WO2025006549A2 - Antibodies against immune checkpoint molecules and methods of use - Google Patents

Antibodies against immune checkpoint molecules and methods of use Download PDF

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WO2025006549A2
WO2025006549A2 PCT/US2024/035540 US2024035540W WO2025006549A2 WO 2025006549 A2 WO2025006549 A2 WO 2025006549A2 US 2024035540 W US2024035540 W US 2024035540W WO 2025006549 A2 WO2025006549 A2 WO 2025006549A2
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amino acid
acid sequence
seq
antibody
cdr3
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WO2025006549A3 (en
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Laijun Lai
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University of Connecticut
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2803—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2803—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
    • C07K16/2827—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against B7 molecules, e.g. CD80, CD86
    • 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
    • A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding

Definitions

  • T lymphocytes are the major component in the immune system. Many cancers protect themselves from the immune system attack by producing immune checkpoint molecules to inhibit the functions of T cells and/or other immune cells.
  • immune checkpoint molecules such as PD-L1/PD-1, CTLA-4 and LAG3 have been approved by the FDA for the ⁇ treatment of cancer and autoimmune disease.
  • targeting the existing immune checkpoint molecules has achieved some success, a complete and durable response was only seen in a fraction of treated patients. The results suggest that the immune system is regulated by additional checkpoint molecules.
  • the disclosure provides isolated anti-human BTN5 (ERMAP) antibodies, or fragments thereof, comprising 1, 2, 3, 4, 5, or all 6 complementarity determining regions (CDRs) selected from the group consisting of: 1 ⁇ ⁇ Heavy chain CDR1 (H-CDR1) comprising an amino acid sequence at least 80%, 85%, 90%, 95%, or 100% identical to the amino acid sequenceSYYIH (SEQ ID NO: 1); Heavy chain CDR2 (H-CDR2) comprising an amino acid sequence at least 80%, 85%, 90%, 95%, or 100% identical to the amino acid sequenceWIYPGNVNTKYNEKFKG ⁇ (SEQ ID NO: 2); Heavy chain CDR3 (H-CDR3) comprising an amino acid sequence at least 80%, 85%, 90%, 95%, or 100% identical to the amino acid sequenceGDYDGGYAMDY (SEQ ID NO: 3).
  • H-CDR1 Heavy chain CDR1
  • H-CDR2 Heavy chain CDR2
  • H-CDR3 Heavy chain CDR3 (H
  • Light chain CDR1 comprising an amino acid sequence at least 80%, 85%, ⁇ 90%, 95%, or 100% identical to the amino acid sequenceRSSKSLLHSNGNTYLY (SEQ ID NO: 4);
  • Light chain CDR2 comprising an amino acid sequence at least 80%, 85%, 90%, 95%, or 100% identical to the amino acid sequenceRMSNLAS (SEQ ID NO: 5);
  • Light chain CDR3 comprising an amino acid sequence at least 80%, 85%, ⁇ 90%, 95%, or 100% identical to the amino acid sequenceMQHLEYPLT (SEQ ID NO: 6).
  • chemotherapeutic agents include alkylating agents such as thiotepa and cyclosphosphamide; alkyl sulfonates such as busulfan, improsulfan and 23 ⁇ ⁇ piposulfan; aziridines such as benzodopa, carboquone, meturedopa, and uredopa; ethylenimines and methylamelamines including altretamine, triethylenemelamine, triethylenephosphoramide, triethylenethiophosphoramide and trimethylolomelamine; acetogenins (especially bullatacin and bullatacinone); a camptothecin (including the synthetic ⁇ analogue topotecan); bryostatin; callystatin; CC-1065 (including its adozelesin, carzelesin and bizelesin synthetic analogues); cryptophycins (particularly cryptophycin 1 and cryptophycin 8); dolastatin; duocarmycin (including the
  • calicheamicin especially calicheamicin gamma 11 and calicheamicin omega 11 (see, e.g., Agnew, Chem Intl. Ed. Engl., 33: 183-186 (1994)); ⁇ dynemicin, including dynemicin A; bisphosphonates, such as clodronate; an esperamicin; as well as neocarzinostatin chromophore and related chromoprotein enediyne antibiotic chromophores), aclacinomysins, actinomycin, authramycin, azaserine, bleomycins, cactinomycin, carabicin, carminomycin, carzinophilin, chromomycinis, dactinomycin, daunorubicin, detorubicin, 6-diazo-5-oxo-L-norleucine, doxorubicin (including morpholino- ⁇ doxor
  • the antibodies or fragments thereof are linked to a detectable label, such as a radiolabel, an enzyme, a fluorescent label, a luminescent label, a bioluminescent label, a magnetic label, and/or biotin.
  • a detectable label such as a radiolabel, an enzyme, a fluorescent label, a luminescent label, a bioluminescent label, a magnetic label, and/or biotin.
  • the agent and/or detectable label is conjugated directly to the antibodies or fragments thereof.
  • the agent and/or detectable label is ⁇ conjugated to the antibodies or fragments thereof via a linker.
  • the present disclosure provides nucleic acids encoding the antibodies or fragments thereof of any aspect or embodiment of the invention.
  • the nucleic acid sequence may comprise RNA or DNA.
