗LIGHT抗体包含选自抗体文库(例如展示scFv或Fab片段的噬菌体文库)的克隆的序列。所述克隆可以通过筛选具有所需活性的抗体片段组合文库的方法进行鉴定。例如，本领域已知多种方法用于产生噬菌体展示文库以及筛选这些文库来获得所需结合特性的抗体。这些方法在例如Hoogenboom et al.,Methods in Molecular Biology 178:1-37(O'Brien et al.,ed.,Human Press,Totowa,N.J.,2001)中进行了综述，并且在例如McCafferty et al.,Nature 348:552-554；Clackson et al.,Nature 352:624-628(1991)；Marks et al.,J.Mol.Biol.222:581-597(1992)；Marks and Bradbury,Methods in Molecular Biology 248:161-175(Lo,ed.,Human Press,Totowa,N.J.,2003)；Sidhu et al.,J.Mol.Biol.338(2):299-310(2004)；Lee et al.,J.Mol.Biol.340(5):1073-1093(2004)；Fellouse,Proc.Natl.Acad.Sci.USA 101(34):12467-12472(2004)；and Lee et al.,J.Immunol.Methods 284(1-2):119-132(2004)中进行了进一步描述。
在某些噬菌体展示方法中，通过聚合酶链式反应(PCR)分别克隆VH和VL基因的所有组成成分，并在噬菌体文库中随机重组，然后筛选能够结合抗原的噬菌体，如Winter et al.,Ann.Rev.Immunol.,12:433-455(1994)中所述。噬菌体通常以scFv片段或以Fab片段形式展示抗体片段。免疫来源的文库噬菌体提供针对免疫原的高亲和力抗体而不需要构建杂交瘤细胞。或者，可以克隆天然库(例如来自人)，来提供针对多种非自身抗原和自身抗原的单一抗体来源，而不需任何免疫，如Griffiths et al.,EMBO J,12:725-734(1993)中所述。最后，天然文库也可以通过克隆来自干细胞的非重排V-gene片段，并使用包含随机序列的PCR引物编码CDR3高变区并且在体外完成重排的方法进行制备，如Hoogenboom and Winter,J.Mol.Biol.,227:381-388(1992)中所述。描 述人抗体噬菌体文库的专利出版物包括，例如U.S.Pat.No.5,750,373和US Patent Publication Nos.2005/0079574、2005/0119455、2005/0266000、2007/0117126、2007/0160598、2007/0237764、2007/0292936和2009/0002360。
通过噬菌体展示筛选文库中能够特异性结合靶标LIGHT的抗LIGHT抗体部分的方法来制备所述的抗LIGHT抗体。该文库可以是人scFv噬菌体展示文库，具有至少1×109(例如至少1×109、2.5×109、5×109、7.5×109、1×1010、2.5×1010、5×1010、7.5×1010或1×1011)种多样性的独特的人抗体片段。在一些实施例中，所述文库是人天然文库，通过从健康受试者的PMBCs和脾脏中提取的DNA构建，包含所有人重链和轻链亚家族。在一些实施例中，所述文库是人天然文库，通过从各种疾病患者体内分离的PMBCs中提取的DNA构建，例如自身免疫病的患者、癌症患者和感染性疾病的患者。在一些实施例中，所述文库是半合成的人文库，其中重链CDR3完全是随机的，所有氨基酸(除了半胱氨酸)以相同的概率存在于任何给定的位置。(参见例如,Hoet,R.M.et al.,Nat.Biotechnol.23(3):344-348,2005)。在一些实施例中，半合成的人文库的重链CDR3长度在5到24个(例如5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、20、21、22、23或24个)氨基酸之间。在一些实施例中，所述文库是全合成的噬菌体展示文库。在一些实施例中，所述文库是非人噬菌体展示文库。
与靶标LIGHT具有高亲和力的噬菌体克隆可以通过噬菌体与靶标LIGHT的迭代结合进行筛选，所述靶标LIGHT与固相支持物结合(例如用于溶液淘选的珠子或用于细胞淘选的哺乳动物细胞)，接下来去除未结合的噬菌体，并洗脱特异性结合噬菌体。随后，洗脱结合的噬菌体克隆并用于感染合适的宿主细胞，例如E.coli XL1-Blue，进行表达和纯化。可以通过多轮淘选(例如，2、3、4、5、6或更多轮)，例如溶液淘选、细胞淘选或两者结合以富集特异性结合LIGHT的噬菌体克隆。富集的噬菌体克隆与靶标LIGHT的特异性结合可以通过本领域已知的任何方法进行检测，包括例如ELISA和FACS。
筛选抗体文库的另一种方法是在酵母细胞表面展示蛋白质。Wittrup等(美国专利6,699,658和6,696,251)开发了一种酵母细胞展示文库的方法。在此酵母展示系统中，一个组分包括锚定在酵母细胞壁上的酵母凝集素蛋白(Aga1)，另一个组分包括凝集素蛋白Aga2的第二个亚基，该亚基可以通过二硫键与Aga1蛋白结合进而展示在酵母细胞表面上。通过将Aga1基因整合到酵母染色体中来表达Aga1蛋白。将单链可变片段(scFv)文库与酵母展示质粒中的Aga2基因融合，将其转化后，该文库由于附加的营养标记的存在可保留在酵母中。Aga1和Aga2蛋白均在半乳糖诱导型启动子的控制下表达。
人抗体V基因库(VH和VK片段)是使用一组简并引物通过PCR方法获得(Sblattero，D.and Bradbury,A.Immunotechnology 3,271-278 1998)。PCR模板来自可商购的RNA或cDNA，包括PBMC，脾脏，淋巴结，骨髓和扁桃体。将独立的VH和VK PCR文库合并后，通过重叠延伸PCR将其组装成scFv形式(Sheets，M.D.et al,Proc.Natl.Acad.Sci.USA 95,6157–6162 1998)。为了构建酵母scFv展示文库，通过同源重组将所得的scFv PCR产物克隆到酵母中的酵母展示质粒中。 (Chao,G,et al,Nat Protoc.2006；1(2):755-68.Miller KD,et al.Current Protocols in Cytometry 4.7.1-4.7.30,2008)。
可以利用哺乳动物细胞展示系统来筛选抗LIGHT抗体，其中抗体部分展示在细胞表面上并通过抗原导向的筛选方法分离出特异性靶向LIGHT的抗体(如U.S.patent No.7,732,195B2中所述)。可以建立展示大量人类IgG抗体基因的中国仓鼠卵巢(CHO)细胞文库，并将其用于发现表达高亲和力抗体基因的克隆。已开发出另一种展示系统，该系统通过可变剪接使同一蛋白同时在细胞表面展示和分泌，其中展示的蛋白表型保持与基因型相关，使得可同时在生物物理和基于细胞功能的分析中表征该分泌的可溶性抗体。该方法克服了先前哺乳动物细胞展示的许多局限性，能够直接筛选和成熟化全长的、糖基化的IgGs形式的抗体(Peter M.Bowers,et al,Methods 2014,65：44-56)。瞬时表达系统适用于在抗体基因恢复之前进行的单轮抗原选择，因此对于从较小文库中选择抗体最有用。稳定的外显体载体提供了一种有吸引力的选择。外显体载体可以高效转染并稳定地维持在低拷贝数，从而允许多轮淘选以及更复杂抗体库的解析。
IgG文库是基于分离自一群人类供体的种系序列V基因片段与重排的(D)J区域的连接构建而成。将从2000个人体血液样本中收集的RNA反转录为cDNA，使用VH和VK特异性引物扩增VH和VK片段，并通过凝胶提取纯化。将VH和VK片段分别亚克隆到包含IgG1或K恒定区的展示载体中，然后电穿孔或转导293T到细胞，从而制备IgG文库。为了制备scFv抗体展示文库，连接VH和VK以产生scFv，然后亚克隆到展示载体中，再将其电穿孔或转导293T细胞。众所周知，IgG文库是基于分离自一群供体的种系序列V基因片段与重排的(D)J区域构建而成，供体可以是小鼠，大鼠，兔或猴。
单克隆抗体也可以通过重组DNA方法进行制备，例如U.S.Patent No.4,816,567中所述。编码本申请中所述单克隆抗体的DNA可以通过常规方法(例如通过能特异性结合编码鼠源抗体轻链和重链基因的寡聚核苷酸探针)轻易的分离和测序。如上所述的杂交瘤细胞或本申请的LIGHT特异性噬菌体克隆可以作为这种DNA的来源。分离后，可将DNA置于表达载体中，然后该载体转染入宿主细胞，例如猿猴COS细胞、中华仓鼠卵巢癌(CHO)细胞或不产生免疫球蛋白的骨髓瘤细胞中，获得在重组宿主细胞中合成的单克隆抗体。所述DNA也可以被修饰，例如用编码序列取代人重链和轻链恒定区和/或用框架区替换同源非人序列(U.S.Patent No.4,816,567；Morrison et al.,supra)，或通过共价键连接免疫球蛋白的编码序列的全部或部分非免疫球蛋白多肽的编码序列。这种非免疫球蛋白多肽可以取代本申请中抗体的恒定区，或可以取代本申请中抗体可变结构域中的一个抗原结合位点，形成嵌合的二价抗体。
所述抗体可以是单价抗体。制备单价抗体的方法是本领域已知的。例如，一种涉及免疫球蛋白轻链和修饰重链的重组表达方法。通常在Fc区的任意位置截短重链，以阻止重链相互交联。或者，相关的半胱氨酸残基被其它氨基酸残基取代或被缺失以防止交联。
体外方法也适用于制备单价抗体。消化抗体产生抗体片段，特别是Fab片段，可以使用任何本领域已知的方法完成。
具有所需结合特异性(抗体-抗原结合位点)的抗体可变结构域可以与免疫球蛋白恒定区融合。优选与免疫球蛋白重链恒定区进行融合，其包括至少部分铰链，CH2和CH3区。在一些实施例中，包含轻链结合必要位点的第一重链恒定区(CH1)至少出现在一种融合体中。编码免疫球蛋白重链融合体的DNA，如果需要，还可以包括编码免疫球蛋白轻链的DNA，被插入进独立的表达载体中，并共转染至合适的宿主生物中。
全人和人源化抗体
所述抗LIGHT抗体(如全长的抗LIGHT抗体)可以是全人抗体或人源化抗体。非人(如小鼠)抗体部分的人源化形式是嵌合的免疫球蛋白、免疫球蛋白链或其片段(例如Fv、Fab、Fab’、F(ab’)2、scFv或抗体的其他抗原结合子序列)，其通常包括最少的源于非人免疫球蛋白的序列。人源化抗体包括人免疫球蛋白、免疫球蛋白链或其片段(受体抗体)，其中受体CDR的残基被具有所需特异性、亲和力和性能的非人源(供体抗体)CDR残基取代，例如小鼠、大鼠或兔子的CDR。在一些实施例中，人免疫球蛋白Fv框架区残基被相应的非人源残基取代。人源化抗体还可以包含既不属于受体抗体也不在引入的CDR或框架区序列中的氨基酸残基。通常，人源化抗体包含至少一个，通常两个可变结构域，其中全部或基本上全部CDR区对应于非人免疫球蛋白的CDR区，全部或基本上全部框架区是人免疫球蛋白共有序列。
通常，人源化抗体含有一个或多个从非人源引入的氨基酸残基。那些非人源氨基酸残基通常被称为“移入”残基，通常来自“移入”可变结构域。根据一些实施例，人源化基本上可以按照Winter和其同事的如下方法进行(Jones et al.,Nature,321:522-525(1986)；Riechmann et al.,Nature,332:323-327(1988)；Verhoeyen et al.,Science,239:1534-1536(1988))，通过用啮齿动物CDRs或CDR序列取代人源抗体的相应序列。因此，这种“人源化”抗体部分(U.S.Patent No.4,816,567)，其基本上少于完整的人源抗体，其可变结构域已被来自非人源的相应序列所取代。在实际中，人源化抗体部分是典型的人源抗体部分，其中一些CDR残基和可能的一些框架区残基被来自啮齿类抗体中类似位点的残基所取代。
全人抗体是人源化的一种替代方式。例如，目前可以制备在免疫后能够产生完整的全人抗体文库而不产生内源性免疫球蛋白的转基因动物(例如，小鼠)。例如，已有报道，嵌合和种系突变小鼠中抗体重链连接区(JH)基因的纯合子缺失，完全抑制了内源性抗体的产生。将人种系免疫球蛋白基因阵列转移到这种种系突变小鼠体内，可在抗原刺激下产生人源抗体，参见，例如akobovits et al.,PNAS USA,90:2551(1993)；Jakobovits et al.,Nature,362:255-258(1993)；Bruggemann et al.,Year in Immunol.,7:33(1993)；U.S.Patent Nos.5,545,806,5,569,825,5,591,669,5,545,807；和WO 97/17852。或者，可以通过将人类免疫球蛋白基因座引入转基因动物中(例如内源性免疫球蛋白基因已经被部分或全部沉默的小鼠)来制备全人抗体。抗原刺激后，可以发现全人抗体的产生在各个方面都与其在人类中的产生非常相似，包括基因重排、组装和抗体文库。这种方法在例如U.S.Patent Nos.5,545,807；5,545,806；5,569,825；5,625,126；5,633,425；and 5,661,016,and Marks et al.,Bio/Technology,10:779-783(1992)；Lonberg et al.,Nature,368:856-859(1994)； Morrison,Nature,368:812-813(1994)；Fishwild et al.,Nature Biotechnology,14:845-851(1996)；Neuberger,Nature Biotechnology,14:826(1996)；Lonberg and Huszar,Intern.Rev.Immunol.,13:65-93(1995)中进行了描述。
全人抗体也以通过体外活化B细胞(见U.S.Patents 5,567,610and 5,229,275)或通过使用本领域已知的各种技术来产生，包括噬菌体展示文库。Hoogenboom and Winter,J.Mol.Biol.,227:381(1991)；Marks et al.,J.Mol.Biol.,222:581(1991).Cole et al.和Boerner et al.等人的技术也可以用于制备全人单克隆抗体。见Cole et al.,Monoclonal Antibodies and Cancer Therapy,Alan R.Liss,p.77(1985)and Boerner et al.,J.Immunol.,147(1):86-95(1991)。
抗LIGHT抗体变体
在一些实施例中，本文提供的抗LIGHT抗体变体(例如，全长的抗LIGHT抗体)的氨基酸序列也在考虑中。例如，可能需要改善抗体的结合亲和力和/或其它生物学活性。抗体变体的氨基酸序列可以通过在编码抗体的核苷酸序列中引入适当的修饰或通过肽合成来制备。此类修饰包括例如，抗体氨基酸序列中残基的缺失和/或插入和/或取代。可以通过氨基酸残基缺失、插入和取代的任一组合来完成最终的构建，使其具有所需的特征。例如，抗原结合性。
在一些实施例中，提供具有一个或多个氨基酸取代的抗LIGHT抗体变体。取代突变的目标位点包括高变区(HVRs)和框架区(FRs)。可以在目标抗体中引入氨基酸取代，筛选所需活性的产物，例如，改善的生物活性，保持/改善抗原结合能力，降低的免疫原性，或改善的ADCC或CDC。
保守取代如下表4所示。
表4保守取代

根据侧链性质将氨基酸分为不同类别：
a、疏水氨基酸：去甲亮氨酸Norleucine、蛋氨酸Met、丙氨酸Ala、缬氨酸Val、亮氨酸
Leu、异亮氨酸Ile；
b、中性亲水性氨基酸：半胱氨酸Cys、丝氨酸Ser、苏氨酸Thr、天冬酰胺Asn、谷氨酰胺Gln；
c、酸性氨基酸：天冬氨酸Asp、谷氨酸Glu；
d、碱性氨基酸：组氨酸His、赖氨酸Lys、精氨酸Arg；
e、含有影响链方向的氨基酸：甘氨酸Gly、脯氨酸Pro；
f、芳香族氨基酸：色氨酸Trp、酪氨酸Tyr、苯丙氨酸Phe。
非保守氨基酸的取代包含将以上一种类别取代为另一种类别。
一种示例性的取代变体是亲和力成熟的抗体，可采用例如以噬菌体展示为基础的亲和力成熟技术而方便地产生。简言之，将一个或多个CDR残基进行突变，变体抗体部分展示在噬菌体上，并筛选具有特定生物活性(例如，基于CD3激动剂和LIGHT共刺激原代T细胞活化增殖的抑制实验或结合亲和力的生物学活性)的变体。可以在HVRs区进行改变(例如，取代)来获得改善的基于CD3激动剂和LIGHT共刺激原代T细胞增殖的抑制实验或结合亲和力的生物学活性。可以在HVR的“热点区”产生改变，即在体细胞成熟过程中发生高频突变的密码子编码的残基(参见，例如Chowdhury,Methods Mol.Biol.207:179-196(2008))，和/或在特异的决定性残基(SDRs)，检测所得变体VH和VL的结合亲和力。从二级文库中构建和重新选择亲和力成熟的方法已经在一些文献中进行描述，例如，Hoogenboom et al.in Methods in Molecular Biology 178:1-37(O'Brien et al.,ed.,Human Press,Totowa,NJ,(2001))。
在一些亲和力成熟的实施例中，通过多种方法中的任一种(例如易错PCR，链改组或寡核苷酸定向突变)，将多样性引入选择的用于亲和力成熟的可变基因中。然后创建二级文库。对该文库进行筛选，鉴定出具有所需亲和力的抗体变体。另一种引入多样性的方法包括HVR介导的方式，其中几个HVR残基(例如，一次4-6个残基)被随机化。涉及抗原结合的HVR残基被特异性地识别，例如，采用丙氨酸扫描诱变或建模。通常CDR-H3和CDR-L3区域尤其是重点靶标。
在一些实施例中，取代、插入或缺失可能发生在一个或多个HVRs内，只要这种改变基本上不降低抗体结合抗原的能力。例如，可以在HVRs中产生基本上不降低结合亲和力的保守性改变(例如，本文中提供的保守性取代)。这些改变可能发生在HVR“热点区”或SDRs区域之外。在一些实施例中上文提供的变体VH和VL序列，每一个HVR或者是未发生改变，或者包含不超过1个、2个或3个氨基酸取代。
一种有用的可以鉴定出抗体中能被靶向性突变的氨基酸残基或区域的方法称为“丙氨酸扫描突变”，如Cunningham and Wells(1989)Science,244:1081-1085中所述。在该方法中，一个或一组目标残基(例如，带电残基如精氨酸、天冬氨酸、组氨酸、赖氨酸和谷氨酸)被中性或带负电荷 氨基酸(例如，丙氨酸或谷氨酸)取代，以此来确定抗体与抗原相互作用是否受到影响。可以在氨基酸的位置进一步引入取代，来证明该位置对初始取代具有功能敏感性。或者/另外，通过抗原-抗体复合物的晶体结构来鉴定抗体和抗原之间的接触位点。这些接触位点残基和邻近残基可作为取代候选物而被靶向或消除。筛选变体，确定它们是否具有所需要的性质。
氨基酸序列的插入，包括在氨基端和/或羧基末端的融合，长度范围从1个残基到包含100个或更多个残基的多肽，还包括在序列内插入1个或多个氨基酸残基。末端插入的例子包括N末端具有甲硫氨酰残基的抗体。抗体分子的其它插入变体，包括在抗体分子N-末端或C-末端融合一个酶(例如，ADEPT)或增加抗体血清半衰期的多肽。
Fc区变体
在一些实施例中，将一个或多个氨基酸修饰引入本文所述的抗体(例如，全长抗LIGHT抗体或抗LIGHT抗体融合蛋白)的Fc区，从而产生Fc区变体。在一些实施例中，Fc区变体具有增强的ADCC效能，通常与结合Fc的受体(FcRs)有关。在一些实施例中，Fc区变体具有降低的ADCC效能。有很多关于Fc序列的改变或突变影响其效能的例子，例如，WO 00/42072和Shields et al.J Biol.Chem.9(2):6591-6604(2001)描述了与FcRs的结合增强或减弱的抗体变体。这些出版物的内容通过引用并入本文。
抗体依赖的细胞介导的细胞毒作用(ADCC)是治疗性抗体针对肿瘤细胞的作用机制。ADCC是细胞介导的免疫防御，当靶细胞膜表面的抗原被特异性抗体(例如，抗LIGHT抗体)结合，免疫系统的效应细胞主动裂解靶细胞(例如，癌细胞)。通常ADCC效应涉及由抗体激活的NK细胞。NK细胞表达Fc受体CD16。该受体识别并结合与靶细胞表面相结合的抗体分子的Fc部分。NK细胞表面最常见的Fc受体为CD16或FcγRIII。Fc受体与抗体Fc区的结合导致NK细胞的活化，释放细胞裂解颗粒，随后靶细胞凋亡。ADCC对肿瘤细胞的杀伤作用可以通过转染高亲和力FcR的NK-92细胞的特异性实验来测定。其结果与不表达FcR的野生型NK-92进行比较。
在一些实施例中，本申请还提供抗LIGHT抗体变体(例如全长抗LIGHT抗体变体)，其包含具有部分但不是全部的效应功能Fc区，使得其在体内具有延长的半衰期，然而特定的效应功能(例如CDC或ADCC)是非必需的或有害的，这种抗LIGHT抗体成为本申请理想的候选。通过在体外和/或体内进行细胞毒性检测来确认CDC和/或ADCC活性的减少/消除。例如，通过Fc受体(FcR)结合试验来确认抗体缺乏FcγR结合能力(因此可能缺乏ADCC活性)但依然保留FcRn的结合能力。介导ADCC的主要细胞中，NK细胞仅表达FcγRIII，而单核细胞表达FcγRI、FcγRII和FcγRIII。Ravetch and Kinet Annu.Rev.Immunol.9:457-492(1991)第464页的表3中总结了FcR在造血细胞上的表达。在体外评估目标分子的ADCC活性的非限制性实例在U.S.Pat.No.5,500,362中进行了描述(参见例如Hellstrom,I.et al.Proc.Nat'l Acad.Sci.USA 83:7059-7063(1986)and Hellstrom,I et al.,Proc.Nat'l Acad.Sci.USA 82:1499-1502(1985)；U.S.Pat.No.5,821,337(see Bruggemann,M.et al.,J.Exp.Med.166:1351-1361(1987))。或者，可以采用非放射性检测方法(参见，例如ACTITM流式细胞术非放射性细胞毒性检测(CellTechnology,Inc.Mountain View, Calif.)和CYTOTOX 96TM非放射性细胞毒性检测(Promega,Madison,Wis.))。此类检测实验采用的效应细胞包括外周血单核细胞(PBMC)和自然杀伤细胞(NK)。或者，另外地，目标分子的ADCC活性在体内进行检测，例如，在动物模型中，如Clynes et al.Proc.Nat'l Acad.Sci.USA 95:652-656(1998)中所述。同时还可以进行C1q结合试验来确认抗体不能与C1q结合，从而缺乏CDC活性。参见，例如WO 2006/029879和WO 2005/100402中C1q和C3c结合ELISA。为了评估补体激活情况，可进行CDC检测(参见，例如Gazzano-Santoro et al.,J.Immunol.Methods 202:163(1996)；Cragg,M.S.et al.,Blood 101:1045-1052(2003)；和Cragg,M.S.and M.J.Glennie,Blood 103:2738-2743(2004))。使用本领域已知的方法来测定FcRn结合和体内清除/半衰期(参见，例如，Petkova,S.B.et al.,Int'l.Immunol.18(12):1759-1769(2006))。
具有降低的效应功能的抗体，包括在Fc区残基238、265、269、270、297、327和329位进行一个或多个残基的取代(U.S.Pat.No.6,737,056)。这些Fc变体包括在265、269、270、297和327位进行两个或多个残基的取代的Fc变体，包括被称为“DANA”的Fc变体，其在265和297位残基取代为丙氨酸(U.S.Pat.No.7,332,581)。
这类与FcRs结合能力提高或降低的抗体变体已有描述(参见例如U.S.Pat.No.6,737,056；WO2004/056312，和Shields et al.,J.Biol.Chem.9(2):6591-6604(2001))。
在一些实施例中，提供一种抗LIGHT抗体(例如全长的抗LIGHT抗体)变体，其包含具有一个或多个能够增强ADCC效应的氨基酸取代的Fc区变体。在一些实施例中，Fc区变体包含一个或多个能够增强ADCC效应的氨基取代，这些取代的位置在Fc区的298、333和/或334位(EU残基编号)。在一些实施例中，所述抗LIGHT抗体(例如，全长的抗LIGHT抗体)变体包括在Fc区的S298A，E333A和K334A位氨基酸取代。
在一些实施例中，Fc区的改变导致C1q结合和/或补体依赖性细胞毒作用(CDC)的改变(即增强或减弱)，参见U.S.Pat.No.6,194,551,WO 99/51642，和Idusogie et al.,J.Immunol.164:4178-4184(2000)中所述。
在一些实施例中，提供一种抗LIGHT抗体(例如全长的抗LIGHT抗体)变体，其包含具有一个或多个氨基酸取代的Fc区变体，能够延长半衰期或增强与Fc受体(FcRn)的结合。具有延长半衰期和改善FcRn结合的抗体在US 2005/0014934A1(Hinton等)中有所描述。这些抗体Fc区包含一个或多个氨基酸取代，增强了Fc区与FcRn的结合。这些Fc变体在Fc区包含238、256、265、272、286、303、305、307、311、312、317、340、356、360、362、376、378、380、382、413、424或434位的残基中的一个或多个取代，例如Fc区434位残基的取代(U.S.Pat.No.7,371,826)。
同时参见Duncan&Winter,Nature 322:738-40(1988)；U.S.Pat.No.5,648,260；U.S.Pat.No.5,624,821和WO 94/29351中提供其它Fc区变体的例子。
本申请考虑了包括本文所述的任一种Fc变体或其组合的抗LIGHT抗体(例如全长抗LIGHT抗体)。
糖基化变体
在一些实施例中，对本文所提供的抗LIGHT抗体(例如全长抗LIGHT抗体)进行改变，以增加或降低抗NGF抗体糖基化的程度。通过改变抗NGF抗体或其多肽部分的氨基酸序列以此来增加或去除一个或多个糖基化位点，可以方便地实现添加或删除抗LIGHT抗体上的糖基化位点。
其中抗LIGHT抗体包含Fc区，可以改变与其连接的糖。由哺乳动物细胞产生的天然抗体通常包含分支的双触角寡糖，该寡糖通常通过N-连接与Fc区CH2结构域Asn297连接，参见例如Wright et al.，TIBTECH 15:26-32(1997)。所述寡糖可包含多种糖类，例如甘露糖、N-乙酰氨基葡萄糖苷(GlcNAc)、半乳糖和唾液酸，以及与双触角寡糖结构“茎”部的GlcNAc相连接的海藻糖。在一些实施例中，可对本申请的抗LIGHT抗体进行寡糖修饰，从而产生具有某些改进特性的抗LIGHT抗体变体。
与Fc区的CH2结构域连接的N-聚糖是异质的。CHO细胞中产生的抗体或Fc融合蛋白通过岩藻糖基转移酶活性被岩藻糖基化，参见Shoji-Hosaka et al.,J.Biochem.2006,140:777-83。通常，可以在人血清中检测出一小部分天然存在的非岩藻糖基化IgGs。Fc区的N-糖基化对于其与FcγR结合很重要；而非岩藻糖基化的N-聚糖增强了Fc与FcγRIIIa的结合能力。与FcRIIIa结合能力增强使得ADCC效应增强，这在需要细胞毒性的某些抗体治疗应用中是有利的。
在一些实施例中，当不需要Fc介导的细胞毒作用时，增强的效应功能可能是有害的。在一些实施例中，Fc片段或CH2结构域是非糖基化的。在一些实施例中，通过对CH2结构域中的N-糖基化位点进行突变以阻止其糖基化。
在一些实施例中，提供抗LIGHT抗体(例如全长的抗LIGHT抗体)变体，其包含Fc区，其中连接于Fc区的糖类结构具有减少的岩藻糖或缺乏岩藻糖，这可能会增强ADCC功能。具体地，本文提供抗LIGHT抗体，其相对于野生型CHO细胞产生的相同抗LIGHT抗体具有减少的岩藻糖。也就是说，它们的特征在于，与天然CHO细胞(例如，产生天然糖基化形式的CHO细胞，含有天然FUT8基因的CHO细胞)产生的抗体相比，具有更少量的岩藻糖。在一些实施例中，所述抗LIGHT抗体的N-连接聚糖具有少于50％、40％、30％、20％、10％或5％的岩藻糖。例如，该抗LIGHT抗体的岩藻糖含量可能是1％-80％、1％-65％、5％-65％或20％-40％。在一些实施例中，所述抗LIGHT抗体的N-连接聚糖不包含岩藻糖，即，其中抗LIGHT抗体完全不含岩藻糖，或没有岩藻糖或是去岩藻糖基化。岩藻糖的含量是通过计算连接到Asn297上的糖链内岩藻糖平均含量相对于通过MALDI-TOF质谱测量的所有连接在Asn297上的糖结构(如复合、杂交或甘露糖结构)的总量来确定的，如WO 2008/077546所述。Asn297是指位于Fc区297位的天冬酰胺残基(EU Fc区残基编号体系)。然而，由于抗体的微小序列变化，Asn297也可位于297位的上游或下游±3个氨基酸，即在294和300位之间。这些岩藻糖基化变体可能具有增强的ADCC功能。参见例如US Patent Publication Nos.US 2003/0157108(Presta,L.)，US 2004/0093621(Kyowa Hakko Kogyo Co.,Ltd)。与“去岩藻糖基化”或“岩藻糖缺乏”的抗体变体相关的出版物的实例包括，US 2003/0157108；WO 2000/61739；WO 2001/29246；US 2003/0115614；US 2002/0164328；US  2004/0093621；US 2004/0132140；US 2004/0110704；US 2004/0110282；US 2004/0109865；WO 2003/085119；WO 2003/084570；WO 2005/035586；WO 2005/035778；WO 2005/053742；WO 2002/031140；Okazaki et al.J.Mol.Biol.336:1239-1249(2004)；Yamane-Ohnuki et al.Biotech.Bioeng.87:614(2004)。能够产生去岩藻糖基化抗体的细胞系包括缺乏蛋白岩藻糖基化功能的Lec13CHO细胞(Ripka et al.Arch.Biochem.Biophys.249:533-545(1986)；US Pat Appl No US 2003/0157108 A1,Presta,L；和WO 2004/056312 A1,Adams et al.,尤其是实施例11)，和基因敲除细胞系，例如α-1,6-岩藻糖基转移酶基因，FUT8基因敲除的CHO细胞(参见Yamane-Ohnuki et al.Biotech.Bioeng.87:614(2004)；Kanda,Y.et al.,Biotechnol.Bioeng.,94(4):680-688(2006)；和WO2003/085107)。
抗LIGHT抗体(例如全长抗LIGHT抗体)变体进一步提供二等分寡糖，例如，其中连接于抗LIGHT抗体Fc区的双触角寡糖被GlcNAc等分。这种抗LIGHT抗体(例如全长的抗LIGHT抗体)变体可能具有减少的岩藻糖基化和/或增强的ADCC功能。这类抗体变体的实例在WO 2003/011878(Jean-Mairet et al.)；U.S.Pat.No.6,602,684(Umana et al.)；US 2005/0123546(Umana et al.)，和Ferrara et al.,Biotechnology and Bioengineering,93(5):851-861(2006)中有所描述。还提供抗LIGHT抗体(例如全长的抗LIGHT抗体)变体，其在与Fc区连接的寡糖中具有至少一个半乳糖残基。这类抗LIGHT抗体变体可能具有增强的CDC功能。这类变体在例如WO1997/30087(Patel et al.)；WO 1998/58964(Raju,S.)；和WO 1999/22764(Raju,S.)中有所描述。
在一些实施例中，所述抗LIGHT抗体(例如全长抗LIGHT抗体)变体包含能与FcγRIII结合的Fc区。在一些实施例中，包含Fc区的所述抗LIGHT抗体(例如全长抗LIGHT抗体)变体在人效应细胞(例如T细胞)存在下具有ADCC活性，或者与具有人野生型IgG1Fc区的其他相同抗LIGHT抗体(例如全长抗LIGHT抗体)相比，在人效应细胞存在下，具有增强的ADCC活性。
半胱氨酸工程变体
在一些实施例中，需要制备半胱氨酸工程化的抗LIGHT抗体(例如全长抗LIGHT抗体)，在该抗体中一个或多个氨基酸残基被半胱氨酸残基取代。在一些实施例中，取代残基出现在抗LIGHT抗体的可及位点。通过用半胱氨酸取代那些残基，具有活性的巯基基团位于抗LIGHT抗体的可及位点，可以用于将该抗LIGHT抗体与其它部分偶联，例如药物部分或接头-药物部分，来制备如本文中进一步描述的抗LIGHT免疫偶联物。半胱氨酸工程化的抗LIGHT抗体(例如，全长抗LIGHT抗体)可以按照例如U.S.Pat.No.7,521,541所述进行制备。
衍生物
在一些实施例中，本文所提供的抗LIGHT抗体(例如全长抗LIGHT抗体)可进一步修饰以包含本领域已知并且容易获得的其它非蛋白部分。适用于衍生化抗LIGHT抗体的部分包括，但不限于，水溶性聚合物。水溶性聚合物的非限制性实例包括，但不限于，聚乙二醇(PEG)、乙二醇/丙二醇共聚物、羧甲基纤维素、右旋糖酐、聚乙烯醇、聚乙烯吡咯烷酮、聚-1,3-二氧戊烷、聚- 1,3,6-三氧杂环已烷、乙烯/马来酸酐共聚物、聚氨基酸(均聚物或无规共聚物)、右旋糖酐或聚(n-乙烯基吡咯烷酮)聚乙二醇、丙二醇均聚物、环氧丙烷/环氧乙烷共聚物、聚氧乙基化多元醇(例如甘油)、聚乙烯醇及其混合物。聚乙二醇丙醛由于其在水中的稳定性，在制造中具有优势。聚合物可以具有任意分子量，可以是支链或非支链的。连接在抗LIGHT抗体上的聚合物数量可以变化，并且如果连接多于一个多聚物，它们可以是相同的或不同的分子。通常，用于衍生化的聚合物的数量和/或类型可基于以下考虑因素来确定，包括但不限于，需要改进抗LIGHT抗体的特性或功能，抗LIGHT抗体衍生物是否用于特定条件下的治疗等。
药物组合物
本文还提供包含任一种抗LIGHT抗体(例如全长抗LIGHT抗体)、编码抗体的核酸、包含编码抗体的核酸的载体或者包含本文所述的核酸或载体的宿主细胞的组合物(例如药物组合物，在这里也称为制剂)。在一些实施例中，提供一种药物组合物，包含本文所述的任一种抗LIGHT抗体和药学上可接受的载体。
可通过混合具有所需纯度的抗LIGHT抗体与任选的药学上可接受的载体、赋形剂或稳定剂(Remington's Pharmaceutical Sciences 16th edition,Osol,A.Ed.(1980))获得合适的抗LIGHT抗体制剂，制备成冻干制剂或液体制剂形式。可接受的载体、赋形剂或稳定剂在所用剂量和浓度下对接受者无毒，包括缓冲剂如：磷酸盐、柠檬酸和其它有机酸；抗氧化剂，包括抗坏血酸和蛋氨酸；防腐剂(例如十八烷基二甲基苄基氯化铵；六甲基氯化铵；苯扎氯铵；苄索氯铵；苯酚；丁醇或苄醇；对羟基苯甲酸烷基酯，如对羟基苯甲酸甲酯或对羟基苯甲酸丙酯；邻苯二酚；间苯二酚；环己醇；3-戊醇和间甲酚)；低分子量(少于10个残基)多肽；蛋白质，例如血清白蛋白、明胶或免疫球蛋白；亲水性聚合物，如聚乙烯吡咯烷酮；氨基酸，例如甘氨酸、谷氨酰胺、天冬酰胺、组氨酸、精氨酸或赖氨酸；单糖、二糖和其它碳水化合物，包括葡萄糖、甘露糖或糊精；螯合剂如EDTA；糖类，如蔗糖、甘露醇、海藻糖或山梨糖醇；成盐反离子如钠；金属复合物(如锌-蛋白复合物)；和/或非离子表面活性剂如TWEENTM，PLURONICSTM或聚乙二醇(PEG)；示例性制剂如WO98/56418中所述，并通过引用明确并入本文。适合皮下给药的冻干制剂在WO97/04801中有所描述。这类冻干制剂可通过合适的稀释剂重构成高蛋白浓度的制剂，并且重构的制剂可以通过皮下给药的方式给予本文中待治疗个体。阳离子脂质体或脂质体可以用于将本申请中的抗LIGHT抗体递送至细胞。
本文所述的制剂除包含抗LIGHT抗体(例如全长抗LIGHT抗体)之外，还可以包含一种或多种治疗特定病症所必要的其它活性物质，优选具有活性互补且彼此无不良反应的物质。例如，除了抗LIGHT抗体之外，可能需要进一步包含类固醇，非类固醇消炎药(NSAIDS)(例如水杨酸类、丙酸衍生物、乙酸衍生物、烯醇酸衍生物、邻氨基苯基酸衍生物、选择性COX-2抑制剂和磺酰苯胺)，糖皮质激素(如皮质醇、可的松、强的松、泼尼松龙、地塞米松、倍他米松、曲安西龙等)，细胞抑制剂(如烷化剂、抗代谢物、甲氨蝶呤、硫唑嘌呤、巯基嘌呤或细胞毒性抗生 素)，TNF抑制剂，IL-12抑制剂，IL-23抑制剂，α4β7整合素抑制剂。这些分子以对预期目的有效的量组合存在。其它物质的有效量取决于制剂中的抗LIGHT抗体的含量，疾病或病症或治疗的类型，以及如上所述的其它因素。这些药物通常以与本文描述的相同剂量和给药途径使用，或者以目前应用剂量的1％至99％使用。
所述抗LIGHT抗体(例如，全长抗LIGHT抗体)也可以包埋在例如通过凝聚技术和界面聚合制备的微胶囊中，例如分别在胶体药物递送系统(例如，脂质体、白蛋白微球、微乳液、纳米颗粒和纳米胶囊)中或粗乳液中的羟甲基纤维素或明胶-微胶囊和聚(甲基丙烯酸甲酯)微胶囊。可以制备缓释制剂。
可以制备抗LIGHT抗体(例如，全长抗LIGHT抗体)的缓释制剂。缓释制剂的适合的实例包括含有抗体(或其片段)的固体疏水聚合物半透性基质，这些基质是成型制品的形式，例如，薄膜或微胶囊。缓释基质的实例包括聚酯、水凝胶(例如，聚(2-羟乙基甲基丙烯酸酯)或聚(乙烯醇))、聚乳酸(U.S.Pat.No.3,773,919)，L-谷氨酸和L-谷氨酸乙酯共聚物，不可降解的乙烯-醋酸乙烯酯，可降解的乳酸-乙醇酸共聚物如LUPRON DEPOTTM(由乳酸-乙醇酸共聚物和醋酸亮丙瑞林组成的可注射微球)以及聚-D(-)-3-羟基丁酸。虽然诸如乙烯-醋酸乙烯酯和乳酸-乙醇酸之类的聚合物可以使分子的释放超过100天，某些水凝胶可以在更短的时间内释放蛋白质。当包封的抗体在体内长时间停留时，它们会因暴露于37℃的潮湿环境中发生变性或聚集，可能导致生物活性的丧失或免疫原性的改变。可以根据相应的机制，设计合理的策略来稳定抗LIGHT抗体。例如，如果发现聚集机制是通过硫代二硫化物交换形成分子间S-S键，则可以通过修饰巯基残基、在酸性溶液中冻干、控制含水量、使用适当的添加剂、以及开发特定的聚合物基质组合物来实现稳定化。
在一些实施例中，所述抗LIGHT抗体(例如全长抗LIGHT抗体)配制在含有柠檬酸盐、氯化钠、乙酸盐、琥珀酸盐、甘氨酸、聚山梨酯80(吐温80)或上述任何组合的缓冲液中。
用于体内给药的制剂必须是无菌的。这可以通过例如应用无菌过滤膜过滤而容易地实现。
使用抗LIGHT抗体的治疗方法
抗LIGHT抗体(例如，全长的抗LIGHT抗体)和/或本申请所述的组合物可以施用于个体(例如，哺乳动物，如人类)来治疗与LIGHT信号通路失调导致的疾病和/或病症(例如，自身免疫性疾病和/或炎症性疾病)，这些疾病包括但不限于炎性肠道疾病(IBD)、克罗恩疾病、溃疡性结肠炎、强直性脊柱炎、异位性皮炎、类风湿性关节炎、细支气管炎、移植排斥反应、同种移植排斥反应、移植物抗宿主病(GVHD)、哮喘、嗜酸性食管炎、急性呼吸窘迫综合征(ARDS)、慢性心脏衰竭、慢性阻塞性肺病(COPD)、败血性休克、纤维化疾病、皮肤纤维化、特发性肺纤维化、肾纤维化、慢性肾病、系统性硬化、多发性硬化症、斯耶格伦氏综合征、狼疮、气道炎症、银屑病、肝炎、乳糜泻、原发性胆汁肝硬化、自身免疫性溶血性贫血、自身免疫性新生儿血小板减少症、原发性血小板减少性紫癜、非酒精性脂肪肝、COVID19。因此，本申请在一些实施例中，提 供一种治疗LIGHT信号通路失调导致的疾病和/或病症(例如，自身免疫性疾病和/或炎症性疾病)的方法，包括向个体施用有效量的包含抗LIGHT抗体(例如，全长的抗LIGHT抗体)的组合物(例如，药物组合物)，例如本文所述的任一种抗LIGHT抗体(例如，全长的抗LIGHT抗体)，在一些实施例中，所述个体是人类。
例如，在一些实施例中，提供一种用于治疗患有与LIGHT信号通路相关的疾病(例如，自身免疫性疾病和/或炎症性疾病)的个体的方法，包括向所述个体施用有效量的包含特异性结合人LIGHT上表位的LIGHT抗体(例如，全长抗LIGHT抗体)的药物组合物，其中所述表位包含人LIGHT的位氨基酸残基。在一些实施例中，所述抗LIGHT抗体是全长抗体。在一些实施例中，所述全长抗LIGHT抗体是IgG1或IgG4抗体。在一些实施例中，所述疾病或病症选自例如，炎性肠道疾病(IBD)、克罗恩疾病、溃疡性结肠炎、强直性脊柱炎、异位性皮炎、类风湿性关节炎、细支气管炎、移植排斥反应、同种移植排斥反应、移植物抗宿主病(GVHD)、哮喘、嗜酸性食管炎、急性呼吸窘迫综合征(ARDS)、慢性心脏衰竭、慢性阻塞性肺病(COPD)、败血性休克、纤维化疾病、皮肤纤维化、特发性肺纤维化、肾纤维化、慢性肾病、系统性硬化、多发性硬化症、斯耶格伦氏综合征、狼疮、气道炎症、银屑病、肝炎、乳糜泻、原发性胆汁肝硬化、自身免疫性溶血性贫血、自身免疫性新生儿血小板减少症、原发性血小板减少性紫癜、非酒精性脂肪肝、COVID19。在一些实施例中，所述个体是人类。
例如，在一些实施例中，提供一种用于治疗患有与LIGHT信号通路相关的疾病(例如，自身免疫性疾病和/或炎症性疾病)的个体的方法，包括向所述个体施用有效量的包含抗LIGHT抗体(例如，全长抗LIGHT抗体)的药物组合物，其中所述抗体包含：重链可变结构域(VH)，所述VH包含：重链互补决定区(HC-CDR)1，其包含GYFIN(SEQ ID NO:1)；HC-CDR2，其包含RIYPYNVX1TFYNQNFKG(SEQ ID NO:45)，其中X1为D或N；和HC-CDR3，其包含GTHYYGSSGAMDY(SEQ ID NO:16)；以及轻链可变结构域(VL)，所述VL包含：轻链互补决定区(LC-CDR)1，其包含KASQNVGTAVA(SEQ ID NO:23)；LC-CDR2，其包含SASNRYT(SEQ ID NO:30)；和LC-CDR3，其包含QQYSSYPYT(SEQ ID NO:37)。在一些实施例中，所述抗LIGHT抗体是全长抗体。在一些实施例中，所述全长抗LIGHT抗体是IgG1或IgG4抗体。在一些实施例中，所述疾病或病症选自例如，炎性肠道疾病(IBD)、克罗恩疾病、溃疡性结肠炎、强直性脊柱炎、异位性皮炎、类风湿性关节炎、细支气管炎、移植排斥反应、同种移植排斥反应、移植物抗宿主病(GVHD)、哮喘、嗜酸性食管炎、急性呼吸窘迫综合征(ARDS)、慢性心脏衰竭、慢性阻塞性肺病(COPD)、败血性休克、纤维化疾病、皮肤纤维化、特发性肺纤维化、肾纤维化、慢性肾病、系统性硬化、多发性硬化症、斯耶格伦氏综合征、狼疮、气道炎症、银屑病、肝炎、乳糜泻、原发性胆汁肝硬化、自身免疫性溶血性贫血、自身免疫性新生儿血小板减少症、原发性血小板减少性紫癜、非酒精性脂肪肝、COVID19。在一些实施例中，所述个体是人类。