  • Recombinant expression vector includes vectors that operatively link a nucleic acid coding region or gene to any control sequences capable of effecting ⁇ expression of the gene product.
  • Control sequences operably linked to the nucleic acid sequences of the disclosure are nucleic acid sequences capable of effecting the expression of the nucleic acid molecules. The control sequences need not be contiguous with the nucleic acid sequences, so long as they function to direct the expression thereof. Thus, for example, intervening untranslated yet transcribed sequences can be present between a promoter ⁇ sequence and the nucleic acid sequences and the promoter sequence can still be considered “operably linked" to the coding sequence.
  • control sequences include, but are not limited to, polyadenylation signals, termination signals, and ribosome binding sites.
  • expression vectors can be of any type known in the art, including but not limited plasmid and viral-based expression vectors.
  • the control sequence used to drive expression of the ⁇ disclosed nucleic acid sequences in a mammalian system may be constitutive (driven by any of a variety of promoters, including but not limited to, CMV, SV40, RSV, actin, EF) or inducible (driven by any of a number of inducible promoters including, but not limited to, tetracycline, ecdysone, steroid-responsive.
  • the pharmaceutical composition includes a bulking agent, like glycine.
  • the pharmaceutical composition includes a surfactant e.g., polysorbate-20, polysorbate-40, polysorbate- 60, polysorbate-65, polysorbate-80 polysorbate-85, poloxamer-188, sorbitan monolaurate, sorbitan monopalmitate, sorbitan monostearate, sorbitan monooleate, sorbitan trilaurate, sorbitan tristearate, sorbitan trioleaste, or a combination thereof.
  • the pharmaceutical composition may also include a tonicity adjusting agent, e.g., a compound ⁇ that renders the formulation substantially isotonic or isoosmotic with human blood.
  • a suitable dosage range may, for instance, be 0.1 ug/kg-100 mg/kg body weight; alternatively, it may be 0.5 ug/kg to 50 mg/kg; 1 ug/kg to 25 mg/kg, or 5 ug/kg to 10 mg/kg body weight.
  • the therapeutic can be delivered in a single bolus, or may be administered more than once (e.g., 2, 3, 4, 5, or more times) as determined ⁇ by attending medical personnel.
  • the phrase “amount effective” or “the like refers to an amount that provides a therapeutic benefit in the treatment, of cancer or autoimmune disease. Determination of a therapeutically effective amount is well within the capability of those skilled in the art.
  • a therapeutically effective amount can vary with the subject's ⁇ history, age, condition, sex, as well as the severity and type of the medical condition in the subject, and administration of other pharmaceutically active agents.
  • Murine monoclonal antibodies (mAbs) of the disclosure were generated against human ERMAP, TAPBPL and CD300c, and shown to enhance antitumor immunity and inhibit tumor growth in animal models ( Figures 10-14).
  • the hybridomas that produce the murine mAbs were sequenced, and chimeric Abs in which the murine variable domains of ⁇ each mAb are linked to human constant regions were generated (SEQ ID NO:50-65).
  • the anti-ERMAP chimeric Ab (SEQ ID NO:50-51) was demonstrated to neutralize the inhibitory activity of ERMAP-Ig on T cell activation (reduced CD69 expression on CD4 and CD8 T cells) ( Figure 1).
  • T cells were stimulated with anti-CD3 antibody in the presence of 8 ⁇ g/ml hERMAP protein and 25 ⁇ ⁇ g/ml anti-hERMAP chimeric antibody or control IgG.
  • Flow cytometry analysis quantification ( Figure 1A) demonstrated reduced CD69 expression on CD4 + T cells.
  • Flow cytometry analysis quantification (Figure 1B) demonstrated reduced CD69 expression on CD8 + T cells.
  • CD4 + T cells and CD8 + T cells infiltrate tumors to mediate an antitumor immune ⁇ response (Tay et al. Cancer Gene Ther 28: 5-17 (2021)).
  • Anti-TAPBPL chimeric Ab SEQ ID NO: 62-63 treatment increased tumor infiltrating CD4 + T cells and CD8 + T cells (Figure 9).
  • BALB/c mice were injected subcutaneously (s.c.) with CT 26 colon cancer cells on day 0, followed by injection of the anti-TAPBPL chimeric Ab (100 ⁇ g) or control (isotype) Ab (100 ⁇ g) on days 3, 5, 7, 9, and 12. The colon cancers were harvested on day 30.
  • FIG. 2B Treatment with anti-hERMAP inhibited tumor growth compared with control starting at day 9 and through day 15. Survival of leukemia-bearing mice treated with anti-hERMAP was compared with control ( Figure 3). DBA/2J mice were injected with 2 ⁇ 10 5 P388 murine leukemia cells on day 0, followed by injection of the anti- hERMAP mAb (100 ⁇ g) or control (isotype) Ab (100 ⁇ ⁇ g) on days 3, 5, 7, 9, and 12. The graph shows a Kaplan-Meier curve for the survival of control treated versus anti-hERMAP treated leukemia-bearing mice. The survival of the mice was monitored over time.
  • Antibodies against TAPBPL inhibits tumor growth and promotes tumor infiltration. The impact of anti-TAPBPL on malignancy growth/progression was also assessed.