在一些实施例中，提供一种用于治疗患有与LIGHT信号通路相关的疾病(例如，自身免疫性疾病和/或炎症性疾病)的个体的方法，包括向所述个体施用有效量的包含抗LIGHT抗体的组合物，其中所述抗体包含VH，所述VH包含：HC-CDR1，其包含SEQ ID NO:1所示的氨基酸序列，HC-CDR2，其包含SEQ ID NOs:8-9中任一所示的氨基酸序列，和HC-CDR3，其包含SEQ ID NO:16所示的氨基酸序列，或者所述VH的变体，其HC-CDRs中包含至多约5个氨基酸的取代；以及VL，所述VL包含：LC-CDR1，其包含SEQ ID NO:23所示的氨基酸序列，LC-CDR2，其包含SEQ ID NO:30所示的氨基酸序列，和LC-CDR3，其包含SEQ ID NO:37所示的氨基酸序列，或者所述VL的变体，其LC-CDRs中包含至多约5个氨基酸的取代。
在一些实施例中，提供一种用于治疗患有与LIGHT信号通路相关的疾病(例如，自身免疫性疾病和/或炎症性疾病)的个体的方法，包括向所述个体施用有效量的包含抗LIGHT抗体的组合物，其中所述抗体包含：VH，所述VH包含SEQ ID NOs:46-53中任一所示的氨基酸序列或其变体，所述变体与SEQ ID NOs:46-53中任一所示的氨基酸序列具有至少约80％序列同一性；以及VL，所述VL包含SEQ ID NOs:62-65中任一所示的氨基酸序列或其变体，所述变体与SEQ ID NOs:62-65中任一所示的氨基酸序列具有至少约80％序列同一性。
在一些实施例中，本文所述抗LIGHT抗体是包含IgG1或IgG4恒定区的全长抗LIGHT抗体。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种用于治疗患有与LIGHT信号通路相关的疾病(例如，自身免疫性疾病和/或炎症性疾病)的个体的方法，包括向所述个体施用有效量的包含抗LIGHT抗体的组合物，其中所述抗体包含：VH，所述VH包含：HC-CDR1，其包含氨基酸序列SEQ ID NO:1，HC-CDR2，其包含氨基酸序列SEQ ID NO:8，和HC-CDR3，其包含氨基酸序列SEQ ID NO:16，或者所述VH的变体，其HC-CDRs中包含至多约5个氨基酸的取代；以及VL，所述VL包含：LC-CDR1，其包含氨基酸序列SEQ ID NO:23，LC-CDR2，其包含氨基酸序列SEQ ID NO:30，和LC-CDR3，其包含氨基酸序列SEQ ID NO:37，或者所述VL的变体，其LC-CDRs中包含至多约5个氨基酸的取代。
在一些实施例中，本文所述抗LIGHT抗体包含：VH，所述VH包含氨基酸序列SEQ ID NO:46或其变体，所述变体与氨基酸序列SEQ ID NO:46具有至少约80％序列同一性；以及VL，所述VL包含氨基酸序列SEQ ID NO:62或其变体，所述变体与氨基酸序列SEQ ID NO:62具有至少约80％序列同一性。在一些实施例中，本文所述抗LIGHT抗体是包含IgG1或IgG4恒定区的全长抗LIGHT抗体。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，重链恒定 区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，本文所述抗LIGHT抗体包含：VH，所述VH包含氨基酸序列SEQ ID NO:47或其变体，所述变体与氨基酸序列SEQ ID NO:47具有至少约80％序列同一性；以及VL，所述VL包含氨基酸序列SEQ ID NO:63或其变体，所述变体与氨基酸序列SEQ ID NO:63具有至少约80％序列同一性。在一些实施例中，本文所述抗LIGHT抗体是包含IgG1或IgG4恒定区的全长抗LIGHT抗体。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，本文所述抗LIGHT抗体包含：VH，所述VH包含氨基酸序列SEQ ID NO:48或其变体，所述变体与氨基酸序列SEQ ID NO:48具有至少约80％序列同一性；以及VL，所述VL包含氨基酸序列SEQ ID NO:63或其变体，所述变体与氨基酸序列SEQ ID NO:63具有至少约80％序列同一性。在一些实施例中，本文所述抗LIGHT抗体是包含IgG1或IgG4恒定区的全长抗LIGHT抗体。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，本文所述抗LIGHT抗体包含：VH，所述VH包含氨基酸序列SEQ ID NO:49或其变体，所述变体与氨基酸序列SEQ ID NO:49具有至少约80％序列同一性；以及VL，所述VL包含氨基酸序列SEQ ID NO:63或其变体，所述变体与氨基酸序列SEQ ID NO:63具有至少约80％序列同一性。在一些实施例中，本文所述抗LIGHT抗体是包含IgG1或IgG4恒定区的全长抗LIGHT抗体。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，本文所述抗LIGHT抗体包含：VH，所述VH包含氨基酸序列SEQ ID NO:50或其变体，所述变体与氨基酸序列SEQ ID NO:50具有至少约80％序列同一性；以及VL，所述VL包含氨基酸序列SEQ ID NO:63或其变体，所述变体与氨基酸序列SEQ ID NO:63具有至少约80％序列同一性。在一些实施例中，本文所述抗LIGHT抗体是包含IgG1或IgG4恒定区的全长抗LIGHT抗体。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，本文所述抗LIGHT抗体包含：VH，所述VH包含氨基酸序列SEQ ID NO:47或其变体，所述变体与氨基酸序列SEQ ID NO:47具有至少约80％序列同一性；以及VL，所述VL包含氨基酸序列SEQ ID NO:64或其变体，所述变体与氨基酸序列SEQ ID NO:64具有至少约80％序列同一性。在一些实施例中，本文所述抗LIGHT抗体是包含IgG1或IgG4恒定区的全长抗LIGHT抗体。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，本文所述抗LIGHT抗体包含：VH，所述VH包含氨基酸序列SEQ ID NO:48或其变体，所述变体与氨基酸序列SEQ ID NO:48具有至少约80％序列同一性；以及VL，所述VL包含氨基酸序列SEQ ID NO:64或其变体，所述变体与氨基酸序列SEQ ID NO:64具有至少约80％序列同一性。在一些实施例中，本文所述抗LIGHT抗体是包含IgG1或IgG4恒定区的全长抗LIGHT抗体。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，本文所述抗LIGHT抗体包含：VH，所述VH包含氨基酸序列SEQ ID NO:49或其变体，所述变体与氨基酸序列SEQ ID NO:49具有至少约80％序列同一性；以及VL，所述VL包含氨基酸序列SEQ ID NO:64或其变体，所述变体与氨基酸序列SEQ ID NO:64具有至少约80％序列同一性。在一些实施例中，本文所述抗LIGHT抗体是包含IgG1或IgG4恒定区的全长抗LIGHT抗体。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，本文所述抗LIGHT抗体包含：VH，所述VH包含氨基酸序列SEQ ID NO:50或其变体，所述变体与氨基酸序列SEQ ID NO:50具有至少约80％序列同一性；以及VL，所述VL包含氨基酸序列SEQ ID NO:64或其变体，所述变体与氨基酸序列SEQ ID NO:64具有至少约80％序列同一性。在一些实施例中，本文所述抗LIGHT抗体是包含IgG1或IgG4恒定区的全长抗LIGHT抗体。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，本文所述抗LIGHT抗体包含：VH，所述VH包含氨基酸序列SEQ ID NO:47或其变体，所述变体与氨基酸序列SEQ ID NO:47具有至少约80％序列同一性；以及VL，所述VL 包含氨基酸序列SEQ ID NO:65或其变体，所述变体与氨基酸序列SEQ ID NO:65具有至少约80％序列同一性。在一些实施例中，本文所述抗LIGHT抗体是包含IgG1或IgG4恒定区的全长抗LIGHT抗体。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，本文所述抗LIGHT抗体包含：VH，所述VH包含氨基酸序列SEQ ID NO:48或其变体，所述变体与氨基酸序列SEQ ID NO:48具有至少约80％序列同一性；以及VL，所述VL包含氨基酸序列SEQ ID NO:65或其变体，所述变体与氨基酸序列SEQ ID NO:65具有至少约80％序列同一性。在一些实施例中，本文所述抗LIGHT抗体是包含IgG1或IgG4恒定区的全长抗LIGHT抗体。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，本文所述抗LIGHT抗体包含：VH，所述VH包含氨基酸序列SEQ ID NO:49或其变体，所述变体与氨基酸序列SEQ ID NO:49具有至少约80％序列同一性；以及VL，所述VL包含氨基酸序列SEQ ID NO:65或其变体，所述变体与氨基酸序列SEQ ID NO:65具有至少约80％序列同一性。在一些实施例中，本文所述抗LIGHT抗体是包含IgG1或IgG4恒定区的全长抗LIGHT抗体。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，本文所述抗LIGHT抗体包含：VH，所述VH包含氨基酸序列SEQ ID NO:50或其变体，所述变体与氨基酸序列SEQ ID NO:50具有至少约80％序列同一性；以及VL，所述VL包含氨基酸序列SEQ ID NO:65或其变体，所述变体与氨基酸序列SEQ ID NO:65具有至少约80％序列同一性。在一些实施例中，本文所述抗LIGHT抗体是包含IgG1或IgG4恒定区的全长抗LIGHT抗体。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种用于治疗患有与LIGHT信号通路相关的疾病(例如，自身免疫性疾病和/或炎症性疾病)的个体的方法，包括向所述个体施用有效量的包含抗LIGHT抗体的组合物，其中所述抗体包含：VH，所述VH包含：HC-CDR1，其包含氨基酸序列SEQ ID NO:1，HC-CDR2，其包含氨基酸序列SEQ ID NO:9，和HC-CDR3，其包含氨基酸序列SEQ ID NO:16，或者 所述VH的变体，其HC-CDRs中包含至多约5个氨基酸的取代；以及VL，所述VL包含：LC-CDR1，其包含氨基酸序列SEQ ID NO:23，LC-CDR2，其包含氨基酸序列SEQ ID NO:30，和LC-CDR3，其包含氨基酸序列SEQ ID NO:37，或者所述VL的变体，其LC-CDRs中包含至多约5个氨基酸的取代。
在一些实施例中，本文所述抗LIGHT抗体包含：VH，所述VH包含氨基酸序列SEQ ID NO:51或其变体，所述变体与氨基酸序列SEQ ID NO:51具有至少约80％序列同一性；以及VL，所述VL包含氨基酸序列SEQ ID NO:63或其变体，所述变体与氨基酸序列SEQ ID NO:63具有至少约80％序列同一性。在一些实施例中，本文所述抗LIGHT抗体是包含IgG1或IgG4恒定区的全长抗LIGHT抗体。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，本文所述抗LIGHT抗体包含：VH，所述VH包含氨基酸序列SEQ ID NO:52或其变体，所述变体与氨基酸序列SEQ ID NO:52具有至少约80％序列同一性；以及VL，所述VL包含氨基酸序列SEQ ID NO:65或其变体，所述变体与氨基酸序列SEQ ID NO:65具有至少约80％序列同一性。在一些实施例中，本文所述抗LIGHT抗体是包含IgG1或IgG4恒定区的全长抗LIGHT抗体。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，本文所述抗LIGHT抗体包含：VH，所述VH包含氨基酸序列SEQ ID NO:53或其变体，所述变体与氨基酸序列SEQ ID NO:53具有至少约80％序列同一性；以及VL，所述VL包含氨基酸序列SEQ ID NO:65或其变体，所述变体与氨基酸序列SEQ ID NO:65具有至少约80％序列同一性。在一些实施例中，本文所述抗LIGHT抗体是包含IgG1或IgG4恒定区的全长抗LIGHT抗体。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，本文所述抗LIGHT抗体包含：VH，所述VH包含氨基酸序列SEQ ID NO:51或其变体，所述变体与氨基酸序列SEQ ID NO:51具有至少约80％序列同一性；以及VL，所述VL包含氨基酸序列SEQ ID NO:65或其变体，所述变体与氨基酸序列SEQ ID NO:65具有至少约80％序列同一性。在一些实施例中，本文所述抗LIGHT抗体是包含IgG1或IgG4恒定区的全长抗LIGHT抗体。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，重链恒定 区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
例如，在一些实施例中，提供一种用于治疗患有与LIGHT信号通路相关的疾病(例如，自身免疫性疾病和/或炎症性疾病)的个体的方法，包括向所述个体施用有效量的包含抗LIGHT抗体(例如，全长抗LIGHT抗体)的药物组合物，其中所述抗体包含：重链可变结构域(VH)，所述VH包含：HC-CDR1，其包含氨基酸序列SEQ ID NO:2，HC-CDR2，其包含氨基酸序列SEQ ID NO:10，和HC-CDR3，其包含氨基酸序列SEQ ID NO:17，或者所述VH的变体，其HC-CDRs中包含至多约5个氨基酸的取代；以及轻链可变结构域(VL)，所述VL包含：LC-CDR1，其包含氨基酸序列SEQ ID NO:24，LC-CDR2，其包含氨基酸序列SEQ ID NO:31，和LC-CDR3，其包含氨基酸序列SEQ ID NO:38，或者所述VL的变体，其LC-CDRs中包含至多约5个氨基酸的取代。在一些实施例中，所述抗LIGHT抗体是全长抗体。在一些实施例中，所述全长抗LIGHT抗体是IgG1或IgG4抗体。在一些实施例中，所述疾病或病症选自例如，炎性肠道疾病(IBD)、克罗恩疾病、溃疡性结肠炎、强直性脊柱炎、异位性皮炎、类风湿性关节炎、细支气管炎、移植排斥反应、同种移植排斥反应、移植物抗宿主病(GVHD)、哮喘、嗜酸性食管炎、急性呼吸窘迫综合征(ARDS)、慢性心脏衰竭、慢性阻塞性肺病(COPD)、败血性休克、纤维化疾病、皮肤纤维化、特发性肺纤维化、肾纤维化、慢性肾病、系统性硬化、多发性硬化症、斯耶格伦氏综合征、狼疮、气道炎症、银屑病、肝炎、乳糜泻、原发性胆汁肝硬化、自身免疫性溶血性贫血、自身免疫性新生儿血小板减少症、原发性血小板减少性紫癜、非酒精性脂肪肝、COVID19。在一些实施例中，所述个体是人类。
在一些实施例中，提供一种用于治疗患有与LIGHT信号通路相关的疾病(例如，自身免疫性疾病和/或炎症性疾病)的个体的方法，包括向所述个体施用有效量的包含抗LIGHT抗体的组合物，其中所述抗体包含：VH，所述VH包含SEQ ID NO:54所示的氨基酸序列或其变体，所述变体与SEQ ID NO:54所示的氨基酸序列具有至少约80％序列同一性；以及VL，所述VL包含SEQ ID NO:66所示的氨基酸序列或其变体，所述变体与SEQ ID NO:66所示的氨基酸序列具有至少约80％序列同一性。
在一些实施例中，本文所述抗LIGHT抗体是包含IgG1或IgG4恒定区的全长抗LIGHT抗体。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
例如，在一些实施例中，提供一种用于治疗患有与LIGHT信号通路相关的疾病(例如，自身免疫性疾病和/或炎症性疾病)的个体的方法，包括向所述个体施用有效量的包含抗LIGHT抗体(例如，全长抗LIGHT抗体)的药物组合物，其中所述抗体包含：重链可变结构域(VH)，所述VH包含：HC-CDR1，其包含氨基酸序列SEQ ID NO:2，HC-CDR2，其包含氨基酸序列SEQ ID  NO:10，和HC-CDR3，其包含氨基酸序列SEQ ID NO:17，或者所述VH的变体，其HC-CDRs中包含至多约5个氨基酸的取代；以及轻链可变结构域(VL)，所述VL包含：LC-CDR1，其包含氨基酸序列SEQ ID NO:25，LC-CDR2，其包含氨基酸序列SEQ ID NO:31，和LC-CDR3，其包含氨基酸序列SEQ ID NO:39，或者所述VL的变体，其LC-CDRs中包含至多约5个氨基酸的取代。在一些实施例中，所述抗LIGHT抗体是全长抗体。在一些实施例中，所述全长抗LIGHT抗体是IgG1或IgG4抗体。在一些实施例中，所述疾病或病症选自例如，炎性肠道疾病(IBD)、克罗恩疾病、溃疡性结肠炎、强直性脊柱炎、异位性皮炎、类风湿性关节炎、细支气管炎、移植排斥反应、同种移植排斥反应、移植物抗宿主病(GVHD)、哮喘、嗜酸性食管炎、急性呼吸窘迫综合征(ARDS)、慢性心脏衰竭、慢性阻塞性肺病(COPD)、败血性休克、纤维化疾病、皮肤纤维化、特发性肺纤维化、肾纤维化、慢性肾病、系统性硬化、多发性硬化症、斯耶格伦氏综合征、狼疮、气道炎症、银屑病、肝炎、乳糜泻、原发性胆汁肝硬化、自身免疫性溶血性贫血、自身免疫性新生儿血小板减少症、原发性血小板减少性紫癜、非酒精性脂肪肝、COVID19。在一些实施例中，所述个体是人类。
在一些实施例中，提供一种用于治疗患有与LIGHT信号通路相关的疾病(例如，自身免疫性疾病和/或炎症性疾病)的个体的方法，包括向所述个体施用有效量的包含抗LIGHT抗体的组合物，其中所述抗体包含：VH，所述VH包含SEQ ID NO:55所示的氨基酸序列或其变体，所述变体与SEQ ID NO:55所示的氨基酸序列具有至少约80％序列同一性；以及VL，所述VL包含SEQ ID NO:67所示的氨基酸序列或其变体，所述变体与SEQ ID NO:67所示的氨基酸序列具有至少约80％序列同一性。
在一些实施例中，本文所述抗LIGHT抗体是包含IgG1或IgG4恒定区的全长抗LIGHT抗体。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
例如，在一些实施例中，提供一种用于治疗患有与LIGHT信号通路相关的疾病(例如，自身免疫性疾病和/或炎症性疾病)的个体的方法，包括向所述个体施用有效量的包含抗LIGHT抗体(例如，全长抗LIGHT抗体)的药物组合物，其中所述抗体包含：重链可变结构域(VH)，所述VH包含：HC-CDR1，其包含氨基酸序列SEQ ID NO:3，HC-CDR2，其包含氨基酸序列SEQ ID NO:11，和HC-CDR3，其包含氨基酸序列SEQ ID NO:18，或者所述VH的变体，其HC-CDRs中包含至多约5个氨基酸的取代；以及轻链可变结构域(VL)，所述VL包含：LC-CDR1，其包含氨基酸序列SEQ ID NO:26，LC-CDR2，其包含氨基酸序列SEQ ID NO:32，和LC-CDR3，其包含氨基酸序列SEQ ID NO:40，或者所述VL的变体，其LC-CDRs中包含至多约5个氨基酸的取代。在一些实施例中，所述抗LIGHT抗体是全长抗体。在一些实施例中，所述全长抗LIGHT抗体是IgG1或IgG4抗体。在一些实施例中，所述疾病或病症选自例如，炎性肠道疾病(IBD)、克罗恩疾 病、溃疡性结肠炎、强直性脊柱炎、异位性皮炎、类风湿性关节炎、细支气管炎、移植排斥反应、同种移植排斥反应、移植物抗宿主病(GVHD)、哮喘、嗜酸性食管炎、急性呼吸窘迫综合征(ARDS)、慢性心脏衰竭、慢性阻塞性肺病(COPD)、败血性休克、纤维化疾病、皮肤纤维化、特发性肺纤维化、肾纤维化、慢性肾病、系统性硬化、多发性硬化症、斯耶格伦氏综合征、狼疮、气道炎症、银屑病、肝炎、乳糜泻、原发性胆汁肝硬化、自身免疫性溶血性贫血、自身免疫性新生儿血小板减少症、原发性血小板减少性紫癜、非酒精性脂肪肝、COVID19。在一些实施例中，所述个体是人类。
在一些实施例中，提供一种用于治疗患有与LIGHT信号通路相关的疾病(例如，自身免疫性疾病和/或炎症性疾病)的个体的方法，包括向所述个体施用有效量的包含抗LIGHT抗体的组合物，其中所述抗体包含：VH，所述VH包含SEQ ID NO:56所示的氨基酸序列或其变体，所述变体与SEQ ID NO:56所示的氨基酸序列具有至少约80％序列同一性；以及VL，所述VL包含SEQ ID NO:68所示的氨基酸序列或其变体，所述变体与SEQ ID NO:68所示的氨基酸序列具有至少约80％序列同一性。
在一些实施例中，本文所述抗LIGHT抗体是包含IgG1或IgG4恒定区的全长抗LIGHT抗体。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
例如，在一些实施例中，提供一种用于治疗患有与LIGHT信号通路相关的疾病(例如，自身免疫性疾病和/或炎症性疾病)的个体的方法，包括向所述个体施用有效量的包含抗LIGHT抗体(例如，全长抗LIGHT抗体)的药物组合物，其中所述抗体包含：重链可变结构域(VH)，所述VH包含：HC-CDR1，其包含氨基酸序列SEQ ID NO:3，HC-CDR2，其包含氨基酸序列SEQ ID NO:11，和HC-CDR3，其包含氨基酸序列SEQ ID NO:18，或者所述VH的变体，其HC-CDRs中包含至多约5个氨基酸的取代；以及轻链可变结构域(VL)，所述VL包含：LC-CDR1，其包含氨基酸序列SEQ ID NO:26，LC-CDR2，其包含氨基酸序列SEQ ID NO:32，和LC-CDR3，其包含氨基酸序列SEQ ID NO:41，或者所述VL的变体，其LC-CDRs中包含至多约5个氨基酸的取代。在一些实施例中，所述抗LIGHT抗体是全长抗体。在一些实施例中，所述全长抗LIGHT抗体是IgG1或IgG4抗体。在一些实施例中，所述疾病或病症选自例如，炎性肠道疾病(IBD)、克罗恩疾病、溃疡性结肠炎、强直性脊柱炎、异位性皮炎、类风湿性关节炎、细支气管炎、移植排斥反应、同种移植排斥反应、移植物抗宿主病(GVHD)、哮喘、嗜酸性食管炎、急性呼吸窘迫综合征(ARDS)、慢性心脏衰竭、慢性阻塞性肺病(COPD)、败血性休克、纤维化疾病、皮肤纤维化、特发性肺纤维化、肾纤维化、慢性肾病、系统性硬化、多发性硬化症、斯耶格伦氏综合征、狼疮、气道炎症、银屑病、肝炎、乳糜泻、原发性胆汁肝硬化、自身免疫性溶血性贫血、自身免疫性新生 儿血小板减少症、原发性血小板减少性紫癜、非酒精性脂肪肝、COVID19。在一些实施例中，所述个体是人类。
在一些实施例中，提供一种用于治疗患有与LIGHT信号通路相关的疾病(例如，自身免疫性疾病和/或炎症性疾病)的个体的方法，包括向所述个体施用有效量的包含抗LIGHT抗体的组合物，其中所述抗体包含：VH，所述VH包含SEQ ID NO:57所示的氨基酸序列或其变体，所述变体与SEQ ID NO:57所示的氨基酸序列具有至少约80％序列同一性；以及VL，所述VL包含SEQ ID NO:69所示的氨基酸序列或其变体，所述变体与SEQ ID NO:69所示的氨基酸序列具有至少约80％序列同一性。
在一些实施例中，本文所述抗LIGHT抗体是包含IgG1或IgG4恒定区的全长抗LIGHT抗体。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
例如，在一些实施例中，提供一种用于治疗患有与LIGHT信号通路相关的疾病(例如，自身免疫性疾病和/或炎症性疾病)的个体的方法，包括向所述个体施用有效量的包含抗LIGHT抗体(例如，全长抗LIGHT抗体)的药物组合物，其中所述抗体包含：重链可变结构域(VH)，所述VH包含：HC-CDR1，其包含氨基酸序列SEQ ID NO:4，HC-CDR2，其包含氨基酸序列SEQ ID NO:12，和HC-CDR3，其包含氨基酸序列SEQ ID NO:19，或者所述VH的变体，其HC-CDRs中包含至多约5个氨基酸的取代；以及轻链可变结构域(VL)，所述VL包含：LC-CDR1，其包含氨基酸序列SEQ ID NO:27，LC-CDR2，其包含氨基酸序列SEQ ID NO:33，和LC-CDR3，其包含氨基酸序列SEQ ID NO:42，或者所述VL的变体，其LC-CDRs中包含至多约5个氨基酸的取代。在一些实施例中，所述抗LIGHT抗体是全长抗体。在一些实施例中，所述全长抗LIGHT抗体是IgG1或IgG4抗体。在一些实施例中，所述疾病或病症选自例如，炎性肠道疾病(IBD)、克罗恩疾病、溃疡性结肠炎、强直性脊柱炎、异位性皮炎、类风湿性关节炎、细支气管炎、移植排斥反应、同种移植排斥反应、移植物抗宿主病(GVHD)、哮喘、嗜酸性食管炎、急性呼吸窘迫综合征(ARDS)、慢性心脏衰竭、慢性阻塞性肺病(COPD)、败血性休克、纤维化疾病、皮肤纤维化、特发性肺纤维化、肾纤维化、慢性肾病、系统性硬化、多发性硬化症、斯耶格伦氏综合征、狼疮、气道炎症、银屑病、肝炎、乳糜泻、原发性胆汁肝硬化、自身免疫性溶血性贫血、自身免疫性新生儿血小板减少症、原发性血小板减少性紫癜、非酒精性脂肪肝、COVID19。在一些实施例中，所述个体是人类。
在一些实施例中，提供一种用于治疗患有与LIGHT信号通路相关的疾病(例如，自身免疫性疾病和/或炎症性疾病)的个体的方法，包括向所述个体施用有效量的包含抗LIGHT抗体的组合物，其中所述抗体包含：VH，所述VH包含SEQ ID NO:58所示的氨基酸序列或其变体，所述变体与SEQ ID NO:58所示的氨基酸序列具有至少约80％序列同一性；以及VL，所述VL包含SEQ ID  NO:70所示的氨基酸序列或其变体，所述变体与SEQ ID NO:70所示的氨基酸序列具有至少约80％序列同一性。
在一些实施例中，本文所述抗LIGHT抗体是包含IgG1或IgG4恒定区的全长抗LIGHT抗体。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
例如，在一些实施例中，提供一种用于治疗患有与LIGHT信号通路相关的疾病(例如，自身免疫性疾病和/或炎症性疾病)的个体的方法，包括向所述个体施用有效量的包含抗LIGHT抗体(例如，全长抗LIGHT抗体)的药物组合物，其中所述抗体包含：重链可变结构域(VH)，所述VH包含：HC-CDR1，其包含氨基酸序列SEQ ID NO:5，HC-CDR2，其包含氨基酸序列SEQ ID NO:13，和HC-CDR3，其包含氨基酸序列SEQ ID NO:20，或者所述VH的变体，其HC-CDRs中包含至多约5个氨基酸的取代；以及轻链可变结构域(VL)，所述VL包含：LC-CDR1，其包含氨基酸序列SEQ ID NO:28，LC-CDR2，其包含氨基酸序列SEQ ID NO:34，和LC-CDR3，其包含氨基酸序列SEQ ID NO:43，或者所述VL的变体，其LC-CDRs中包含至多约5个氨基酸的取代。在一些实施例中，所述抗LIGHT抗体是全长抗体。在一些实施例中，所述全长抗LIGHT抗体是IgG1或IgG4抗体。在一些实施例中，所述疾病或病症选自例如，炎性肠道疾病(IBD)、克罗恩疾病、溃疡性结肠炎、强直性脊柱炎、异位性皮炎、类风湿性关节炎、细支气管炎、移植排斥反应、同种移植排斥反应、移植物抗宿主病(GVHD)、哮喘、嗜酸性食管炎、急性呼吸窘迫综合征(ARDS)、慢性心脏衰竭、慢性阻塞性肺病(COPD)、败血性休克、纤维化疾病、皮肤纤维化、特发性肺纤维化、肾纤维化、慢性肾病、系统性硬化、多发性硬化症、斯耶格伦氏综合征、狼疮、气道炎症、银屑病、肝炎、乳糜泻、原发性胆汁肝硬化、自身免疫性溶血性贫血、自身免疫性新生儿血小板减少症、原发性血小板减少性紫癜、非酒精性脂肪肝、COVID19。在一些实施例中，所述个体是人类。
在一些实施例中，提供一种用于治疗患有与LIGHT信号通路相关的疾病(例如，自身免疫性疾病和/或炎症性疾病)的个体的方法，包括向所述个体施用有效量的包含抗LIGHT抗体的组合物，其中所述抗体包含：VH，所述VH包含SEQ ID NO:59所示的氨基酸序列或其变体，所述变体与SEQ ID NO:59所示的氨基酸序列具有至少约80％序列同一性；以及VL，所述VL包含SEQ ID NO:71所示的氨基酸序列或其变体，所述变体与SEQ ID NO:71所示的氨基酸序列具有至少约80％序列同一性。
在一些实施例中，本文所述抗LIGHT抗体是包含IgG1或IgG4恒定区的全长抗LIGHT抗体。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，重链恒定区包含或由 氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
例如，在一些实施例中，提供一种用于治疗患有与LIGHT信号通路相关的疾病(例如，自身免疫性疾病和/或炎症性疾病)的个体的方法，包括向所述个体施用有效量的包含抗LIGHT抗体(例如，全长抗LIGHT抗体)的药物组合物，其中所述抗体包含：重链互补决定区(HC-CDR)1，其包含DHIMN(SEQ ID NO:6)；HC-CDR2，其包含RIYPVSGETNYNQKFMG(SEQ ID NO:14)；和HC-CDR3，其包含GSYYWNAMDY(SEQ ID NO:21)；以及轻链可变结构域(VL)，所述VL包含：轻链互补决定区(LC-CDR)1，其包含KASQSVDFDGDSYMN(SEQ ID NO:29)或KASQSVDFDGESYMN(SEQ ID NO:83)；LC-CDR2，其包含SASNLES(SEQ ID NO:35)；和LC-CDR3，其包含QQSIEDPWT(SEQ ID NO:43)。在一些实施例中，所述抗LIGHT抗体是全长抗体。在一些实施例中，所述全长抗LIGHT抗体是IgG1或IgG4抗体。在一些实施例中，所述疾病或病症选自例如，炎性肠道疾病(IBD)、克罗恩疾病、溃疡性结肠炎、强直性脊柱炎、异位性皮炎、类风湿性关节炎、细支气管炎、移植排斥反应、同种移植排斥反应、移植物抗宿主病(GVHD)、哮喘、嗜酸性食管炎、急性呼吸窘迫综合征(ARDS)、慢性心脏衰竭、慢性阻塞性肺病(COPD)、败血性休克、纤维化疾病、皮肤纤维化、特发性肺纤维化、肾纤维化、慢性肾病、系统性硬化、多发性硬化症、斯耶格伦氏综合征、狼疮、气道炎症、银屑病、肝炎、乳糜泻、原发性胆汁肝硬化、自身免疫性溶血性贫血、自身免疫性新生儿血小板减少症、原发性血小板减少性紫癜、非酒精性脂肪肝、COVID19。在一些实施例中，所述个体是人类。
在一些实施例中，提供一种用于治疗患有与LIGHT信号通路相关的疾病(例如，自身免疫性疾病和/或炎症性疾病)的个体的方法，包括向所述个体施用有效量的包含抗LIGHT抗体(例如，全长抗LIGHT抗体)的药物组合物，其中所述抗体包含：重链可变结构域(VH)，所述VH包含：HC-CDR1，其包含氨基酸序列SEQ ID NO:6，HC-CDR2，其包含氨基酸序列SEQ ID NO:14，和HC-CDR3，其包含氨基酸序列SEQ ID NO:21，或者所述VH的变体，其HC-CDRs中包含至多约5个氨基酸的取代；以及轻链可变结构域(VL)，所述VL包含：LC-CDR1，其包含SEQ ID NOs:29或83中任一所示的氨基酸序列，LC-CDR2，其包含氨基酸序列SEQ ID NO:35，和LC-CDR3，其包含氨基酸序列SEQ ID NO:43，或者所述VL的变体，其LC-CDRs中包含至多约5个氨基酸的取代。在一些实施例中，所述抗LIGHT抗体是全长抗体。在一些实施例中，所述全长抗LIGHT抗体是IgG1或IgG4抗体。在一些实施例中，所述疾病或病症选自例如，炎性肠道疾病(IBD)、克罗恩疾病、溃疡性结肠炎、强直性脊柱炎、异位性皮炎、类风湿性关节炎、细支气管炎、移植排斥反应、同种移植排斥反应、移植物抗宿主病(GVHD)、哮喘、嗜酸性食管炎、急性呼吸窘迫综合征(ARDS)、慢性心脏衰竭、慢性阻塞性肺病(COPD)、败血性休克、纤维化疾病、皮肤纤维化、特发性肺纤维化、肾纤维化、慢性肾病、系统性硬化、多发性硬化症、斯耶格伦氏综合征、狼疮、气道炎症、银屑病、肝炎、乳糜泻、原发性胆汁肝硬化、自身免疫性溶血性贫血、自 身免疫性新生儿血小板减少症、原发性血小板减少性紫癜、非酒精性脂肪肝、COVID19。在一些实施例中，所述个体是人类。
在一些实施例中，提供一种用于治疗患有与LIGHT信号通路相关的疾病(例如，自身免疫性疾病和/或炎症性疾病)的个体的方法，包括向所述个体施用有效量的包含抗LIGHT抗体的组合物，其中所述抗体包含：VH，所述VH包含SEQ ID NOs:60，84-85中任一所示的氨基酸序列或其变体，所述变体与SEQ ID NOs:60，84-85中任一所示的氨基酸序列具有至少约80％序列同一性；以及VL，所述VL包含SEQ ID NOs:72，86-91中任一所示的氨基酸序列或其变体，所述变体与SEQ ID NOs:72，86-91中任一所示的氨基酸序列具有至少约80％序列同一性。
在一些实施例中，本文所述抗LIGHT抗体是包含IgG1或IgG4恒定区的全长抗LIGHT抗体。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种用于治疗患有与LIGHT信号通路相关的疾病(例如，自身免疫性疾病和/或炎症性疾病)的个体的方法，包括向所述个体施用有效量的包含抗LIGHT抗体(例如，全长抗LIGHT抗体)的药物组合物，其中所述抗体包含：重链可变结构域(VH)，所述VH包含：HC-CDR1，其包含氨基酸序列SEQ ID NO:6，HC-CDR2，其包含氨基酸序列SEQ ID NO:14，和HC-CDR3，其包含氨基酸序列SEQ ID NO:21，或者所述VH的变体，其HC-CDRs中包含至多约5个氨基酸的取代；以及轻链可变结构域(VL)，所述VL包含：LC-CDR1，其包含氨基酸序列SEQ ID NO:29，LC-CDR2，其包含氨基酸序列SEQ ID NO:35，和LC-CDR3，其包含氨基酸序列SEQ ID NO:43，或者所述VL的变体，其LC-CDRs中包含至多约5个氨基酸的取代。在一些实施例中，所述抗LIGHT抗体是全长抗体。在一些实施例中，所述全长抗LIGHT抗体是IgG1或IgG4抗体。在一些实施例中，所述疾病或病症选自例如，炎性肠道疾病(IBD)、克罗恩疾病、溃疡性结肠炎、强直性脊柱炎、异位性皮炎、类风湿性关节炎、细支气管炎、移植排斥反应、同种移植排斥反应、移植物抗宿主病(GVHD)、哮喘、嗜酸性食管炎、急性呼吸窘迫综合征(ARDS)、慢性心脏衰竭、慢性阻塞性肺病(COPD)、败血性休克、纤维化疾病、皮肤纤维化、特发性肺纤维化、肾纤维化、慢性肾病、系统性硬化、多发性硬化症、斯耶格伦氏综合征、狼疮、气道炎症、银屑病、肝炎、乳糜泻、原发性胆汁肝硬化、自身免疫性溶血性贫血、自身免疫性新生儿血小板减少症、原发性血小板减少性紫癜、非酒精性脂肪肝、COVID19。在一些实施例中，所述个体是人类。
在一些实施例中，提供一种用于治疗患有与LIGHT信号通路相关的疾病(例如，自身免疫性疾病和/或炎症性疾病)的个体的方法，包括向所述个体施用有效量的包含抗LIGHT抗体的组合物，其中所述抗体包含：VH，所述VH包含SEQ ID NO:60所示的氨基酸序列或其变体，所述变体与SEQ ID NO:60所示的氨基酸序列具有至少约80％序列同一性；以及VL，所述VL包含SEQ ID  NO:72所示的氨基酸序列或其变体，所述变体与SEQ ID NO:72所示的氨基酸序列具有至少约80％序列同一性。在一些实施例中，本文所述抗LIGHT抗体是包含IgG1或IgG4恒定区的全长抗LIGHT抗体。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，本文所述抗LIGHT抗体包含：VH，所述VH包含氨基酸序列SEQ ID NO:84或其变体，所述变体与氨基酸序列SEQ ID NO:84具有至少约80％序列同一性；以及VL，所述VL包含氨基酸序列SEQ ID NO:86或其变体，所述变体与氨基酸序列SEQ ID NO:86具有至少约80％序列同一性。在一些实施例中，本文所述抗LIGHT抗体是包含IgG1或IgG4恒定区的全长抗LIGHT抗体。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，本文所述抗LIGHT抗体包含：VH，所述VH包含氨基酸序列SEQ ID NO:85或其变体，所述变体与氨基酸序列SEQ ID NO:85具有至少约80％序列同一性；以及VL，所述VL包含氨基酸序列SEQ ID NO:87或其变体，所述变体与氨基酸序列SEQ ID NO:87具有至少约80％序列同一性。在一些实施例中，本文所述抗LIGHT抗体是包含IgG1或IgG4恒定区的全长抗LIGHT抗体。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，本文所述抗LIGHT抗体包含：VH，所述VH包含氨基酸序列SEQ ID NO:84或其变体，所述变体与氨基酸序列SEQ ID NO:84具有至少约80％序列同一性；以及VL，所述VL包含氨基酸序列SEQ ID NO:88或其变体，所述变体与氨基酸序列SEQ ID NO:88具有至少约80％序列同一性。在一些实施例中，本文所述抗LIGHT抗体是包含IgG1或IgG4恒定区的全长抗LIGHT抗体。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种用于治疗患有与LIGHT信号通路相关的疾病(例如，自身免疫性疾病和/或炎症性疾病)的个体的方法，包括向所述个体施用有效量的包含抗LIGHT抗体的组合物，其中所述抗体包含：VH，所述VH包含：HC-CDR1，其包含氨基酸序列SEQ ID NO:6，HC-CDR2，其包含氨基酸序列SEQ ID NO:14，和HC-CDR3，其包含氨基酸序列SEQ ID NO:21，或 者所述VH的变体，其HC-CDRs中包含至多约5个氨基酸的取代；以及VL，所述VL包含：LC-CDR1，其包含氨基酸序列SEQ ID NO:83，LC-CDR2，其包含氨基酸序列SEQ ID NO:35，和LC-CDR3，其包含氨基酸序列SEQ ID NO:43，或者所述VL的变体，其LC-CDRs中包含至多约5个氨基酸的取代。
在一些实施例中，本文所述抗LIGHT抗体包含：VH，所述VH包含氨基酸序列SEQ ID NO:84或其变体，所述变体与氨基酸序列SEQ ID NO:84具有至少约80％序列同一性；以及VL，所述VL包含氨基酸序列SEQ ID NO:89或其变体，所述变体与氨基酸序列SEQ ID NO:89具有至少约80％序列同一性。在一些实施例中，本文所述抗LIGHT抗体是包含IgG1或IgG4恒定区的全长抗LIGHT抗体。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，本文所述抗LIGHT抗体包含：VH，所述VH包含氨基酸序列SEQ ID NO:85或其变体，所述变体与氨基酸序列SEQ ID NO:85具有至少约80％序列同一性；以及VL，所述VL包含氨基酸序列SEQ ID NO:90或其变体，所述变体与氨基酸序列SEQ ID NO:90具有至少约80％序列同一性。在一些实施例中，本文所述抗LIGHT抗体是包含IgG1或IgG4恒定区的全长抗LIGHT抗体。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，本文所述抗LIGHT抗体包含：VH，所述VH包含氨基酸序列SEQ ID NO:84或其变体，所述变体与氨基酸序列SEQ ID NO:84具有至少约80％序列同一性；以及VL，所述VL包含氨基酸序列SEQ ID NO:91或其变体，所述变体与氨基酸序列SEQ ID NO:91具有至少约80％序列同一性。在一些实施例中，本文所述抗LIGHT抗体是包含IgG1或IgG4恒定区的全长抗LIGHT抗体。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
例如，在一些实施例中，提供一种用于治疗患有与LIGHT信号通路相关的疾病(例如，自身免疫性疾病和/或炎症性疾病)的个体的方法，包括向所述个体施用有效量的包含抗LIGHT抗体(例如，全长抗LIGHT抗体)的药物组合物，其中所述抗体包含：重链可变结构域(VH)，所述VH包含：HC-CDR1，其包含氨基酸序列SEQ ID NO:7，HC-CDR2，其包含氨基酸序列SEQ ID NO:15，和HC-CDR3，其包含氨基酸序列SEQ ID NO:22，或者所述VH的变体，其HC-CDRs中包含至多约5个氨基酸的取代；以及轻链可变结构域(VL)，所述VL包含：LC-CDR1，其包含氨 基酸序列SEQ ID NO:29，LC-CDR2，其包含氨基酸序列SEQ ID NO:36，和LC-CDR3，其包含氨基酸序列SEQ ID NO:44，或者所述VL的变体，其LC-CDRs中包含至多约5个氨基酸的取代。在一些实施例中，所述抗LIGHT抗体是全长抗体。在一些实施例中，所述全长抗LIGHT抗体是IgG1或IgG4抗体。在一些实施例中，所述疾病或病症选自例如，炎性肠道疾病(IBD)、克罗恩疾病、溃疡性结肠炎、强直性脊柱炎、异位性皮炎、类风湿性关节炎、细支气管炎、移植排斥反应、同种移植排斥反应、移植物抗宿主病(GVHD)、哮喘、嗜酸性食管炎、急性呼吸窘迫综合征(ARDS)、慢性心脏衰竭、慢性阻塞性肺病(COPD)、败血性休克、纤维化疾病、皮肤纤维化、特发性肺纤维化、肾纤维化、慢性肾病、系统性硬化、多发性硬化症、斯耶格伦氏综合征、狼疮、气道炎症、银屑病、肝炎、乳糜泻、原发性胆汁肝硬化、自身免疫性溶血性贫血、自身免疫性新生儿血小板减少症、原发性血小板减少性紫癜、非酒精性脂肪肝、COVID19。在一些实施例中，所述个体是人类。