  • Anti-TAPBPL chimeric Ab (SEQ ID NO:62-63) inhibited tumor growth in melanoma ( Figure 6A) and colon cancer animal models ( Figure 6B).
  • C57BL/6 or BALB/c mice were ⁇ injected subcutaneously (s.c.) with B16F10 melanoma cells or CT 26 colon cancer cells on day 0, followed by injection of the anti-TAPBPL chimeric Ab (100 ⁇ g) or control (isotype) Ab (100 ⁇ g) on days 3, 5, 7, 9, and 12.
  • the melanomas and colon cancers were harvested on day 20 and 30, respectively.
  • Anti-hTAPBPL increased both CD4 + T cells (Figure 7B) and CD8 + T cells (Figure 7C) in the tumors, which are involved in tumor infiltration, compared with control. 31 ⁇ ⁇ Anti-hTAPBPL was then tested in an established cancer leukemia model ( Figure 8). Syngeneic DBA/2J mice were injected subcutaneously (s.c.) with P388 leukemia cells. When cancers were visible and palpable, the mice were injected s.c. with graded doses of anti- hTAPBPL Ab (50, 100, and 200 ⁇ g) or control Ab. The data demonstrated that anti- ⁇ hTAPBPL treats established cancer in a leukemia model as shown by the slowing in growth of tumor volume over time. 32 ⁇ ⁇

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Abstract

Antibodies against the immune checkpoint molecules Erythroid membrane-associated protein (ERMAP/BTN5), TAP Binding Protein Like protein (TAPBPL), and CD300c are provided, and their use for treating cancer.

Description

UCONN 23-074 Antibodies against immune checkpoint molecules and methods of use ^ Statement of Government Support This invention was made with government support under AG072234, AI175087, and AI123131 awarded by the National Institutes of Health. The government has certain rights in the invention. ^ Sequence Listing Statement A computer readable form of the Sequence Listing is filed with this application by electronic submission and is incorporated into this application by reference in its entirety. The Sequence Listing is contained in the file created on June 11, 2024 having the file name “23-^ 0840-WO.xml” and is 70,186 bytes in size.^ Background Tumor progression is often accompanied by profound immune suppression that interferes with an effective antitumor response and tumor elimination. Immune cells are^ regulated by checkpoint molecules. T lymphocytes (T cells) are the major component in the immune system. Many cancers protect themselves from the immune system attack by producing immune checkpoint molecules to inhibit the functions of T cells and/or other immune cells. In the past several years, several new drugs that target immune checkpoint molecules such as PD-L1/PD-1, CTLA-4 and LAG3 have been approved by the FDA for the^ treatment of cancer and autoimmune disease. Although targeting the existing immune checkpoint molecules has achieved some success, a complete and durable response was only seen in a fraction of treated patients. The results suggest that the immune system is regulated by additional checkpoint molecules. ^ Summary In one aspect, the disclosure provides isolated anti-human BTN5 (ERMAP) antibodies, or fragments thereof, comprising 1, 2, 3, 4, 5, or all 6 complementarity determining regions (CDRs) selected from the group consisting of: 1^ ^ Heavy chain CDR1 (H-CDR1) comprising an amino acid sequence at least 80%, 85%, 90%, 95%, or 100% identical to the amino acid sequenceSYYIH (SEQ ID NO: 1); Heavy chain CDR2 (H-CDR2) comprising an amino acid sequence at least 80%, 85%, 90%, 95%, or 100% identical to the amino acid sequenceWIYPGNVNTKYNEKFKG^ (SEQ ID NO: 2); Heavy chain CDR3 (H-CDR3) comprising an amino acid sequence at least 80%, 85%, 90%, 95%, or 100% identical to the amino acid sequenceGDYDGGYAMDY (SEQ ID NO: 3). Light chain CDR1 (L-CDR1) comprising an amino acid sequence at least 80%, 85%,^ 90%, 95%, or 100% identical to the amino acid sequenceRSSKSLLHSNGNTYLY (SEQ ID NO: 4); Light chain CDR2 (L-CDR2) comprising an amino acid sequence at least 80%, 85%, 90%, 95%, or 100% identical to the amino acid sequenceRMSNLAS (SEQ ID NO: 5); and Light chain CDR3 (L-CDR3) comprising an amino acid sequence at least 80%, 85%,^ 90%, 95%, or 100% identical to the amino acid sequenceMQHLEYPLT (SEQ ID NO: 6). In one embodiment, the anti-human BTN5 (ERMAP) antibody, or fragment thereof, comprises: an H-CDR1 comprising the amino acid sequence of SEQ ID NO:1; an H-CDR2 comprising the amino acid sequence of SEQ ID NO:2; ^ an H-CDR3 comprising the amino acid sequence of SEQ ID NO:3; an L-CDR1 comprising the amino acid sequence of SEQ ID NO:4; an L-CDR2 comprising the amino acid sequence of SEQ ID NO:5; and an