在一些实施例中，提供一种用于治疗患有与LIGHT信号通路相关的疾病(例如，自身免疫性疾病和/或炎症性疾病)的个体的方法，包括向所述个体施用有效量的包含抗LIGHT抗体的组合物，其中所述抗体包含：VH，所述VH包含SEQ ID NOs:61，92-94中任一所示的氨基酸序列或其变体，所述变体与SEQ ID NOs:61，92-94中任一所示的氨基酸序列具有至少约80％序列同一性；以及VL，所述VL包含SEQ ID NOs:73，95-99中任一所示的氨基酸序列或其变体，所述变体与SEQ ID NOs:73，95-99中任一所示的氨基酸序列具有至少约80％序列同一性。
在一些实施例中，本文所述抗LIGHT抗体是包含IgG1或IgG4恒定区的全长抗LIGHT抗体。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种用于治疗患有与LIGHT信号通路相关的疾病(例如，自身免疫性疾病和/或炎症性疾病)的个体的方法，包括向所述个体施用有效量的包含抗LIGHT抗体的组合物，其中所述抗体包含：VH，所述VH包含SEQ ID NO:61所示的氨基酸序列或其变体，所述变体与SEQ ID NO:61所示的氨基酸序列具有至少约80％序列同一性；以及VL，所述VL包含SEQ ID NO:73所示的氨基酸序列或其变体，所述变体与SEQ ID NO:73所示的氨基酸序列具有至少约80％序列同一性。在一些实施例中，本文所述抗LIGHT抗体是包含IgG1或IgG4恒定区的全长抗LIGHT抗体。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种用于治疗患有与LIGHT信号通路相关的疾病(例如，自身免疫性疾病和/或炎症性疾病)的个体的方法，包括向所述个体施用有效量的包含抗LIGHT抗体的组合 物，其中所述抗体包含：VH，所述VH包含氨基酸序列SEQ ID NO:92或其变体，所述变体与氨基酸序列SEQ ID NO:92具有至少约80％序列同一性；以及VL，所述VL包含氨基酸序列SEQ ID NO:95或其变体，所述变体与氨基酸序列SEQ ID NO:95具有至少约80％序列同一性。在一些实施例中，本文所述抗LIGHT抗体是包含IgG1或IgG4恒定区的全长抗LIGHT抗体。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种用于治疗患有与LIGHT信号通路相关的疾病(例如，自身免疫性疾病和/或炎症性疾病)的个体的方法，包括向所述个体施用有效量的包含抗LIGHT抗体的组合物，其中所述抗体包含：VH，所述VH包含氨基酸序列SEQ ID NO:93或其变体，所述变体与氨基酸序列SEQ ID NO:93具有至少约80％序列同一性；以及VL，所述VL包含氨基酸序列SEQ ID NO:96或其变体，所述变体与氨基酸序列SEQ ID NO:96具有至少约80％序列同一性。在一些实施例中，本文所述抗LIGHT抗体是包含IgG1或IgG4恒定区的全长抗LIGHT抗体。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种用于治疗患有与LIGHT信号通路相关的疾病(例如，自身免疫性疾病和/或炎症性疾病)的个体的方法，包括向所述个体施用有效量的包含抗LIGHT抗体的组合物，其中所述抗体包含：VH，所述VH包含氨基酸序列SEQ ID NO:92或其变体，所述变体与氨基酸序列SEQ ID NO:92具有至少约80％序列同一性；以及VL，所述VL包含氨基酸序列SEQ ID NO:96或其变体，所述变体与氨基酸序列SEQ ID NO:96具有至少约80％序列同一性。在一些实施例中，本文所述抗LIGHT抗体是包含IgG1或IgG4恒定区的全长抗LIGHT抗体。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种用于治疗患有与LIGHT信号通路相关的疾病(例如，自身免疫性疾病和/或炎症性疾病)的个体的方法，包括向所述个体施用有效量的包含抗LIGHT抗体的组合物，其中所述抗体包含：VH，所述VH包含氨基酸序列SEQ ID NO:94或其变体，所述变体与氨基酸序列SEQ ID NO:94具有至少约80％序列同一性；以及VL，所述VL包含氨基酸序列SEQ ID NO:97或其变体，所述变体与氨基酸序列SEQ ID NO:97具有至少约80％序列同一性。在一些实施例中，本文所述抗LIGHT抗体是包含IgG1或IgG4恒定区的全长抗LIGHT抗体。在一些实施例 中，所述IgG1是人IgG1。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种用于治疗患有与LIGHT信号通路相关的疾病(例如，自身免疫性疾病和/或炎症性疾病)的个体的方法，包括向所述个体施用有效量的包含抗LIGHT抗体的组合物，其中所述抗体包含：VH，所述VH包含氨基酸序列SEQ ID NO:94或其变体，所述变体与氨基酸序列SEQ ID NO:94具有至少约80％序列同一性；以及VL，所述VL包含氨基酸序列SEQ ID NO:98或其变体，所述变体与氨基酸序列SEQ ID NO:98具有至少约80％序列同一性。在一些实施例中，本文所述抗LIGHT抗体是包含IgG1或IgG4恒定区的全长抗LIGHT抗体。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种用于治疗患有与LIGHT信号通路相关的疾病(例如，自身免疫性疾病和/或炎症性疾病)的个体的方法，包括向所述个体施用有效量的包含抗LIGHT抗体的组合物，其中所述抗体包含：VH，所述VH包含氨基酸序列SEQ ID NO:93或其变体，所述变体与氨基酸序列SEQ ID NO:93具有至少约80％序列同一性；以及VL，所述VL包含氨基酸序列SEQ ID NO:98或其变体，所述变体与氨基酸序列SEQ ID NO:98具有至少约80％序列同一性。在一些实施例中，本文所述抗LIGHT抗体是包含IgG1或IgG4恒定区的全长抗LIGHT抗体。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种用于治疗患有与LIGHT信号通路相关的疾病(例如，自身免疫性疾病和/或炎症性疾病)的个体的方法，包括向所述个体施用有效量的包含抗LIGHT抗体的组合物，其中所述抗体包含：VH，所述VH包含氨基酸序列SEQ ID NO:92或其变体，所述变体与氨基酸序列SEQ ID NO:92具有至少约80％序列同一性；以及VL，所述VL包含氨基酸序列SEQ ID NO:98或其变体，所述变体与氨基酸序列SEQ ID NO:98具有至少约80％序列同一性。在一些实施例中，本文所述抗LIGHT抗体是包含IgG1或IgG4恒定区的全长抗LIGHT抗体。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种用于治疗患有与LIGHT信号通路相关的疾病(例如，自身免疫性疾病和/或炎症性疾病)的个体的方法，包括向所述个体施用有效量的包含抗LIGHT抗体的组合物，其中所述抗体包含：VH，所述VH包含氨基酸序列SEQ ID NO:94或其变体，所述变体与氨基酸序列SEQ ID NO:94具有至少约80％序列同一性；以及VL，所述VL包含氨基酸序列SEQ ID NO:99或其变体，所述变体与氨基酸序列SEQ ID NO:99具有至少约80％序列同一性。在一些实施例中，本文所述抗LIGHT抗体是包含IgG1或IgG4恒定区的全长抗LIGHT抗体。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，提供一种用于治疗患有与LIGHT信号通路相关的疾病(例如，自身免疫性疾病和/或炎症性疾病)的个体的方法，包括向所述个体施用有效量的包含抗LIGHT抗体的组合物，其中所述抗体包含：VH，所述VH包含氨基酸序列SEQ ID NO:92或其变体，所述变体与氨基酸序列SEQ ID NO:92具有至少约80％序列同一性；以及VL，所述VL包含氨基酸序列SEQ ID NO:99或其变体，所述变体与氨基酸序列SEQ ID NO:99具有至少约80％序列同一性。在一些实施例中，本文所述抗LIGHT抗体是包含IgG1或IgG4恒定区的全长抗LIGHT抗体。在一些实施例中，所述IgG1是人IgG1。在一些实施例中，所述IgG4是人IgG4。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:74组成。在一些实施例中，重链恒定区包含或由氨基酸序列SEQ ID NO:75组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:76组成。在一些实施例中，轻链恒定区包含或由氨基酸序列SEQ ID NO:77组成。
在一些实施例中，所述个体是哺乳动物(例如人、非人灵长类、大鼠、小鼠、牛、马、猪、绵羊、山羊、狗、猫等)。在一些实施例中，所述个体是人类。在一些实施例中，所述个体是临床患者、临床试验志愿者、实验动物等。在一些实施例中，所述个体年龄小于60岁(包括例如小于50、40、30、25、20、15或10岁)。在一些实施例中，所述个体年龄大于60岁(包括例如大于70、80、90或100岁)。在一些实施例中，所述个体是被诊断为或在遗传角度上易患本文所描述的一种或多种疾病或病症(例如自身免疫性疾病和/或炎症性疾病)。在一些实施例中，所述个体具有一种或多种与本文所述的一种或多种疾病或病症相关的风险因子。
在一些实施例中，本申请提供一种向个体中在其表面表达LIGHT的细胞递送抗LIGHT抗体(例如本文所述的任一种抗LIGHT抗体，例如分离的抗LIGHT抗体)的方法，所述方法包括向该个体施用包含抗LIGHT抗体的组合物。
自身免疫性疾病和/或炎症性疾病或其它任何表现出LIGHT异常表达的疾病的许多诊断方法和这些疾病的临床描述在本领域是已知的。这类方法包括，但不限于，例如免疫组化、PCR以及荧光原位杂交(FISH)。
在一些实施例中，本申请所述抗LIGHT抗体(例如全长抗LIGHT抗体)和/或组合物与第二、第三或第四药剂(包括例如类固醇，非类固醇消炎药(NSAIDS)(例如水杨酸类、丙酸衍生物、乙酸衍生物、烯醇酸衍生物、邻氨基苯基酸衍生物、选择性COX-2抑制剂和磺酰苯胺)，糖皮质激素(如皮质醇、可的松、强的松、泼尼松龙、地塞米松、倍他米松、曲安西龙等)，细胞抑制剂(如烷化剂、抗代谢物、甲氨蝶呤、硫唑嘌呤、巯基嘌呤或细胞毒性抗生素)，TNF抑制剂，IL-12抑制剂，IL-23抑制剂，α4β7整合素抑制剂)联合使用来治疗与LIGHT信号通路相关的疾病。
抗LIGHT抗体的给药剂量和方法
施用于个体(例如人)的抗LIGHT抗体(例如分离的抗LIGHT抗体)组合物的剂量可能因特定组合物、给药方式和治疗疾病类型的不同而不同。在一些实施例中，组合物(例如，包含抗LIGHT抗体的组合物)的量可在自身免疫性疾病和/或炎症性疾病治疗中有效产生客观响应(例如，部分响应或完全响应)。在一些实施例中，抗LIGHT抗体组合物的量足以在个体中产生完全响应。在一些实施例中，抗LIGHT抗体组合物的量足以在个体中产生部分响应。在一些实施例中，抗LIGHT抗体组合物的给药剂量(例如当单独施用时)足以在使用抗LIGHT抗体组合物治疗的个体群体中产生高于20％、25％、30％、35％、40％、45％、50％、55％、60％、64％、65％、70％、75％、80％、85％或90％的总响应率。个体对本文所述治疗方法的响应可通过，例如，ACQ5评分来确定。
在一些实施例中，组合物(例如包含分离的抗LIGHT抗体的组合物)的量足以延长个体的无进展生存期。在一些实施例中，组合物的量足以延长个体的总体生存期。在一些实施例中，在使用抗LIGHT抗体组合物治疗的个体群体中，组合物的量(例如当单独施用时)足以产生高于50％、60％、70％或77％的临床益处。
在一些实施例中，组合物(例如包含分离的抗LIGHT抗体的组合物)的量，单独使用或与第二，第三、和/或第四药剂联合使用时，是指在治疗前或与未接受治疗的其他受试者的相应活性相比，足以控制症状和减少病情加重的风险的量。可以采用标准方法来测量该疗效的大小，例如纯化酶的体外检测、基于细胞的检测、动物模型或人体试验。
在一些实施例中，当将组合物施用于个体时，组合物中抗LIGHT抗体(例如全长的抗LIGHT抗体)的量低于引起毒性效应(即，一种高于临床可接受毒性水平的效应)的水平，或者处于潜在副作用可以控制或耐受的水平。
在一些实施例中，遵循相同的给药方案，组合物的量接近的组合物的最大耐受剂量(MTD)。在一些实施例中，组合物的量高于MTD的80％、90％、95％或98％。
在一些实施例中，组合物中抗LIGHT抗体(例如全长的抗LIGHT抗体)的含量在0.001μg到1000μg的范围之内。
在如上所述任一个实施例中，组合物中的抗LIGHT抗体(例如全长的抗LIGHT抗体)的有效量，按照体重时计算，为0.1μg/kg到100mg/kg的范围之内。
抗LIGHT抗体组合物可通过多种途径施用于个体(如人类)，包括，例如静脉注射、动脉内给药、腹腔注射、肺内给药、口服给药、吸入给药、血管内给药、肌肉注射、气管内给药、皮下注射、眼内给药、鞘内给药、粘膜给药或经皮给药。在一些实施例中，使用组合物的缓释制剂。在一些实施例中，组合物通过静脉给药。在一些实施例中，组合物通过动脉给药。在一些实施例中，组合物通过腹膜内给药。在一些实施例中，组合物通过肝内给药。在一些实施例中，组合物通过肝动脉输注给药。在一些实施例中，组合物施用于远离第一病灶的部位。
制品及试剂盒
在本申请的一些实施例中，提供一种制品，所述制品包含一种物质，所述物质能够用于治疗与LIGHT信号通路相关的疾病(例如，自身免疫性疾病和/或炎症性疾病)，或者用于递送抗LIGHT抗体(例如一种全长抗LIGHT抗体)到表面表达LIGHT的细胞。所述制品可以包括一种容器以及在容器上或随该容器附带的标签或包装说明书。合适的容器包括，例如瓶子、小瓶、注射器等。容器可以由多种材料制成，例如玻璃或塑料。通常，该容器内装有能够有效治疗本文所述疾病或病症的组合物，并且具有一个无菌端口(例如该容器可以是一个静脉输液袋或是一个具有皮下注射针头可刺穿盖子的小瓶)。组合物中的至少一种活性物质即为本申请所述的抗LIGHT抗体。标签或包装说明书标示了该组合物可以用于治疗的特定病症。标签或包装说明书进一步包含给患者施用抗LIGHT抗体组合物的说明书。包括联合治疗的制品和试剂盒均在本文的考虑范围之内。
包装说明书是指通常包含在治疗产品的商业包装内的说明书，其包含关于与这些治疗产品使用有关的适应症、用法、剂量、施用、禁忌症和/或警告信息。在一些实施例中，包装说明书标明该组合物可以用于治疗与LIGHT信号通路相关的疾病(例如自身免疫性疾病和/或炎症性疾病)。在一些实施例中，包装说明书标明该组合物可以用于治疗以下的疾病，包括炎性肠道疾病(IBD)、克罗恩疾病、溃疡性结肠炎、强直性脊柱炎、异位性皮炎、类风湿性关节炎、细支气管炎、移植排斥反应、同种移植排斥反应、移植物抗宿主病(GVHD)、哮喘、嗜酸性食管炎、急性呼吸窘迫综合征(ARDS)、慢性心脏衰竭、慢性阻塞性肺病(COPD)、败血性休克、纤维化疾病、皮肤纤维化、特发性肺纤维化、肾纤维化、慢性肾病、系统性硬化、多发性硬化症、斯耶格伦氏综合征、狼疮、气道炎症、银屑病、肝炎、乳糜泻、原发性胆汁肝硬化、自身免疫性溶血性贫血、自身免疫性新生儿血小板减少症、原发性血小板减少性紫癜、非酒精性脂肪肝、COVID19。
此外，所述制品还可以包括第二容器，其包含药学上可接受的缓冲液，例如抑菌性注射用水(BWFI)、磷酸盐缓冲液、格林氏溶液或葡萄糖溶液。还可以包括从商业和用户角度而言所需的其他材料，包括其他缓冲液、稀释液、过滤器、针头和注射器。
同时还涉及可用于各种目的的试剂盒，例如用于治疗与LIGHT信号通路相关的疾病(例如自身免疫性疾病和/或炎症性疾病)，或者用于递送抗LIGHT抗体(例如全长抗LIGHT抗体)到表面表达LIGHT的细胞中，任选与制品组合。本申请的试剂盒包括一个或多个容器，其包含抗 LIGHT抗体组合物(或单剂量形式和/或制品)，并且在一些实施例中，进一步包含另一种药剂(例如本文所述的药剂)和/或与本文所述任一方法相一致的使用说明书。该试剂盒可进一步包括选择适合治疗个体的描述。本申请中试剂盒中所附带的使用说明书通常是标签或包装说明书上的书面说明(例如包含在试剂盒内的纸页)，机器可读的说明(例如，磁性或光学储存光盘上的说明)也是可以接受的。
例如，在一些实施例中，试剂盒包括一种包含抗LIGHT抗体(例如全长的抗LIGHT抗体)的组合物。在一些实施例中，试剂盒包括：a)包含本文所述的任一种抗LIGHT抗体的组合物，和b)至少一种有效量的其它药剂，其能够增强抗LIGHT抗体的效果(如治疗效果、检测效果)。在一些实施例中，试剂盒包括：a)包含本文所述的任一种抗LIGHT抗体的组合物，和b)向个体施用抗LIGHT抗体组合物用于治疗与LIGHT信号通路相关的疾病(例如自身免疫性疾病和/或炎症性疾病)的使用说明书。在一些实施例中，试剂盒包括：a)包含本文所述的任一种抗LIGHT抗体的组合物，和b)至少一种有效量的其它药剂，其能够增强抗LIGHT抗体的效果(如治疗效果、检测效果)和c)向个体施用抗LIGHT抗体组合物和其它物质用于治疗与LIGHT信号通路相关的疾病(例如自身免疫性疾病和/或炎症性疾病)的使用说明书。所述抗LIGHT抗体和其他物质可以存在于独立的容器或同一个容器中。例如，该试剂盒可以包括一种特定组合物或两种或更多种组合物，其中一种组合物包括抗LIGHT抗体，另一种组合物包括另一种药剂。
在一些实施例中，试剂盒包含一种(或一组)编码抗LIGHT抗体(例如全长的抗LIGHT抗体)的核酸。在一些实施例中，试剂盒包含：a)一种(或一组)编码抗LIGHT抗体(例如全长的抗LIGHT抗体)的核酸，和b)一种表达核酸(或一组核酸)的宿主细胞。在一些实施例中，试剂盒包含：a)一种(或一组)编码抗LIGHT抗体(例如全长的抗LIGHT抗体)的核酸，和b)使用说明书，适用于：i)在宿主细胞中表达抗LIGHT抗体，ii)制备包含抗LIGHT抗体的组合物，和iii)向个体施用包含抗LIGHT抗体的组合物来治疗与LIGHT信号通路相关的疾病(例如自身免疫性疾病和/或炎症性疾病)。在一些实施例中，试剂盒包括：a)一种(或一组)编码抗LIGHT抗体(例如全长的抗LIGHT抗体)的核酸，b)一种表达核酸(或一组核酸)的宿主细胞，和c)使用说明书，适用于：i)在宿主细胞中表达抗LIGHT抗体，ii)制备包含抗LIGHT抗体的组合物，和iii)向个体施用包含抗LIGHT抗体的组合物来治疗与LIGHT信号通路相关的疾病(例如自身免疫性疾病和/或炎症性疾病)。
本申请所述的试剂盒以合适的形式进行包装。合适的包装包括，但不限于，小瓶、瓶子、广口瓶、软包装(例如密封的聚酯薄膜或塑料袋)等。试剂盒可以任选地提供其它的组分，例如缓冲液和说明信息。因此，本申请还提供制品，其包括小瓶、瓶子、广口瓶、软包装(例如密封的聚酯薄膜或塑料袋)等。
关于抗LIGHT抗体组合物的使用说明书，通常包括一些信息，诸如，剂量，给药周期和给药途径等。容器可以是单位剂量的，大包装的(如，多剂量包装)或亚单位剂量的。例如，提供一种包含足够剂量的如本文所述的抗LIGHT抗体(例如全长的抗LIGHT抗体)的试剂盒以对个体进 行长期有效的治疗，例如一周、8天、9天、10天、11天、12天、13天、2周、3周、4周、6周、8周、3个月、4个月、5个月、7个月、8个月、9个月或更长时间。试剂盒还可包含多单位剂量的抗LIGHT抗体、药物组合物和使用说明书，并且以足够在药房中储存和使用的量进行包装，例如，医院药房和复方药房。
本领域的技术人员将认识到在本申请的范围和宗旨内可能的若干实施例。现在将通过参考以下非限制性实施例来更详细地描述本申请。以下实施例进一步阐明本申请，但不应解释为以任何方式进行限制其范围。
具体实施方式
在下述公开的实施例中，适用如下缩写：LIGHT(别称TNFSF14，tumor necrosis factor superfamily member 14，肿瘤坏死因子超家族14)；HVEM(herpes virus entry mediator，单纯疱疹病毒进入介导子，别称TNFRSF14,CD270)；LTβR(lymphotoxinβreceptor，淋巴毒素β受体)。
实施例1：制备抗原重组蛋白
制备重组LIGHT衍生多肽
通过亚克隆将编码人、食蟹猴或小鼠LIGHT的cDNA分别构建到哺乳动物细胞表达载体中。在上述cDNA的N端添加His标签和/或Fc标签和/或本领域技术人员常用的其它标签，构建并表达出含有人、食蟹猴或小鼠LIGHT的融合蛋白，例如His-人LIGHT(His-huLIGHT，SEQ ID NO：79)、hFc-人LIGHT(hFc-huLIGHT，SEQ ID NO：80)、His-食蟹猴LIGHT(His-cynoLIGHT，SEQ ID NO：81)、His-小鼠LIGHT(His-musLIGHT，SEQ ID NO：82)。其中，“His”代表His标签，“hFc”代表人IgG1抗体Fc段。