L-CDR3 comprising the amino acid sequence of SEQ ID NO:6. In another aspect, the disclosure provides isolated anti-human TAPBPL antibodies, or^ fragments thereof, comprising 1, 2, 3, 4, 5, or all 6 complementarity determining regions (CDRs) selected from the group consisting of: Heavy chain CDR1 (H-CDR1) comprising an amino acid sequence at least 80%, 85%, 90%, 95%, or 100% identical to the amino acid sequenceNYWIE (SEQ ID NO:9); Heavy chain CDR2 (H-CDR2) comprising an amino acid sequence at least 80%,^ 85%, 90%, 95%, or 100% identical to the amino acid sequenceEILPGSGSTNYNEKFKG (SEQ ID NO:10); 2^ ^ Heavy chain CDR3 (H-CDR3) comprising an amino acid sequence at least 80%, 85%, 90%, 95%, or 100% identical to the amino acid sequenceFTMARYWYFDV (SEQ ID NO:11); Light chain CDR1 (L-CDR1) comprising an amino acid sequence at least 80%, 85%,^ 90%, 95%, or 100% identical to the amino acid sequenceRSSTGAVTTSNYAN (SEQ ID NO:12); Light chain CDR2 (L-CDR2) comprising an amino acid sequence at least 80%, 85%, 90%, 95%, or 100% identical to the amino acid sequenceGTSNRAP (SEQ ID NO:13); and Light chain CDR3 (L-CDR3) comprising an amino acid sequence at least 80%, 85%,^ 90%, 95%, or 100% identical to the amino acid sequenceALWYSTH(F/Y)V (SEQ ID NO:14),; wherein residues in parentheses are options at that position. In one embodiment, the anti-human TAPBPL antibodies, or fragments thereof, comprise: ^ an H-CDR1 comprising the amino acid sequence of SEQ ID NO:9; an H-CDR2 comprising the amino acid sequence of SEQ ID NO:10; an H-CDR3 comprising the amino acid sequence of SEQ ID NO:11; an L-CDR1 comprising the amino acid sequence of SEQ ID NO:12; an L-CDR2 comprising the amino acid sequence of SEQ ID NO:13; and^ an L-CDR3 comprising the amino acid sequence of SEQ ID NO:14. In a further aspect, the disclosure provides isolated anti-human TAPBPL antibodies, or fragments thereof, comprising 1, 2, 3, 4, 5, or all 6 complementarity determining regions (CDRs) selected from the group consisting of: Heavy chain CDR1 (H-CDR1) comprising an amino acid sequence at least 80%,^ 85%, 90%, 95%, or 100% identical to the amino acid sequenceRYWMS (SEQ ID NO:18); Heavy chain CDR2 (H-CDR2) comprising an amino acid sequence at least 80%, 85%, 90%, 95%, or 100% identical to the amino acid sequenceEINPDSSTINYTPSLKD (SEQ ID NO:19); Heavy chain CDR3 (H-CDR3) comprising an amino acid sequence at least 80%,^ 85%, 90%, 95%, or 100% identical to the amino acid sequenceVTTVVARDWYFDV (SEQ ID NO:20); Light chain CDR1 (L-CDR1) comprising an amino acid sequence at least 80%, 85%, 90%, 95%, or 100% identical to the amino acid sequence of SEQ ID NO:12; 3^ ^ Light chain CDR2 (L-CDR2) comprising an amino acid sequence at least 80%, 85%, 90%, 95%, or 100% identical to the amino acid sequence of SEQ ID NO:13; and Light chain CDR3 (L-CDR3) comprising an amino acid sequence at least 80%, 85%, 90%, 95%, or 100% identical to the amino acid sequence of SEQ ID NO:14. ^ In one embodiment, the anti-human TAPBPL antibodies, or fragments thereof, comprise: an H-CDR1 comprising the amino acid sequence of SEQ ID NO:18; an H-CDR2 comprising the amino acid sequence of SEQ ID NO:19; an H-CDR3 comprising the amino acid sequence of SEQ ID NO:20; ^ an L-CDR1 comprising the amino acid sequence of SEQ ID NO:12; an L-CDR2 comprising the amino acid sequence of SEQ ID NO:13; and an L-CDR3 comprising the amino acid sequence of SEQ ID NO:14. In one aspect, the disclosure provides isolated anti-human CD300c antibodies, or fragments thereof, comprising 1, 2, 3, 4, 5, or all 6 complementarity determining regions^ (CDs) selected from the group consisting of: Heavy chain CDR1 (H-CDR1) comprising an amino acid sequence at least 80%, 85%, 90%, 95%, or 100% identical to the amino acid sequenceGYNMN (SEQ ID NO:23); Heavy chain CDR2 (H-CDR2) comprising an amino acid sequence at least 80%, 85%, 90%, 95%, or 100% identical to the amino acid sequenceNIDPYYGGTSYNQKFKG^ (SEQ ID NO:24); Heavy chain CDR3 (H-CDR3) comprising an amino acid sequence at least 80%, 85%, 90%, 95%, or 100% identical to the amino acid sequenceSGYYYAMDY (SEQ ID NO:25); Light chain CDR1 (L-CDR1) comprising an amino acid sequence at least 80%, 85%,^ 90%, 95%, or 100% identical to the amino acid sequenceKASQNVGTAVA (SEQ ID NO:26); Light chain CDR2 (L-CDR2) comprising an amino acid sequence at least 80%, 85%, 90%, 95%, or 100% identical to the amino acid sequenceSASNRYT (SEQ ID NO:27); and Light chain CDR3 (L-CDR3) comprising an amino acid sequence at least 80%, 85%, 90%, 95%, or 100% identical to the amino acid sequenceQQYSSYPYT (SEQ ID NO:28).^ In one embodiment, the anti-human CD300c antibodies, or fragments thereof, comprise: an H-CDR1 comprising the amino acid sequence of SEQ ID NO:23; an H-CDR2 comprising the amino acid sequence of SEQ ID NO:24; 4^ ^ an H-CDR3 comprising the amino acid sequence of SEQ ID NO:25; an L-CDR1 comprising the amino acid sequence of SEQ ID NO:26; an L-CDR2 comprising the amino acid sequence of SEQ ID NO:27; and an L-CDR3 comprising the amino acid sequence of SEQ ID NO:28. ^ The disclosure also provides isolated anti-human CD300c antibodies, or fragments thereof, comprising 1, 2, 3, 4, 5, or all 6 complementarity determining regions (CDs) selected from the group consisting of: Heavy chain CDR1 (H-CDR1) comprising an amino acid sequence at least 80%, 85%, 90%, 95%, or 100% identical to the amino acid sequenceDYYMK (SEQ ID NO:31);^ Heavy chain CDR2 (H-CDR2) comprising an amino acid sequence at least 80%, 85%, 90%, 95%, or 100% identical to the amino acid sequence DINPNNGDTFYNQKFKG (SEQ ID NO:32); Heavy chain CDR3 (H-CDR3) comprising an amino acid sequence at least 80%, 85%, 90%, 95%, or 100% identical to the amino acid sequenceGGMVTTAMDY (SEQ ID^ NO:33); Light chain CDR1 (L-CDR1) comprising an amino acid sequence at least 80%, 85%, 90%, 95%, or 100% identical to the amino acid sequenceRTITDIDDDMN (SEQ ID NO:34); Light chain CDR2 (L-CDR2) comprising an amino acid sequence at least 80%, 85%, 90%, 95%, or 100% identical to the amino acid sequenceEGNTLRP (SEQ ID NO:35); and^ Light chain CDR3 (L-CDR3) comprising an amino acid sequence at least 80%, 85%, 90%, 95%, or 100% identical to the amino acid sequenceLQSDNMPYT (SEQ ID NO:36). In one embodiment, the anti-human CD300c antibodies, or fragments thereof, comprise: an H-CDR1 comprising the amino acid sequence of SEQ ID NO:31; ^ an H-CDR2 comprising the amino acid sequence of SEQ ID NO:32; an H-CDR3 comprising the amino acid sequence of SEQ ID NO:33; an L-CDR1 comprising the amino acid sequence of SEQ ID NO:34; an L-CDR2 comprising the amino acid sequence of SEQ ID NO:35; and an L-CDR3 comprising the amino acid sequence of SEQ ID NO:36. ^ In another aspect, the disclosure provides isolated anti-human CD300c antibodies, or fragments thereof, comprising 1, 2, 3, 4, 5, or all 6 complementarity determining regions (CDs) selected from the group consisting of: 5^ ^ Heavy chain CDR1 (H-CDR1) comprising an amino acid sequence at least 80%, 85%, 90%, 95%, or 100% identical to the amino acid sequence DYYMY (SEQ ID NO:39); Heavy chain CDR2 (H-CDR2) comprising an amino acid sequence at least 80%, 85%, 90%, 95%, or 100% identical to the amino acid sequenceTISNGGSYTYYPDSVKG^ (SEQ ID NO:40); Heavy chain CDR3 (H-CDR3) comprising an amino acid sequence at least 80%, 85%, 90%, 95%, or 100% identical to the amino acid sequenceGGDYYGNTYAY (SEQ ID NO:41); Light chain CDR1 (L-CDR1) comprising an amino acid sequence at least 80%, 85%,^ 90%, 95%, or 100% identical to the amino acid sequenceKASQSVDYDGDSYIN (SEQ ID NO:42); Light chain CDR2 (L-CDR2) comprising an amino acid sequence at least 80%, 85%, 90%, 95%, or 100% identical to the amino acid sequence AASNLES (SEQ ID NO:43); and Light chain CDR3 (L-CDR3) comprising an amino acid sequence at least 80%, 85%,^ 90%, 95%, or 100% identical to the amino acid sequenceQQSNEDPYT (SEQ ID NO:44). In one embodiment, the anti-human CD300c antibodies, or fragments thereof, comprise: an H-CDR1 comprising the amino acid sequence of SEQ ID NO:39; an H-CDR2 comprising the amino acid sequence of SEQ ID NO:40; ^ an H-CDR3 comprising the amino acid sequence of SEQ ID NO:41; an L-CDR1 comprising the amino acid sequence of SEQ ID NO:42; an L-CDR2 comprising the amino acid sequence of SEQ ID NO:43; and an L-CDR3 comprising the amino acid sequence of SEQ ID NO:44. In embodiments of any aspect of the disclosure, the wherein the antibody comprises a^ monoclonal antibody, or fragment thereof, or the antibody comprises a humanized antibody, or fragment thereof. In another embodiment, the antibody is a chimeric antibody. In one such embodiment, the heavy chain of any embodiment disclosed herein may further comprise an amino acid sequence at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%,^ 97%, 98%, 99%, or 100% identical to the amino acid sequence selected from SEQ ID NO:47 and 70-72. In another embodiment, the light chain of any embodiment disclosed herein may further comprise an amino acid sequence at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid 6^ ^ sequence selected from SEQ ID NO:48 and 73. In a further embodiment, the