对上述重组LIGHT蛋白，包括hFc-huLIGHT、His-huLIGHT、His-cynoLIGHT、His-musLIGHT，进行表达纯化。简言之，将含有上述融合蛋白基因的表达载体质粒分别转染293F细胞，并将上述细胞在37℃、5％CO2、120rpm条件下培养5天，随后收集细胞培养液。
根据制造商的操作说明，采用镍柱(Ni)纯化具有His标签的重组蛋白。具体操作如下：采用常州天地人和生物技术有限公司的Ni-NTA(5ml)进行固定化金属亲和层析(IMAC)。首先采用缓冲液A1(1×PBS、pH 7.4)平衡镍柱，流速150cm/h，将培养液上清的pH调整至7.2-7.4，室温上样，流速5ml/min。随后，采用6倍柱体积的A1缓冲液再次平衡该柱，流速5ml/min。随后，采用6倍柱体积的A2缓冲液(含30mM咪唑的1×PBS、pH 7.4)洗杂，流速5ml/min，最后采用10倍柱体积的B缓冲液(包含0.25M咪唑的1×PBS，pH 7.4)进行洗脱，收集洗脱液，用合适截留分子量的超滤管浓缩换液至PBS。
根据制造商的操作说明，采用Protein A亲和层析柱纯化具有Fc标签的重组蛋白。具体操作如下：首先采用6倍柱体积PBS缓冲液(包含0.15M NaCl，pH7.4)以150cm/h(流速5ml/min)的流速平衡蛋白A柱。培养液上清(调节pH至7.2-7.4)以150cm/h(流速5ml/min)流速流穿柱子。进一步平衡该柱后，采用6倍柱体积的0.1M甘氨酸缓冲液(含0.15M NaCl，pH3.2)洗脱，收集 洗脱液，调节pH值至中性。利用超滤浓缩管将目的蛋白溶液置换于PBS缓冲液中，超滤浓缩后采用BCA蛋白定量试剂盒测定目的蛋白浓度。
筛选抗LIGHT单链抗体(scFv)
构建scFv抗体噬菌体展示文库：使用His-huLIGHT作为抗原，与等份(v/v)佐剂一起免疫6-8周龄BALB/c小鼠。收集免疫后的小鼠血清，ELISA法检测免疫后小鼠血清中的总IgG滴度。几轮免疫后，使用小鼠脾脏建立噬菌体展示库。简言之，取免疫后的小鼠脾脏，提取RNA，经逆转录获得cDNA，采用VH和VK特异性引物扩增VH和VK片段，经过胶回收纯化后，连接VH和VK，构建scFv，并将其克隆到噬菌体展示载体pDAN3X中，连接后转化TG1噬菌体展示电穿孔感受态细胞，以获得scFv抗体噬菌体展示文库。
筛选抗LIGHT单链抗体(scFv)：采用固相筛选策略从上述噬菌体展示文库中分离特异性结合人LIGHT的噬菌体。简言之，将His-huLIGHT或hFc-huLIGHT包被于酶标板中，每孔加入4×1011pfu噬菌体展示文库，37℃孵育2小时。洗板后，采用酸性洗脱液洗脱特异性结合人LIGHT的阳性噬菌体。如此经过3轮重复筛选后，进一步通过ELISA法检测单个阳性克隆与人LIGHT的结合情况。对多轮筛选后的阳性scFv进行测序，获得候选先导抗体序列。候选先导抗体的重链和轻链的可变结构域序列如表2和表3所示。
实施例2：制备和表征全长的抗LIGHT抗体
制备抗LIGHT全长抗体
将测序得到的来源于鼠的抗LIGHT抗体的VL和VH序列，分别构建入真核表达载体pTTa1-L(包含κ恒定区)和pTTa1-H4(包含人IgG4重链恒定区)中。将分别提取的表达轻链或重链的质粒，共转染293F细胞，37℃、8％CO2、120rpm培养6天。
用蛋白A亲和层析柱纯化培养液。简言之，首先采用6倍柱体积的PBS缓冲液(包含0.15M NaCl，pH7.4)以5ml/min的流速平衡蛋白A柱。培养液上清(调节pH至7.2-7.4)以5ml/min流速流穿柱子。进一步平衡该柱后，采用6倍柱体积的0.1M甘氨酸缓冲液(含0.15M NaCl，pH3.2)洗脱，收集洗脱液，调节pH值至中性。利用脱盐柱将IgG溶液置换于PBS缓冲液中，超滤浓缩后测定IgG浓度，获得全长的嵌合抗LIGHT抗体。
ELISA法检测抗LIGHT抗体的结合活性
ELISA结合试验：将纯化后的嵌合抗体与人LIGHT蛋白进行结合试验，用于鉴定候选嵌合抗LIGHT抗体与人LIGHT的结合活性。简言之，将纯化的His-huLIGHT溶解在PBS溶液中，按照0.1μg/孔包被至96孔板，4℃孵育过夜，PBST溶液洗涤6次。加入1％BSA(PBS溶解)封闭液，37℃封闭1小时，PBST溶液洗涤6次。随后加入100μl/孔梯度稀释的待测抗LIGHT抗体(起始浓度为100μg/ml，再作1:3梯度稀释)，其中F19作为阳性对照抗体，37℃孵育1小时，PBST溶液洗涤6次。随后各孔加入100μl山羊抗人IgG-HRP二抗(1:20000稀释)，37℃孵育1小时，PBST溶液洗涤6次。每孔加入100μl TMB显色，37℃避光孵育5-10分钟，用2M H2SO4终止反应。测定OD450nm，并通过GraphPad Prism 5.0生成结合曲线，计算各候选抗体与抗原His-huLIGHT结合 的EC50值。
结果如图1和表5所示，嵌合抗LIGHT抗体LT-m17、LT-m18(图1A)、LT-m31、LT-m 33、LT-m37(图1B)、LT-m55、LT-m58、LT-m64、LT-m85(图1C)能够有效结合人LIGHT抗原，其结合活性优于阳性对照抗体F19(Cerecor公司)，或与之相当。
表5：抗LIGHT抗体与人LIGHT的结合活性
ELISA法检测抗LIGHT抗体阻断LIGHT与LTβR结合的活性
通过ELISA法检测抗LIGHT抗体阻断LIGHT与其受体LTβR结合的活性，以IC50值作为衡量候选嵌合抗体中和活性的标准。简言之，将100ng/孔的人LTβR-His(来自舒泰神)包被至96孔板，4℃过夜，PBST溶液洗涤6次。加入1％BSA(PBS溶解)封闭液，37℃封闭1小时，PBST溶液洗涤6次。随后加入50μl/孔梯度稀释的待测抗LIGHT抗体(起始浓度为100μg/ml，1：3梯度稀释)，其中F19作为阳性对照抗体，之后立即加入50μl浓度为1μg/ml纯化的hFc-huLIGHT，37℃孵育1小时，PBST溶液洗涤后，向各孔中加入100μl山羊抗人IgG-HRP二抗(1:20000稀释)，37℃孵育1小时。最后每孔加入100μl TMB显色，37℃避光孵育5-10分钟，用2M H2SO4终止反应。测定OD450nm，并通过GraphPad Prism 5.0生成结合曲线，计算IC50值，并以F19抗体作为基准计算IC50的比值(各候选抗体的IC50/F19抗体的IC50)。
结果如表6所示，嵌合抗LIGHT抗体LT-m17、LT-m18、LT-m31、LT-m33、LT-m37、LT-m55、LT-m58、LT-m64、LT-m85能够有效地阻断LIGHT与其受体LTβR的结合，其中和活性均优于阳性对照抗体F19。
表6：抗LIGHT抗体抑制人LIGHT结合人LTβR的活性

ELISA法检测抗LIGHT抗体阻断LIGHT与HVEM结合的活性
LIGHT不仅与LTβR受体结合，还与HVEM受体结合。通过ELISA法检测候选嵌合抗LIGHT抗体阻断LIGHT与其受体HVEM结合的活性。具体方法按照上述“ELISA法检测抗LIGHT抗体阻断LIGHT与LTβR结合的活性”所述方案进行，其中包被蛋白为HVEM-His(来自舒泰神)。
结果如表7所示，示例性嵌合抗LIGHT抗体LT-m17、LT-m18、LT-m31、LT-m33、LT-m37能够有效地阻断LIGHT与其受体HVEM的结合，其中和活性均优于阳性对照抗体F19。
表7：抗LIGHT抗体抑制人LIGHT结合人HVEM活性
抗LIGHT抗体的种属交叉活性检测/
采用ELISA法检测候选嵌合抗LIGHT抗体与食蟹猴LIGHT、小鼠LIGHT的交叉结合活性，具体方法按照上述“ELISA法检测抗LIGHT抗体的结合活性”方案进行，其中包被的抗原为纯化的His-cynoLIGHT或His-musLIGHT蛋白。
与食蟹猴LIGHT的交叉结合活性结果如图2所示，嵌合抗LIGHT抗体LT-m17、LT-m18(图2A)、LT-m31、LT-m33、LT-m37(图2B)、LT-m55、LT-m58、LT-m64、LT-m85(图2C)与食蟹猴LIGHT均有较强的交叉结合活性。
候选嵌合抗LIGHT抗体LT-m17、LT-m18、LT-m31、LT-m33、LT-m37与小鼠LIGHT有弱交叉结合活性，其他嵌合抗体与小鼠LIGHT无交叉结合活性(数据未显示)。
BIAcore法测定抗LIGHT抗体的亲和力
采用Biacore 8K(GE)表征抗LIGHT抗体与人LIGHT、食蟹猴LIGHT的结合亲和力。将抗LIGHT抗体固定于传感器芯片CM5上，检测不同浓度的抗体与不同种属LIGHT的亲和力，用SPR技术测量抗体的结合速率和解离速率，并确定结合亲和力。
抗LIGHT抗体的Kon、Koff以及Kd值如表8所示，由此可见，示例性嵌合抗LIGHT抗体LT-m31、LT-m33、LT-m55、LT-m58、LT-m64、LT-m85以高亲和力结合人LIGHT抗原。
示例性嵌合抗LIGHT抗体LT-m17、LT-m18、LT-m55、LT-m58、LT-m64、LT-m85与食蟹猴LIGHT也具有较强的交叉结合活性。
表8：Biacore法检测抗NKG2A抗体的亲和力
抗LIGHT抗体抑制人LIGHT激活LTβR报告基因的活性检测/
LIGHT结合LTβR受体后，能够激活NF-κB通路。采用构建的LTβR受体激动响应的荧光素酶报告基因细胞系(Hela-Rc32-NF-κB-Luc)，来检测嵌合抗LIGHT抗体对LIGHT(包括游离LIGHT和细胞表面LIGHT)激活LTβR受体而启动荧光素酶信号的抑制能力，以作为候选嵌合抗LIGHT抗体对LIGHT激活LTβR介导信号通路的抑制作用的衡量指标。
游离的LIGHT激活报告基因的实验：
首先构建LTβR受体激动响应的荧光素酶报告基因细胞系(Hela-Rc32-NF-κB-Luc)。简言之，子宫颈癌细胞系Hela-Rc32表达LTβR受体，又因为LIGHT结合LTβR后激活NF-κB通路，因此将质粒pGL4.32[luc2P/NF-κB-RE/Hygro](Promega,Cat#E849A)转染Hela-Rc32细胞系，其中该质粒的荧光素酶基因位于NF-κB响应元件下游，当LIGHT结合LTβR后就能激活荧光素酶。
构建方法如下：按照制造商的操作说明书，采用3000试剂(Invitrogen，货号L3000-001)将质粒载体pGL4.32[luc2P/NF-κB-RE/Hygro](Promega,Cat#E849A)转染至Hela-Rc32细胞(ATCC，CRL-2972)，并在含有抗生素的完全培养基(DMEM，10％FBS，400μg/ml Hygromycin B，1％Penicillin-Streptomycin简记PS)中培养，进行单克隆细胞筛选。随后挑选单克隆细胞，以1×104细胞/孔接种至白色透明底96孔板，加入50ng纯化的His-huLIGHT蛋白和200μl完全培养基，于37℃、5％CO2条件下孵育24小时。之后每孔加入100μl荧光素酶底物，避光孵育5分钟后检测荧光(RLU)，选择RLU值＞1000，或者RLU净增率(LIGHT刺激：对照)≥4的单克隆细胞扩大培养继续筛选。经过3轮重复筛选，获得Hela-Rc32-NF-κB-Luc荧光素酶报告基因细胞系。
然后将LTβR受体激动响应的荧光素酶报告基因细胞系Hela-Rc32-NF-κB-Luc以1×104细胞/孔的密度接种至白色透明底96孔板，于200μl完全培养基(DMEM，10％FBS，400μg/ml Hygromycin  B，1％PS)、37℃、5％CO2条件下培养过夜。去除细胞培养液后，加入浓度为400ng/ml的His-huLIGHT抗原50μl/孔，以及梯度稀释的待测嵌合抗LIGHT抗体(起始浓度为200μg/ml，再作1：3梯度稀释)50μl/孔，其中F19抗体作为阳性对照。轻微震荡混匀后于37℃、5％CO2条件下培养6小时。接着，采用ONE-GloTM Luciferase Assay System(Promega，货号E6120)检测方法，向平衡至室温的报告基因细胞中加入50μl ONE-GloTM缓冲液，避光震荡10分钟后，立即用酶标仪检测荧光读数(Luminescence 1000ms)。使用GraphPad Prism 5.0生成信号强度-抗体浓度曲线，计算各候选嵌合抗体抑制游离LIGHT激活LTβR-NF-κB信号的IC50值。
结果如图3所示，示例性嵌合抗LIGHT抗体LT-m17、LT-m31、LT-m33、LT-m37(图3A)、LT-m55、LT-m58、LT-m64、LT-m85(图3B)对游离LIGHT激活LTβR启动的荧光素酶信号能够进行有效地抑制，且该抑制活性优于阳性对照抗体F19，或与之相当。
细胞表面LIGHT激活报告基因的实验：
首先构建表达LIGHT的稳转细胞系(HEK293-LIGHT)。构建方法如下：按照制造商的操作说明书，采用2000试剂(Invitrogen，货号11668-027)，将表达LIGHT的质粒(来自于舒泰神)转染至HEK293细胞，并在含有抗生素的完全培养基(DMEM，10％FBS，300μg/ml Zeocin，1％PS)中培养，进行单克隆筛选并扩大培养。
选择10个左右单克隆进行细胞表面LIGHT的标记，首先向细胞中加入20μg/mL的抗LIGHT抗体F23-hFc(Cerecor公司)，4℃孵育1h，DPBS缓冲液清洗细胞3次，加入山羊抗人Fc-FITC二抗(SouthernBiotech，2063-02，1:1000稀释)，4℃避光孵育1h，DPBS清洗细胞3次。随后采用流式细胞仪检测荧光，分选收集LIGHT阳性细胞。
之后对选择的LIGHT阳性细胞株进行ELISA鉴定，简言之，将4×104细胞/孔的上述LIGHT阳性细胞接种至96孔板，37℃、5％CO2培养过夜，0.1％PBST缓冲液清洗后，每孔加入100μL 1％BSA溶液，37℃封闭30分钟，随后加入梯度浓度的抗LIGHT抗体F23-IgG4(Cerecor公司)，37℃孵育1小时，清洗后加入抗人Fc-AP二抗和显色剂PNPP，酶标仪读取OD405nm值，最终获得HEK293-LIGHT稳转细胞株。
然后将LTβR受体激动响应的荧光素酶报告基因细胞系Hela-Rc32-NF-κB-Luc以1×104细胞/孔的密度接种至白色透明底96孔板，37℃、5％CO2培养过夜。去除细胞培养液后，加入密度为2×105细胞/ml的HEK293-LIGHT稳转细胞株悬液50μl/孔，以及梯度稀释的待测嵌合抗LIGHT抗体(起始浓度为1600μg/ml，作1：3梯度稀释)50μl/孔，其中F19抗体作为阳性对照。轻微震荡混匀后于37℃、5％CO2条件下培养6小时。接着，使用ONE-GloTM Luciferase Assay System检测方法，检测荧光读数(Luminescence 1000ms)，具体方法如上所述。
结果如图4所示，示例性嵌合抗LIGHT抗体LT-m17、LT-m31、LT-m33、LT-m37(图4A)、LT-m55、LT-m58、LT-m64(图4B)、LT-m85(图4C)对细胞表面的LIGHT激活LTβR启动荧光素酶信号能够进行有效地抑制，且该抑制活性优于阳性对照抗体F19。
抗LIGHT抗体抑制人LIGHT激活HVEM报告基因的活性检测/
除了LTβR，LIGHT还与HVEM受体结合。LIGHT与HVEM结合后，同样能够激活NF-κB信号通路。通过构建的HVEM受体激动响应的荧光素酶报告基因细胞系(293T-HVEM-NF-κB-Luc)，使得LIGHT结合HVEM后能激活荧光素酶，来检测抗LIGHT抗体对游离LIGHT激活HVEM受体启动荧光素酶信号的抑制作用，作为候选嵌合抗体抑制LIGHT激活HVEM介导信号通路活性的衡量指标。
首先构建HVEM受体激动响应的荧光素酶报告基因细胞系(293T-HVEM-NF-κB-Luc)。简言之，按照制造商的操作说明书，采用慢病毒包装系统，将编码HVEM-GFP-Blasticidin融合蛋白的核酸序列构建于慢病毒载体穿梭质粒(来自舒泰神)，包装出重组慢病毒。随后将293T细胞接种至24孔板，5×104细胞/孔，弃上清后，按照不同的感染比例(1、2.5、5MOI)加入上述重组慢病毒，补加包含20％FBS的DMEM培养基至1.2ml，37℃、5％CO2培养72小时。接着更换为包含10μg/ml Blasticidin的培养基培养并筛选，10～14天后用流式细胞仪分选收集GFP荧光信号阳性(前20％的强信号)的细胞。随后将表达荧光素酶的质粒pGL4.32[luc2P/NF-κB-RE/Hygro](Promega,Cat#E849A)转染上述GFP阳性细胞，接着用流式细胞仪分选收集GFP阳性细胞，之后在包含抗生素的完全培养基(DMEM，300μg/ml Hygromycin B，10μg/ml Blasticidin，1％PS)中筛选单克隆，经扩大培养后获得HVEM受体激动响应的荧光素酶报告基因细胞系293T-HVEM-NF-κB-Luc。
然后将HVEM受体激动响应的荧光素酶报告基因细胞系293T-HVEM-NF-κB-Luc以1×104细胞/孔的密度接种至白色透明底96孔板，于200μl完全培养基(DMEM，10％FBS，300μg/ml Hygromycin B，10μg/ml Blasticidin，1％PS)、37℃、5％CO2条件下培养过夜。去除细胞培养液后，加入浓度为400ng/ml的His-huLIGHT抗原50μl/孔，以及梯度稀释的待测嵌合抗LIGHT抗体(起始浓度为至200μg/ml，再作1:3梯度稀释)50μl/孔，其中F19抗体作为阳性对照。轻微震荡混匀后于37℃、5％CO2条件下培养6小时。采用如上所述的ONE-GloTM Luciferase Assay System检测方法检测荧光值。使用GraphPad Prism 5.0生成信号强度-抗体浓度曲线，计算各候选嵌合抗体对游离LIGHT激活HVEM-NF-κB信号的抑制活性的IC50值。
结果如图5和表9所示，示例性嵌合抗LIGHT抗体LT-m17、LT-m31、LT-m33、LT-m37(图5A和表9)、LT-m55、LT-m64、LT-m85(图5B和表9)、LT-m58(图5C)对游离的LIGHT激活HVEM启动荧光素酶信号能够进行有效地抑制，且该抑制活性与阳性对照抗体F19相当。
表9：抗LIGHT抗体抑制游离的LIGHT激活HVEM报告基因的活性

实施例3:抗LIGHT抗体的人源化
分别以获得的嵌合抗体LT-m37的VH/VL的CDR典型结构为基础，将重、轻链的可变区序列与抗体种系数据库中的序列进行比较，获得同源性高的人种系模板。将小鼠抗体的CDR区移植到选定的人种系模板上以产生人源化的可变区，再与相应的人IgG恒定区(优选为IgG4重链和κ轻链)重组。随后，以小鼠抗体的三维结构为基础，对包埋残基、与CDR区有直接相互作用的残基以及对VL和VH的构象有重要影响的残基进行回复突变，并优化CDR区化学不稳定的氨基酸残基，从而分别得到最终的人源化分子hum_LT-m37-1～hum_LT-m37-16。人源化抗体的重链和轻链的可变结构域序列如表2和表3所示。
按照如上所述的人源化方法，同样对嵌合抗体LT-m58进行人源化，并且还进一步优化了CDR区域的风险点，从而获得相应的人源化分子hum_LT-m58-1～hum_LT-m58-6。上述人源化抗体的重链和轻链的可变结构域序列如表2A和表3A所示。
按照如上所述的人源化方法，同样对嵌合抗体LT-m85进行人源化改造，从而获得相应的人源化分子hum_LT-m85-1～hum_LT-m85-9。上述人源化抗体的重链和轻链的可变结构域序列如表2B和表3B所示。
实施例4:人源化抗体的表征
采用实施例2中的相应的实验方案，分别检测人源化抗LIGHT抗体的亲和力和生物活性，包括亲和力检测、中和活性检测以及生物活性检测。
ELISA法检测人源化抗LIGHT抗体的结合活性
采用实施例2所述的“ELISA法检测抗LIGHT抗体的结合活性”方案，检测人源化后的抗体(人IgG4形式)与人LIGHT的结合能力。
来源于嵌合抗体LT-m37的人源化分子结合活性的结果如图6和表10A-10B所示，人源化抗LIGHT抗体均能够有效结合人LIGHT抗原，其结合活性优于阳性对照抗体F19，或与之相当。
表10A：人源化抗LIGHT抗体与人LIGHT的结合活性

表10B：人源化抗LIGHT抗体与人LIGHT的结合活性
来源于嵌合抗体LT-m58的人源化分子结合活性的结果如表10C所示，人源化抗LIGHT抗体hum_LT-m58-1～hum_LT-m58-6均能够有效结合人LIGHT抗原，其结合活性优于阳性对照抗体F19，或与之相当。
表10C：LT-m58的人源化抗LIGHT抗体与人LIGHT的结合活性
来源于嵌合抗体LT-m85的人源化分子结合活性的结果如表10D所示，人源化抗LIGHT抗体hum_LT-m85-1～hum_LT-m85-9均能够有效结合人LIGHT抗原，其结合活性优于阳性对照抗体F19。
表10D：LT-m85的人源化抗LIGHT抗体与人LIGHT的结合活性