heavy chain or light chain comprises an amino acid sequence at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence selected from SEQ ID NO:50-61. In other embodiments, the antibodies or^ fragments thereof comprise a heavy chain and a light chain comprising an amino acid sequence at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a heavy chain-light chain pair selected from the group consisting of: SEQ ID NO:50-51; ^ SEQ ID NO:52-53; SEQ ID NO:54-55; SEQ ID NO:56-57; SEQ ID NO:58-59; and SEQ ID NO:60-61. ^ The disclosure also provides nucleic acids encoding the antibody or fragment thereof of any embodiment; vectors comprising the nucleic acid operatively linked to a suitable control sequence, host cells comprising the antibody or fragment thereof, the nucleic acid and/or the expression vector of any embodiment, and pharmaceutical compositions, comprising the antibody or fragment thereof, the nucleic acid, the vector, and/or the host cell^ of embodiment; and a pharmaceutically acceptable carrier. The disclosure also provides methods for treating cancer, comprising administering to a subject in need thereof the antibody or fragment thereof, the nucleic acid, the vector, the host cell, and/or the pharmaceutical composition of any embodiment herein, in an amount effective to treat the cancer. ^ Description of the Figures Figure 1. Chimeric anti-hERMAP antibody (human IgG1) (SEQ ID NO:50-51) blocks the inhibitory activity of hERMAP protein on T cell activation (CD69 expression on CD4 and CD8 T cells). T cells were stimulated with anti-CD3 antibody in the presence of 8^ ug/ml hERMAP protein and 25 ug/ml anti-hERMAP chimeric antibody (IgG) or control IgG. T cells were unstimulated as a negative control (blank). The percentage of CD69+ on CD4+ (A) or CD8+ T cells (B) was analyzed by flow cytometry. 7^ ^ Figure 2.^Anti-hERMAP monoclonal antibody (mAb) inhibits cancer growth in a leukemia animal model. (A) DBA/2J mice were injected subcutaneously (s.c.) with 1× 105 P388 murine leukemia cells on day 0, followed by injection of the anti- hERMAP mAb (100μg) or control (isotype) Ab (100 μg) on days 3, 5, 7, 9, and 12. (B) Tumors size was^ measured over time. The mean tumor diameter (mm3) + S.D. at the indicated time points is shown. Figure 3.^Anti-hERMAP mAb increases the survival of leukemia-bearing mice. DBA/2J mice were injected with 2× 105 P388 murine leukemia cells on day 0, followed by injection of the anti- hERMAP mAb (100μg) or control (isotype) Ab (100 μg) on days 3, 5, 7,^ 9, and 12. The survival of the mice was monitored over time. Figure 4.^Anti-hERMAP mAb inhibits tumor growth in a colon cancer animal model. (A) BALB/c mice were injected subcutaneously (s.c.) with CT 26 colon cancer cells on day 0, followed by injection of the anti- hERMAP mAb (100μg) or control (isotype) Ab (100 μg) on days 3, 5, 7, 9, and 12. (B) Tumors size was measured over time. The mean tumor^ diameter (mm3) + S.D. at the indicated time points is shown. Figure 5.^Anti-hERMAP mAb increases the survival of colon cancer-bearing mice. BALB/c mice were injected subcutaneously (s.c.) with CT 26 colon cancer cells on day 0, followed by injection of the anti- hERMAP mAb (100μg) or control (isotype) Ab (100 μg) on days 3, 5, 7, 9, and 12. The survival of the mice was monitored over time. ^ Figure 6.^Anti-TAPBPL chimeric Ab (SEQ ID NO:62-63) inhibits tumor growth in (A) melanoma and (B) colon cancer animal models. C57BL/6 or BALB/c mice were injected subcutaneously (s.c.) with B16F10 melanoma cells or CT 26 colon cancer cells on day 0, followed by injection of the anti-TAPBPL chimeric Ab (100μg) or control (isotype) Ab (100 μg) on days 3, 5, 7, 9, and 12. The melanomas and colon tumors were harvested on day 20^ and 30, respectively. The photos show the sizes of the tumors. Figure 7. Anti-hTAPBPL antibody (Ab) inhibits tumor growth in a melanoma model. (A) Syngeneic B57BL/6 mice were injected subcutaneously (s.c.) with melanoma cells. When cancers were visible and palpable, the mice were injected s.c. with graded doses of anti- hTAPBPL Ab (50, 100, and 200 μg) or control Ab. Cancer size (volume) was monitored over^ time. At the end of study, the cancer was analyzed for (B) CD4 and (C) CD8 T cells by flow cytometry. Figure 8. Anti-hTAPBPL antibody (AB) treats established cancer in a P388 leukemia model. Syngeneic DBA/2J mice were injected subcutaneously (s.c.) with P388 leukemia cells. When cancers were visible and palpable, the mice were injected s.c. with graded doses 8^ ^ of anti-hTAPBPL Ab (50, 100, and 200 μg) or control Ab. Cancer size (volume) was monitored over time. Figure 9.