ELISA法检测人源化抗LIGHT抗体阻断LIGHT与LTβR结合的活性
采用实施例2所述的“ELISA法检测抗LIGHT抗体阻断LIGHT与LTβR结合的活性”方案，检测人源化后的抗LIGHT抗体(人IgG4形式)阻断LIGHT与LTβR结合的活性，以衡量人源化抗LIGHT抗体对LIGHT介导的促炎机制的抑制能力。
结果如图7和表11A-11B所示，来源于嵌合抗体LT-m37的人源化抗LIGHT抗体均能够有效阻断人LIGHT与LTβR的结合，其阻断活性优于阳性对照抗体F19。
另外，与嵌合抗体LT-m37相比，示例性人源化抗LIGHT抗体hum_LT-m37-13、hum_LT-m37-14、hum_LT-m37-15、hum_LT-m37-16(图7C和表11B)对人LIGHT与LTβR结合表现出与之相当的阻断活性。
表11A：人源化抗LIGHT抗体抑制人LIGHT结合人LTβR活性
表11B：人源化抗LIGHT抗体抑制人LIGHT结合人LTβR活性
来源于嵌合抗体LT-m58的人源化分子中和活性的结果如表11C所示，人源化抗LIGHT抗体hum_LT-m58-1～hum_LT-m58-6均能够有效阻断人LIGHT与LTβR的结合，其阻断活性优于阳性对照抗体F19。
表11C：LT-m58的人源化抗LIGHT抗体抑制人LIGHT结合人LTβR活性
来源于嵌合抗体LT-m85的人源化分子中和活性的结果如表11D所示，人源化抗LIGHT抗体 hum_LT-m85-1～hum_LT-m85-9均能够有效阻断人LIGHT与LTβR的结合，其阻断活性优于阳性对照抗体F19。
表11D：LT-m85的人源化抗LIGHT抗体抑制人LIGHT结合人LTβR活性
人源化抗LIGHT抗体的种属交叉活性检测/
采用实施例2所述的ELISA方法，检测人源化后的抗体(人IgG4形式)与食蟹猴LIGHT、小鼠LIGHT的种属交叉结合活性。
结果如表12A所示，来源于嵌合抗体LT-m37的人源化抗LIGHT抗体与食蟹猴LIGHT均有较强的交叉结合活性。
人源化抗LIGHT抗体与小鼠LIGHT有弱交叉或不交叉结合活性(数据未显示)。
表12A：抗LIGHT抗体与食蟹猴LIGHT的交叉结合能力
来源于嵌合抗体LT-m58的人源化分子的种属交叉结合活性的结果如表12B所示，示例性抗LIGHT抗体hum_LT-m58-5、hum_LT-m58-6与食蟹猴LIGHT有较强的交叉结合活性。与小鼠LIGHT没有交叉结合活性(数据未展示)。
表12B：LT-m58的人源化抗LIGHT抗体与食蟹猴LIGHT的交叉结合能力
来源于嵌合抗体LT-m85的人源化分子的种属交叉结合活性的结果如表12C所示，示例性抗LIGHT抗体hum_LT-m85-1、hum_LT-m85-2、hum_LT-m85-3、hum_LT-m85-4与食蟹猴LIGHT有较强的交叉结合活性。与小鼠LIGHT没有交叉结合活性(数据未展示)。
表12C：LT-m85的人源化抗LIGHT抗体与食蟹猴LIGHT的交叉结合能力
BIAcore法测定人源化抗LIGHT抗体的亲和力
采用Biacore 8K(GE)表征人源化抗LIGHT抗体与人LIGHT的结合亲和力。将抗LIGHT抗体固定于传感器芯片CM5上，检测不同浓度的待测人源化抗LIGHT抗体(IgG4形式)与人LIGHT的亲和力，用SPR技术测量抗体的结合速率和解离速率，并确定结合亲和力。
抗LIGHT抗体的Kon、Koff以及Kd值如表13所示，由此可见，示例性人源化抗LIGHT抗体hum_LT-m37-4、hum_LT-m37-5、hum_LT-m37-6、hum_LT-m37-7、hum_LT-m37-8、hum_LT-m37-9、hum_LT-m37-11、hum_LT-m37-12以高亲和力结合人LIGHT抗原。
表13：Biacore法检测人源化抗LIGHT抗体的亲和力
人源化抗LIGHT抗体抑制游离的LIGHT激活LTβR报告基因的活性检测/
采用实施例2所述的“抗LIGHT抗体抑制人LIGHT激活LTβR报告基因的活性检测”的实验 方案，检测人源化后的抗LIGHT抗体对游离的LIGHT激活LTβR介导信号通路的抑制活性。
结果如图8和表14A-14B所示，来源于嵌合抗体LT-m37的人源化抗LIGHT抗体(人IgG4形式)均能够对游离LIGHT激活LTβR启动荧光素酶信号进行有效地抑制，且该抑制活性与阳性对照抗体F19相当。
另外，与嵌合抗体LT-m37相比，示例性人源化抗LIGHT抗体hum_LT-m37-13、hum_LT-m37-14、hum_LT-m37-15、hum_LT-m37-16(图8C和表14B)对游离LIGHT激活LTβR启动荧光素酶信号表现出与之相当的抑制活性。
表14A：人源化抗LIGHT抗体抑制游离的LIGHT激活LTβR报告基因的活性
表14B：人源化抗LIGHT抗体抑制游离的LIGHT激活LTβR报告基因的活性
来源于嵌合抗体LT-m58的人源化分子的LTβR抑制活性结果如表14C所示，示例性抗LIGHT抗体hum_LT-m58-1、hum_LT-m58-2能够对游离的LIGHT激活LTβR启动荧光素酶信号进行有效地抑制，且该抑制活性优于阳性对照抗体F19。
表14C：LT-m58的人源化抗LIGHT抗体抑制游离的LIGHT激活LTβR报告基因的活性
来源于嵌合抗体LT-m85的人源化分子的LTβR抑制活性结果如表14D所示，示例性抗LIGHT抗体hum_LT-m85-1、hum_LT-m85-2、hum_LT-m85-3、hum_LT-m85-4能够对游离的LIGHT激活LTβR启动荧光素酶信号进行有效地抑制，且该抑制活性优于阳性对照抗体F19。
表14D：LT-m85的人源化抗LIGHT抗体抑制游离的LIGHT激活LTβR报告基因的活性
人源化抗LIGHT抗体抑制细胞表面LIGHT激活LTβR报告基因的活性检测/
采用实施例2所述的“抗LIGHT抗体抑制人LIGHT激活LTβR报告基因的活性检测”的实验方案，检测人源化后的抗LIGHT抗体对细胞表面LIGHT激活LTβR介导信号通路的抑制活性。
结果如图9和表15A-15B所示，来源于嵌合抗体LT-m37的人源化抗LIGHT抗体(人IgG4形式)均能够对细胞表面LIGHT激活LTβR启动荧光素酶信号进行有效地抑制，且该抑制活性优于阳性对照抗体F19。
另外，与嵌合抗体LT-m37相比，示例性人源化抗LIGHT抗体(人IgG4形式)hum_LT-m37-13、hum_LT-m37-14、hum_LT-m37-15、hum_LT-m37-16(图9C和表15B)对细胞表面LIGHT激活LTβR启动荧光素酶信号表现出与之相当的抑制活性。
表15A：人源化抗LIGHT抗体抑制细胞表面LIGHT激活LTβR报告基因的活性
表15B：人源化抗LIGHT抗体抑制细胞表面LIGHT激活LTβR报告基因的活性

来源于嵌合抗体LT-m58的人源化分子的LTβR抑制活性结果如表15C所示，示例性抗LIGHT抗体hum_LT-m58-1、hum_LT-m58-2能够对细胞表面LIGHT激活LTβR启动荧光素酶信号进行有效地抑制，且该抑制活性优于阳性对照抗体F19。
表15C：LT-m58的人源化抗LIGHT抗体抑制细胞表面LIGHT激活LTβR报告基因的活性
来源于嵌合抗体LT-m85的人源化分子的LTβR抑制活性结果如表15D所示，示例性抗LIGHT抗体hum_LT-m85-1、hum_LT-m85-2、hum_LT-m85-3、hum_LT-m85-4能够对细胞表面LIGHT激活LTβR启动荧光素酶信号进行有效地抑制，且该抑制活性优于阳性对照抗体F19。
表15D：LT-m85的人源化抗LIGHT抗体抑制细胞表面LIGHT激活LTβR报告基因的活性
人源化抗LIGHT抗体抑制游离的LIGHT激活HVEM报告基因的活性检测/
采用实施例2所述的“抗LIGHT抗体抑制人LIGHT激活HVEM报告基因的活性检测”的实验方案，检测人源化后的抗LIGHT抗体对游离的LIGHT激活HVEM介导信号通路的抑制活性。
结果如图10和表16A-16B所示，来源于嵌合抗体LT-m37的示例性人源化抗LIGHT抗体(人IgG4形式)hum_LT-m37-1、hum_LT-m37-2、hum_LT-m37-3、hum_LT-m37-4、hum_LT-m37-5、hum_LT-m37-6(图10A和表16A)、hum_LT-m37-14、hum_LT-m37-15、hum_LT-m37-16(图10B和表16B)能够对游离的LIGHT激活HVEM启动荧光素酶信号进行有效地抑制，且该抑制活性与阳性对照抗体F19相当。
表16A：人源化抗LIGHT抗体抑制游离的LIGHT激活HVEM报告基因的活性

表16B：人源化抗LIGHT抗体抑制游离的LIGHT激活HVEM报告基因的活性
来源于嵌合抗体LT-m58的人源化分子的HVEM抑制活性结果如表16C所示，示例性抗LIGHT抗体hum_LT-m58-1、hum_LT-m58-2能够对游离的LIGHT激活HVEM启动荧光素酶信号进行有效地抑制，且该抑制活性优于阳性对照抗体F19。
表16C：LT-m58的人源化抗LIGHT抗体抑制游离的LIGHT激活HVEM报告基因的活性
来源于嵌合抗体LT-m85的人源化分子的HVEM抑制活性结果如表16D所示，示例性抗LIGHT抗体hum_LT-m85-1、hum_LT-m85-2、hum_LT-m85-3、hum_LT-m85-4能够对游离的LIGHT激活HVEM启动荧光素酶信号进行有效地抑制，且该抑制活性优于阳性对照抗体F19。
表16D：LT-m85的人源化抗LIGHT抗体抑制游离的LIGHT激活HVEM报告基因的活性
人源化抗LIGHT抗体抑制人LIGHT诱导BEAS-2B支气管上皮细胞产生MMP-9的活性检测/
BEAS-2B支气管上皮细胞同时表达LTβR和HVEM受体，LIGHT分别结合受体LTβR或HVEM后，均能诱导支气管上皮细胞分泌蛋白酶MMP-9，从而造成肺组织损伤。通过检测BEAS-2B支气管上皮细胞产生的MMP-9水平，来检测抗LIGHT抗体对游离的LIGHT激活HVEM或LTβR受体的抑制能力，以作为待测抗体抑制LIGHT激活促肺组织重塑机制的衡量指标。
将BEAS-2B支气管上皮细胞(ATCC，CRL-9609)以2×104细胞/孔的密度接种至96孔板，于100μl BMEM全培养基(Lonza，CC-3171，含rhEGF，insulin,triiodothyronine-T3,BPE,transferrin,retinoic acid,epinephrine,hydrocortisone,GA-1000，添加1％PS)、37℃、5％CO2条件下培养过夜。去除上皮细胞培养液，每孔加入50μl浓度为600ng/ml的His-huLIGHT抗原，以及50μl梯度稀释的 待测人源化抗LIGHT抗体(起始浓度为300μg/ml，再作1：3梯度稀释)，其中F19抗体作为阳性对照，补加50μl培养液/孔，轻微震荡混匀后于37℃、5％CO2条件下培养48小时。收集细胞培养液上清，按照制造商的操作说明书，用ELISA试剂盒(博士德，EK0465)检测人MMP-9的水平。简言之，向酶标板加入100μl/孔细胞培养液上清，空白对照孔加入梯度稀释的MMP-9标准样，37℃反应90分钟。用1×洗涤缓冲液洗板后加入100μl/孔MMP-9抗体工作液，37℃反应60分钟。用1×洗涤缓冲液洗板后加入100μl/孔ABC工作液，37℃反应30分钟。用1×洗涤缓冲液洗板后加入90μl/孔TMB显色液，37℃避光反应5-10分钟，立即加入100μl/孔终止液。检测OD 450nm，使用GraphPad Prism 5.0生成MMP-9水平-抗体浓度曲线，计算各抗体抑制人LIGHT诱导BEAS-2B支气管上皮细胞产生MMP-9的IC50值。
结果如图11和表17所示，示例性人源化抗LIGHT抗体(人IgG4形式)hum_LT-m37-13、hum_LT-m37-14、hum_LT-m37-15、hum_LT-m37-16对LIGHT诱导BEAS-2B支气管上皮细胞产生MMP-9的抑制活性优于嵌合抗体LT-m37，或与之相当，且该抑制活性与阳性对照抗体F19相当。
表17：抗LIGHT抗体抑制人LIGHT诱导BEAS-2B支气管上皮细胞产生MMP-9
人源化抗LIGHT抗体抑制人LIGHT刺激CD3+T细胞活化增殖的活性检测/
CD3+T细胞的活化增殖需要共刺激信号。一方面，CD3+T细胞表面的CD3分子受到激动剂刺激；另一方面，CD3+T细胞表达HVEM，LIGHT结合HVEM后，释放共刺激信号，从而共同诱导T细胞的活化增殖。检测人源化抗LIGHT抗体对LIGHT诱导T细胞活化增殖的抑制活性，作为待测人源化抗体抑制LIGHT激活T细胞介导炎症机制的衡量指标。
首先，将浓度为2μg/ml的抗人CD3激动抗体(Biolegend，货号317326)包被至96孔板100μl/孔，4℃孵育过夜。DPBS缓冲液洗板2次后，每孔加入100μl浓度为30μg/ml的His-huLIGHT蛋白，37℃孵育4小时，洗板后去除孔内液体备用。将密度为1.5×106细胞/ml的CD3+T细胞(妙顺/TPCS，PB-N-1C)接种至上述96孔板100μl/孔，加入50μl/孔梯度稀释的待测人源化抗LIGHT抗体(起始浓度为36μg/ml，再作1：3梯度稀释)，其中F19抗体作为阳性对照，无关抗体IgG(来自舒泰神)作为阴性对照(简称NC)，轻微震荡混合后，37℃、5％CO2培养4天。随后用CellTiter-Glo luminescent cell viability assay法(Promega,G7573)检测CD3+T细胞增殖。简言之，加入50μl/孔CellTiter-Glo reagent检测试剂，避光震荡2分钟，静置10分钟，取70μl/孔反应上清转移至白色透明底96孔板。检测Luminescence 1000ms，使用GraphPad Prism 5.0生成Luminescence-抗体浓度曲线，计算各抗体抑制人LIGHT刺激CD3+T细胞增殖的IC50值。
结果如图12和表18所示，示例性人源化抗LIGHT抗体(人IgG4形式)hum_LT-m37-13、hum_LT-m37-14、hum_LT-m37-15、hum_LT-m37-16对LIGHT刺激的CD3+T细胞活化增殖能够进行有效地抑制，且该抑制活性与阳性对照抗体F19相当。
表18：人源化抗LIGHT抗体抑制人LIGHT刺激CD3+T细胞增殖
实施例5：抗LIGHT抗体在LPS诱导的小鼠ARDS模型体内活性验证
LPS诱导的小鼠ARDS模型：脂多糖(LPS)诱导小鼠肺部炎症和免疫系统活化可以导致免疫细胞表面表达LIGHT，也会导致游离LIGHT水平升高，而LIGHT与其受体LTβR或HVEM结合刺激炎性细胞活化，是炎症加剧、推动急性呼吸窘迫综合征(ARDS)进程的重要原因。通过检测抗LIGHT抗体对LPS诱导小鼠ARDS模型体内炎性细胞活化的抑制活性，衡量待测抗体在体内发挥抑制炎症反应的能力。
配置造模剂：取5.5mg LPS(Sigma-Aldrich，L2630-25MG)，充分溶于1.1ml无菌生理盐水中，配置成5mg/ml的LPS溶液，用于气道注射。再从中吸取144μl LPS溶液于8.856ml无菌生理盐水中，配置成0.08mg/ml的LPS溶液，用于腹腔注射。现用现配。
LPS诱导小鼠ARDS模型造模与给药：向7周龄的C57小鼠腹腔注射造模剂LPS 0.8mpk，注射容量为10ml/kg。16小时后通过气道给予造模剂5mg/ml，注射体积为25μl/只。气道给予造模剂后1小时，向实验组小鼠尾静脉注射抗LIGHT抗体，给药剂量为15mpk，其中阴性对照组按照相同的方式注射相同剂量的无关抗体(来自舒泰神)，模型对照组按照相同的方式注射等体积的PBS溶液。给药48小时后处死小鼠，取肺泡灌洗液，分别进行白细胞计数，包括总白细胞、中间细胞、中性粒细胞和淋巴细胞的水平。
结果如图13所示，与模型对照组相比，阴性对照组未显示出显著性差异，但本申请的示例性抗LIGHT抗体LT-m17、hum_LT-m37-12均显著有效地降低了LPS诱导的小鼠ARDS模型肺泡灌洗液中总白细胞(图13A)、中间细胞(图13B)、淋巴细胞(图13C)和中性粒细胞(图13D)的水平。
其他示例性抗LIGHT抗体hum_LT-m37-13、hum_LT-m37-14、hum_LT-m37-15、hum_LT-m37-16(人IgG4形式)、hum_LT-m58-1、hum_LT-m58-2、hum_LT-m58-5、hum_LT-m58-6、hum_LT-m85-1、hum_LT-m85-2、hum_LT-m85-3、hum_LT-m85-4也能够有效地抑制LPS诱导的小鼠ARDS模型肺泡灌洗液中总白细胞、中间细胞、中性粒细胞和淋巴细胞的水平(数据未显示)。

Claims (25)

  1. 一种分离的抗LIGHT抗体，其中所述抗LIGHT抗体包含：
    重链可变结构域(VH)，所述VH包含：
    重链互补决定区(HC-CDR)1，其包含GYFIN(SEQ ID NO:1)；
    HC-CDR2，其包含RIYPYNVNTFYNQNFKG(SEQ ID NO:8)或
    RIYPYNVDTFYNQNFKG(SEQ ID NO:9)；和
    HC-CDR3，其包含GTHYYGSSGAMDY(SEQ ID NO:16)；以及
    轻链可变结构域(VL)，所述VL包含：
    轻链互补决定区(LC-CDR)1，其包含KASQNVGTAVA(SEQ ID NO:23)；
    LC-CDR2，其包含SASNRYT(SEQ ID NO:30)；和
    LC-CDR3，其包含QQYSSYPYT(SEQ ID NO:37)。
  2. 根据权利要求2中所述的分离的抗LIGHT抗体，其包含：
    (i)VH，所述VH包含：HC-CDR1，其包含氨基酸序列SEQ ID NO:1，HC-CDR2，其包含氨基酸序列SEQ ID NO:8，和HC-CDR3，其包含氨基酸序列SEQ ID NO:16；以及VL，所述VL包含：LC-CDR1，其包含氨基酸序列SEQ ID NO:23，LC-CDR2，其包含氨基酸序列SEQ ID NO:30，和LC-CDR3，其包含氨基酸序列SEQ ID NO:37；或
    (ii)VH，所述VH包含：HC-CDR1，其包含氨基酸序列SEQ ID NO:1，HC-CDR2，其包含氨基酸序列SEQ ID NO:9，和HC-CDR3，其包含氨基酸序列SEQ ID NO:16；以及VL，所述VL包含：LC-CDR1，其包含氨基酸序列SEQ ID NO:23，LC-CDR2，其包含氨基酸序列SEQ ID NO:30，和LC-CDR3，其包含氨基酸序列SEQ ID NO:37。
  3. 根据权利要求1-2中任一项所述的分离的抗LIGHT抗体，其包含：
    (i)VH，其包含氨基酸序列SEQ ID NO:46或其变体，所述变体与氨基酸序列SEQ ID NO:46具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:62或其变体，所述变体与氨基酸序列SEQ ID NO:62具有至少约80％序列同一性；
    (ii)VH，其包含氨基酸序列SEQ ID NO:47或其变体，所述变体与氨基酸序列SEQ ID NO:47具有至少约80％序列同一性；以及VL，其包含氨基酸序列 SEQ ID NO:63或其变体，所述变体与氨基酸序列SEQ ID NO:63具有至少约80％序列同一性；
    (iii)VH，其包含氨基酸序列SEQ ID NO:48或其变体，所述变体与氨基酸序列SEQ ID NO:48具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:63或其变体，所述变体与氨基酸序列SEQ ID NO:63具有至少约80％序列同一性；
    (iv)VH，其包含氨基酸序列SEQ ID NO:49或其变体，所述变体与氨基酸序列SEQ ID NO:49具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:63或其变体，所述变体与氨基酸序列SEQ ID NO:63具有至少约80％序列同一性；
    (v)VH，其包含氨基酸序列SEQ ID NO:50或其变体，所述变体与氨基酸序列SEQ ID NO:50具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:63或其变体，所述变体与氨基酸序列SEQ ID NO:63具有至少约80％序列同一性；
    (vi)VH，其包含氨基酸序列SEQ ID NO:47或其变体，所述变体与氨基酸序列SEQ ID NO:47具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:64或其变体，所述变体与氨基酸序列SEQ ID NO:64具有至少约80％序列同一性；
    (vii)VH，其包含氨基酸序列SEQ ID NO:48或其变体，所述变体与氨基酸序列SEQ ID NO:48具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:64或其变体，所述变体与氨基酸序列SEQ ID NO:64具有至少约80％序列同一性；
    (viii)VH，其包含氨基酸序列SEQ ID NO:49或其变体，所述变体与氨基酸序列SEQ ID NO:49具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:64或其变体，所述变体与氨基酸序列SEQ ID NO:64具有至少约80％序列同一性；
    (ix)VH，其包含氨基酸序列SEQ ID NO:50或其变体，所述变体与氨基酸序列SEQ ID NO:50具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:64或其变体，所述变体与氨基酸序列SEQ ID NO:64具有至少约80％序列同一性；
    (x)VH，其包含氨基酸序列SEQ ID NO:47或其变体，所述变体与氨基酸序列SEQ ID NO:47具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:65或其变体，所述变体与氨基酸序列SEQ ID NO:65具有至少约80％序列同一性；
    (xi)VH，其包含氨基酸序列SEQ ID NO:48或其变体，所述变体与氨基酸序列SEQ ID NO:48具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:65或其变体，所述变体与氨基酸序列SEQ ID NO:65具有至少约80％序列同一性；
    (xii)VH，其包含氨基酸序列SEQ ID NO:49或其变体，所述变体与氨基酸序列SEQ ID NO:49具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:65或其变体，所述变体与氨基酸序列SEQ ID NO:65具有至少约80％序列同一性；
    (xiii)VH，其包含氨基酸序列SEQ ID NO:50或其变体，所述变体与氨基酸序列SEQ ID NO:50具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:65或其变体，所述变体与氨基酸序列SEQ ID NO:65具有至少约80％序列同一性；
    (xiv)VH，其包含氨基酸序列SEQ ID NO:51或其变体，所述变体与氨基酸序列SEQ ID NO:51具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:63或其变体，所述变体与氨基酸序列SEQ ID NO:63具有至少约80％序列同一性；
    (xv)VH，其包含氨基酸序列SEQ ID NO:52或其变体，所述变体与氨基酸序列SEQ ID NO:52具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:65或其变体，所述变体与氨基酸序列SEQ ID NO:65具有至少约80％序列同一性；
    (xvi)VH，其包含氨基酸序列SEQ ID NO:53或其变体，所述变体与氨基酸序列SEQ ID NO:53具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:65或其变体，所述变体与氨基酸序列SEQ ID NO:65具有至少约80％序列同一性；或
    (xvii)VH，其包含氨基酸序列SEQ ID NO:51或其变体，所述变体与氨基酸序列SEQ ID NO:51具有至少约80％序列同一性；以及VL，其包含氨基酸序列 SEQ ID NO:65或其变体，所述变体与氨基酸序列SEQ ID NO:65具有至少约80％序列同一性。
  4. 一种分离的抗LIGHT抗体，其包含：
    (i)VH，所述VH包含：HC-CDR1，其包含氨基酸序列SEQ ID NO:2，HC-CDR2，其包含氨基酸序列SEQ ID NO:10，和HC-CDR3，其包含氨基酸序列SEQ ID NO:17；以及VL，所述VL包含：LC-CDR1，其包含氨基酸序列SEQ ID NO:24，LC-CDR2，其包含氨基酸序列SEQ ID NO:31，和LC-CDR3，其包含氨基酸序列SEQ ID NO:38；
    (ii)VH，所述VH包含：HC-CDR1，其包含氨基酸序列SEQ ID NO:2，HC-CDR2，其包含氨基酸序列SEQ ID NO:10，和HC-CDR3，其包含氨基酸序列SEQ ID NO:17；以及VL，所述VL包含：LC-CDR1，其包含氨基酸序列SEQ ID NO:25，LC-CDR2，其包含氨基酸序列SEQ ID NO:31，和LC-CDR3，其包含氨基酸序列SEQ ID NO:39；
    (iii)VH，所述VH包含：HC-CDR1，其包含氨基酸序列SEQ ID NO:3，HC-CDR2，其包含氨基酸序列SEQ ID NO:11，和HC-CDR3，其包含氨基酸序列SEQ ID NO:18；以及VL，所述VL包含：LC-CDR1，其包含氨基酸序列SEQ ID NO:26，LC-CDR2，其包含氨基酸序列SEQ ID NO:32，和LC-CDR3，其包含氨基酸序列SEQ ID NO:40；
    (iv)VH，所述VH包含：HC-CDR1，其包含氨基酸序列SEQ ID NO:3，HC-CDR2，其包含氨基酸序列SEQ ID NO:11，和HC-CDR3，其包含氨基酸序列SEQ ID NO:18；以及VL，所述VL包含：LC-CDR1，其包含氨基酸序列SEQ ID NO:26，LC-CDR2，其包含氨基酸序列SEQ ID NO:32，和LC-CDR3，其包含氨基酸序列SEQ ID NO:41；
    (v)VH，所述VH包含：HC-CDR1，其包含氨基酸序列SEQ ID NO:4，HC-CDR2，其包含氨基酸序列SEQ ID NO:12，和HC-CDR3，其包含氨基酸序列SEQ ID NO:19；以及VL，所述VL包含：LC-CDR1，其包含氨基酸序列SEQ ID NO:27，LC-CDR2，其包含氨基酸序列SEQ ID NO:33，和LC-CDR3，其包含氨基酸序列SEQ ID NO:42；或
    (vi)VH，所述VH包含：HC-CDR1，其包含氨基酸序列SEQ ID NO:5，HC-CDR2，其包含氨基酸序列SEQ ID NO:13，和HC-CDR3，其包含氨基酸序 列SEQ ID NO:20；以及VL，所述VL包含：LC-CDR1，其包含氨基酸序列SEQ ID NO:28，LC-CDR2，其包含氨基酸序列SEQ ID NO:34，和LC-CDR3，其包含氨基酸序列SEQ ID NO:43。
  5. 根据权利要求4中所述的分离的抗LIGHT抗体，其包含：
    (i)VH，其包含SEQ ID NO:54所示的氨基酸序列或其变体，所述变体与SEQ ID NO:54所示的氨基酸序列具有至少约80％序列同一性；以及VL，其包含SEQ ID NO:66所示的氨基酸序列或其变体，所述变体与SEQ ID NO:66所示的氨基酸序列具有至少约80％序列同一性；
    (ii)VH，其包含SEQ ID NO:55所示的氨基酸序列或其变体，所述变体与SEQ ID NO:55所示的氨基酸序列具有至少约80％序列同一性；以及VL，其包含SEQ ID NO:67所示的氨基酸序列或其变体，所述变体与SEQ ID NO:67所示的氨基酸序列具有至少约80％序列同一性；
    (iii)VH，其包含SEQ ID NO:56所示的氨基酸序列或其变体，所述变体与SEQ ID NO:56所示的氨基酸序列具有至少约80％序列同一性；以及VL，其包含SEQ ID NO:68所示的氨基酸序列或其变体，所述变体与SEQ ID NO:68所示的氨基酸序列具有至少约80％序列同一性；
    (iv)VH，其包含SEQ ID NO:57所示的氨基酸序列或其变体，所述变体与SEQ ID NO:57所示的氨基酸序列具有至少约80％序列同一性；以及VL，其包含SEQ ID NO:69所示的氨基酸序列或其变体，所述变体与SEQ ID NO:69所示的氨基酸序列具有至少约80％序列同一性；
    (v)VH，其包含SEQ ID NO:58所示的氨基酸序列或其变体，所述变体与SEQ ID NO:58所示的氨基酸序列具有至少约80％序列同一性；以及VL，其包含SEQ ID NO:70所示的氨基酸序列或其变体，所述变体与SEQ ID NO:70所示的氨基酸序列具有至少约80％序列同一性；或
    (vi)VH，其包含SEQ ID NO:59所示的氨基酸序列或其变体，所述变体与SEQ ID NO:59所示的氨基酸序列具有至少约80％序列同一性；以及VL，其包含SEQ ID NO:71所示的氨基酸序列或其变体，所述变体与SEQ ID NO:71所示的氨基酸序列具有至少约80％序列同一性。
  6. 一种分离的抗LIGHT抗体，其中所述抗LIGHT抗体包含：
    重链可变结构域(VH)，所述VH包含：
    重链互补决定区(HC-CDR)1，其包含DHIMN(SEQ ID NO:6)；
    HC-CDR2，其包含RIYPVSGETNYNQKFMG(SEQ ID NO:14)；和
    HC-CDR3，其包含GSYYWNAMDY(SEQ ID NO:21)；以及
    轻链可变结构域(VL)，所述VL包含：
    轻链互补决定区(LC-CDR)1，其包含KASQSVDFDGDSYMN(SEQ ID NO:29)或KASQSVDFDGESYMN(SEQ ID NO:83)；
    LC-CDR2，其包含SASNLES(SEQ ID NO:35)；和
    LC-CDR3，其包含QQSIEDPWT(SEQ ID NO:43)。
  7. 根据权利要求6中所述的分离的抗LIGHT抗体，其包含：
    (i)VH，所述VH包含：HC-CDR1，其包含氨基酸序列SEQ ID NO:6，HC-CDR2，其包含氨基酸序列SEQ ID NO:14，和HC-CDR3，其包含氨基酸序列SEQ ID NO:21；以及VL，所述VL包含：LC-CDR1，其包含氨基酸序列SEQ ID NO:29，LC-CDR2，其包含氨基酸序列SEQ ID NO:35，和LC-CDR3，其包含氨基酸序列SEQ ID NO:43；或
    (ii)VH，所述VH包含：HC-CDR1，其包含氨基酸序列SEQ ID NO:6，HC-CDR2，其包含氨基酸序列SEQ ID NO:14，和HC-CDR3，其包含氨基酸序列SEQ ID NO:21；以及VL，所述VL包含：LC-CDR1，其包含氨基酸序列SEQ ID NO:83，LC-CDR2，其包含氨基酸序列SEQ ID NO:35，和LC-CDR3，其包含氨基酸序列SEQ ID NO:43。
  8. 根据权利要求6-7中任一项所述的分离的抗LIGHT抗体，其包含：
    (i)VH，其包含氨基酸序列SEQ ID NO:60或其变体，所述变体与氨基酸序列SEQ ID NO:60具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:72或其变体，所述变体与氨基酸序列SEQ ID NO:72具有至少约80％序列同一性；
    (ii)VH，其包含氨基酸序列SEQ ID NO:84或其变体，所述变体与氨基酸序列SEQ ID NO:84具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:86或其变体，所述变体与氨基酸序列SEQ ID NO:86具有至少约80％序列同一性；
    (iii)VH，其包含氨基酸序列SEQ ID NO:85或其变体，所述变体与氨基酸序列SEQ ID NO:85具有至少约80％序列同一性；以及VL，其包含氨基酸序列 SEQ ID NO:87或其变体，所述变体与氨基酸序列SEQ ID NO:87具有至少约80％序列同一性；
    (iv)VH，其包含氨基酸序列SEQ ID NO:84或其变体，所述变体与氨基酸序列SEQ ID NO:84具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:88或其变体，所述变体与氨基酸序列SEQ ID NO:88具有至少约80％序列同一性；
    (v)VH，其包含氨基酸序列SEQ ID NO:84或其变体，所述变体与氨基酸序列SEQ ID NO:84具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:89或其变体，所述变体与氨基酸序列SEQ ID NO:89具有至少约80％序列同一性；
    (vi)VH，其包含氨基酸序列SEQ ID NO:85或其变体，所述变体与氨基酸序列SEQ ID NO:85具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:90或其变体，所述变体与氨基酸序列SEQ ID NO:90具有至少约80％序列同一性；或
    (vii)VH，其包含氨基酸序列SEQ ID NO:84或其变体，所述变体与氨基酸序列SEQ ID NO:84具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:91或其变体，所述变体与氨基酸序列SEQ ID NO:91具有至少约80％序列同一性。
  9. 一种分离的抗LIGHT抗体，其中所述抗LIGHT抗体包含：
    重链可变结构域(VH)，所述VH包含：
    重链互补决定区(HC-CDR)1，其包含SYNVH(SEQ ID NO:7)；
    HC-CDR2，其包含AVYPGNGDTSYNQKFKG(SEQ ID NO:15)；和
    HC-CDR3，其包含GSYYYTSSYFDH(SEQ ID NO:22)；以及
    轻链可变结构域(VL)，所述VL包含：
    轻链互补决定区(LC-CDR)1，其包含KASQSVDFDGDSYMN(SEQ ID NO:29)；
    LC-CDR2，其包含TASNLES(SEQ ID NO:36)；和
    LC-CDR3，其包含QQSYEDPFT(SEQ ID NO:44)。
  10. 根据权利要求9中所述的分离的抗LIGHT抗体，其包含：
    (i)VH，其包含氨基酸序列SEQ ID NO:61或其变体，所述变体与氨基酸序列SEQ ID NO:61具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:73或其变体，所述变体与氨基酸序列SEQ ID NO:73具有至少约80％序列同一性；
    (ii)VH，其包含氨基酸序列SEQ ID NO:92或其变体，所述变体与氨基酸序列SEQ ID NO:92具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:95或其变体，所述变体与氨基酸序列SEQ ID NO:95具有至少约80％序列同一性；
    (iii)VH，其包含氨基酸序列SEQ ID NO:93或其变体，所述变体与氨基酸序列SEQ ID NO:93具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:96或其变体，所述变体与氨基酸序列SEQ ID NO:96具有至少约80％序列同一性；
    (iv)VH，其包含氨基酸序列SEQ ID NO:92或其变体，所述变体与氨基酸序列SEQ ID NO:92具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:96或其变体，所述变体与氨基酸序列SEQ ID NO:96具有至少约80％序列同一性；
    (v)VH，其包含氨基酸序列SEQ ID NO:94或其变体，所述变体与氨基酸序列SEQ ID NO:94具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:97或其变体，所述变体与氨基酸序列SEQ ID NO:97具有至少约80％序列同一性；
    (vi)VH，其包含氨基酸序列SEQ ID NO:94或其变体，所述变体与氨基酸序列SEQ ID NO:94具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:98或其变体，所述变体与氨基酸序列SEQ ID NO:98具有至少约80％序列同一性；
    (vii)VH，其包含氨基酸序列SEQ ID NO:93或其变体，所述变体与氨基酸序列SEQ ID NO:93具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:98或其变体，所述变体与氨基酸序列SEQ ID NO:98具有至少约80％序列同一性；
    (viii)VH，其包含氨基酸序列SEQ ID NO:92或其变体，所述变体与氨基酸序列SEQ ID NO:92具有至少约80％序列同一性；以及VL，其包含氨基酸序列 SEQ ID NO:98或其变体，所述变体与氨基酸序列SEQ ID NO:98具有至少约80％序列同一性；
    (ix)VH，其包含氨基酸序列SEQ ID NO:94或其变体，所述变体与氨基酸序列SEQ ID NO:94具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:99或其变体，所述变体与氨基酸序列SEQ ID NO:99具有至少约80％序列同一性；或
    (x)VH，其包含氨基酸序列SEQ ID NO:92或其变体，所述变体与氨基酸序列SEQ ID NO:92具有至少约80％序列同一性；以及VL，其包含氨基酸序列SEQ ID NO:99或其变体，所述变体与氨基酸序列SEQ ID NO:99具有至少约80％序列同一性。
  11. 根据权利要求1-10中任一项所述的分离的抗LIGHT抗体，其中所述抗LIGHT抗体与人LIGHT结合的Kd值为约0.1pM至约10nM。
  12. 根据权利要求1-11中任一项的分离的抗LIGHT抗体，其中所述抗LIGHT抗体包含Fc片段。
  13. 根据权利要求12中的分离的抗LIGHT抗体，其中所述抗LIGHT抗体是全长的IgA、IgD、IgE、IgG或IgM抗体。
  14. 根据权利要求13中的分离的抗LIGHT抗体，其中所述抗LIGHT抗体是全长的IgG1、IgG2、IgG3或IgG4抗体。
  15. 根据权利要求1-14中任一项的分离的抗LIGHT抗体，其中所述抗LIGHT抗体是嵌合的、人的或人源化的抗体。
  16. 根据权利要求1-11中任一项的分离的抗LIGHT抗体，其中所述抗LIGHT抗体是抗原结合片段，所述抗原结合片段选自Fab、Fab’、F(ab)’2、Fab’-SH、单链Fv(scFv)、Fv片段、dAb、Fd、纳米抗体(nanobody)、双链抗体(diabody)和线性抗体。
  17. 一种分离的编码权利要求1-16中任一项所述的抗LIGHT抗体的核酸分子。
  18. 一种包含权利要求17中所述的核酸分子的载体。
  19. 一种分离的宿主细胞，其包含权利要求1-16中任一项所述的抗LIGHT抗体、权利要求17中所述的核酸分子或权利要求18中所述的载体。
  20. 一种制备抗LIGHT抗体的方法，其包含：
    a)在能有效表达抗LIGHT抗体的条件下培养权利要求19中所述的宿主细胞；和
    b)从宿主细胞中获得表达的抗LIGHT抗体。
  21. 一种药物组合物，其包含权利要求1-16中任一项所述的抗LIGHT抗体、权利要求17中所述的核酸分子、权利要求18中所述的载体、权利要求19中所述的分离的宿主细胞或由权利要求20中所述方法制备得到的抗体，以及药学上可接受的载体。
  22. 一种治疗所需个体疾病或病症的方法，包括向所述个体施用有效量的权利要求1-16中任一项所述的抗体、权利要求17中所述的核酸分子、权利要求18中所述的载体、权利要求19中所述的宿主细胞、由权利要求20中所述方法制备得到的抗体、或权利要求21中所述的药物组合物。
  23. 权利要求1-16中任一项所述的抗体、权利要求17中所述的核酸分子、权利要求18中所述的载体、权利要求19中所述的宿主细胞、由权利要求20中所述方法制备得到的抗体、或权利要求21中所述的药物组合物在制备治疗有此需求的个体疾病或病症的药物中的用途。
  24. 根据权利要求22中的方法或权利要求23中的用途，其中所述疾病或病症是LIGHT信号通路失调导致的疾病和/或病症，例如自身免疫性疾病和/或炎症疾病。
  25. 根据权利要求22中的方法或权利要求23中的用途，其中所述疾病或病症选自炎性肠道疾病(IBD)、克罗恩疾病、溃疡性结肠炎、强直性脊柱炎、异位性皮炎、类风湿性关节炎、细支气管炎、移植排斥反应、同种移植排斥反应、移植物抗宿主病(GVHD)、哮喘、嗜酸性食管炎、急性呼吸窘迫综合征(ARDS)、慢性心脏衰竭、慢性阻塞性肺病(COPD)、败血性休克、纤维化疾病、皮肤纤维化、特发性肺纤维化、肾纤维化、慢性肾病、系统性硬化、多发性硬化症、斯耶格伦氏综合征、狼疮、气道炎症、银屑病、肝炎、乳糜泻、原发性胆汁肝硬化、自身免疫性溶血性贫血、自身免疫性新生儿血小板减少症、原发性血小板减少性紫癜、非酒精性脂肪肝、COVID19。
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