^Anti-TAPBPL chimeric Ab (SEQ ID NO:62-63) treatment results in increased tumor infiltrating CD4 and CD8 T cells. BALB/c mice were injected ^ subcutaneously (s.c.) with CT 26 colon cancer cells on day 0, followed by injection of the anti-TAPBPL chimeric Ab (100μg) or control (isotype) Ab (100 μg) on days 3, 5, 7, 9, and 12. The colon cancers were harvested on day 30. Tumor infiltrating CD4 and CD8 T cells were examined by immunofluorescence. Figure 10. Anti-TAPBPL Ab2 (murine precursor to SEQ ID NO:52-53) and Ab3^ (murine precursor to SEQ ID NO:54-55) neutralize T cell inhibitory activity of TAPBPL-Ig in vitro. (A) T cells from splenocytes of C57BL/6 mice were stimulated with anti-CD3 Ab in the presence of control Ig or human TAPBPL-Ig with anti-TAPBPL Ab2 (left panel), anti- TAPBPL Ab3 (right panel), or their isotype Ab. T cells were then analyzed for the expression of CD69 (an early T cell activation marker) on CD4 and CD8 T cells 24 hours later. Figures^ show statistical analysis of the percentage of CD69+cells on CD4 and CD8 T cells. The data suggest that anti-TAPBPL Ab2 and Ab3 can neutralize the inhibitory activity of TAPBPL-Ig on T cell activation. Figure 11. Anti-TAPBPL antibodies (Abs) inhibit tumor growth in a melanoma animal model. Syngeneic B57BL/6 mice were injected subcutaneously (s.c.) with B16F10^ melanoma cells. When cancers were visible and palpable, the mice were injected with anti- TAPBPL Ab2, (murine precursor to SEQ ID NO:52-53) anti-TAPBPL Ab3 (murine precursor to SEQ ID NO:54-55) (100 μg), or control isotype Ab. Cancer size (volume) was monitored over time. Figure 12. Anti-TAPBPL antibodies (Abs) inhibit tumor growth in a leukemia^ animal model. Syngeneic DBA/2J mice were injected s.c. with P388 leukemia cells. When cancers were visible and palpable, the mice were injected with anti-TAPBPL Ab2 (murine precursor to SEQ ID NO:52-53), anti-TAPBPL Ab3 (murine precursor to SEQ ID NO:54-55) (100 μg), or control isotype Ab. Cancer size (volume) was monitored over time. Figure 13 Anti-CD300c Ab2 (murine precursor to SEQ ID NO:56-57), Ab3 (murine^ precursor to SEQ ID NO:58-59), and Ab4 (murine precursor to SEQ ID NO:60-61) neutralize T cell inhibitory activity of CD300c-Ig in vitro. (A) T cells from splenocytes of C57BL/6 mice were stimulated with anti-CD3 Ab in the presence of control Ig or human CD300c-Ig with anti-CD300c Ab2 (left panel), anti-CD300c Ab3 (middle panel), anti-CD300c Ab4 (right panel), or their isotype Ab. T cells were then analyzed for the expression of CD69 (an 9^ ^ early T cell activation marker) on CD4 and CD8 T cells 24 hours later. Figures show statistical analysis of the percentage of CD69+cells on CD4 and CD8 T cells. The data suggest that anti- CD300c Ab2, Ab3, and Ab4 can neutralize the inhibitory activity of CD300c-Ig on T cell activation. ^ Figure 14. Anti-CD300c antibodies (Abs) inhibit tumor growth in a melanoma animal model. Syngeneic B57BL/6 mice were injected subcutaneously (s.c.) with B16F10 melanoma cells. When cancers were visible and palpable, the mice were injected with anti- CD300c Ab2 murine precursor to SEQ ID NO:56-57), anti-CD300c Ab3 murine precursor to SEQ ID NO:58-59) (100 μg), or control isotype Ab. Cancer size (volume) was monitored^ over time. Detailed Description As used herein and unless otherwise indicated, the terms “a” and “an” are taken to mean “one”, “at least one” or “one or more”. Unless otherwise required by context, singular^ terms used herein shall include pluralities and plural terms shall include the singular. Unless the context clearly requires otherwise, throughout the description and the claims, the words ‘comprise’, ‘comprising’, and the like are to be construed in an inclusive sense as opposed to an exclusive or exhaustive sense; that is to say, in the sense of “including, but not limited to”. Words using the singular or plural number also include the^ plural or singular number, respectively. Additionally, the words “herein,” “above” and "below" and words of similar import, when used in this application, shall refer to this application as a whole and not to any particular portions of this application. As used herein, the amino acid residues are abbreviated as follows: alanine (Ala; A), asparagine (Asn; N), aspartic acid (Asp; D), arginine (Arg; R), cysteine (Cys; C), glutamic^ acid (Glu; E), glutamine (Gln; Q), glycine (Gly; G), histidine (His; H), isoleucine (Ile; I), leucine (Leu; L), lysine (Lys; K), methionine (Met; M), phenylalanine (Phe; F), proline (Pro; P), serine (Ser; S), threonine (Thr; T), tryptophan (Trp; W), tyrosine (Tyr; Y), and valine (Val; V). All embodiments of any aspect of the invention can be used in combination, unless^ the context clearly dictates otherwise. In a first aspect, the disclosure provides isolated anti-human BTN5 (ERMAP) antibodies, or fragments thereof, comprising 1, 2, 3, 4, 5, or all 6 complementarity determining regions (CDRs) selected from the group consisting of: 10^ ^ Heavy chain CDR1 (H-CDR1) comprising an amino acid sequence at least 80%, 85%, 90%, 95%, or 100% identical to the amino acid sequenceSYYIH (SEQ ID NO: 1); Heavy chain CDR2 (H-CDR2) comprising an amino acid sequence at least 80%, 85%, 90%, 95%, or 100% identical to the amino acid sequenceWIYPGNVNTKYNEKFKG (SEQ ID^ NO: 2); Heavy chain CDR3 (H-CDR3) comprising an amino acid sequence at least 80%, 85%, 90%, 95%, or 100% identical to the amino acid sequenceGDYDGGYAMDY (SEQ ID NO: 3). Light chain CDR1 (L-CDR1) comprising an amino acid sequence at least 80%, 85%,^ 90%, 95%, or 100% identical to the amino acid sequenceRSSKSLLHSNGNTYLY (SEQ ID NO: 4); Light chain CDR2 (L-CDR2) comprising an amino acid sequence at least 80%, 85%, 90%, 95%, or 100% identical to the amino acid sequenceRMSNLAS (SEQ ID NO: 5); and Light chain CDR3 (L-CDR3) comprising an amino acid sequence at least 80%, 85%,^ 90%, 95%, or 100% identical to the amino acid sequenceMQHLEYPLT (SEQ ID NO: 6). In one embodiment, the anti-human BTN5 (ERMAP) antibody, or fragment thereof, comprises: an H-CDR1 comprising the amino acid sequence of SEQ ID NO:1; an H-CDR2 comprising the amino acid sequence of SEQ ID NO:2; ^ an H-CDR3 comprising the amino acid sequence of SEQ ID NO:3; an L-CDR1 comprising the amino acid sequence of SEQ ID NO:4; an L-CDR2 comprising the amino acid sequence of SEQ ID NO:5; and an L-CDR3 comprising the amino acid sequence of SEQ ID NO:6. As shown in the examples that follow, the disclosed anti-human Erythroid membrane-^ associated protein (BTN5 or ERMAP) antibodies, or fragments thereof, are the first antibodies shown to have the ability to neutralize the inhibitory effects of BTN5 (ERMAP) on T cells. The sequences of these antibodies have been determined, including the complementarity determining regions (CDRs) disclosed herein. As will be understood by those of skill in the art, the CDRs are the key factor in antigen-binding selectivity, and thus^ other regions of the antibody amino acid sequence may be substantially modified. In a further embodiment, the anti-human BTN5 (ERMAP) antibody, or antigen-binding fragment thereof comprises: 11^ ^ (a) a heavy chain comprising an amino acid sequence at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO 7; and/or (b) a light chain comprising an amino acid sequence at least 60%, 65%, 70%,^ 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:8. QVQLQQSGPELVKPGASVRISCKASGYTFTSYYIHWVKQRPGQGLEWIGWIYPGNVNTKYNE KFKGKATLTADKSSSTAYMQLSSLTSEDSAVYFCARGDYDGGYAMDYWGQGTSVTVSS ^ (SEQ ID NO:7; CDRs are highlighted) DIVMTQAAPSVPVTPGESVSISCRSSKSLLHSNGNTYLYWFLQRPGQSPQLLIYRMSNLASG VPDRFSGSGSGTAFTLRISRVEAEDVGVYYCMQHLEYPLTFGAGTKLELK (SEQ ID NO:8; CDRs are highlighted). ^ In another embodiment, the disclosure provides isolated anti-human TAP Binding Protein Like protein (TAPBPL) antibodies, or fragments thereof, comprising 1, 2, 3, 4, 5, or all 6 complementarity determining regions (CDRs) selected from the group consisting of: Heavy chain CDR1 (H-CDR1) comprising an amino acid sequence at least 80%,^ 85%, 90%, 95%, or 100% identical to the amino acid sequence NYWIE (SEQ ID NO:9); Heavy chain CDR2 (H-CDR2) comprising an amino acid sequence at least 80%, 85%, 90%, 95%, or 100% identical to the amino acid sequenceEILPGSGSTNYNEKFKG (SEQ ID NO:10); Heavy chain CDR3 (H-CDR3) comprising an amino acid sequence at least 80%,^ 85%, 90%, 95%, or 100% identical to the amino acid sequenceFTMARYWYFDV (SEQ ID NO:11); Light chain CDR1 (L-CDR1) comprising an amino acid sequence at least 80%, 85%, 90%, 95%, or 100% identical to the amino acid sequenceRSSTGAVTTSNYAN (SEQ ID NO:12); ^ Light chain CDR2 (L-CDR2) comprising an amino acid sequence at least 80%, 85%, 90%, 95%, or 100% identical to the amino acid sequenceGTSNRAP (SEQ ID NO:13); and 12^ ^ Light chain CDR3 (L-CDR3) comprising an amino acid sequence at least 80%, 85%, 90%, 95%, or 100% identical to the amino acid sequenceALWYSTH(F/Y)V (SEQ ID NO:14), wherein residues in parentheses are options at that position. In one embodiment, the anti-human TAPBPL antibody, or fragment thereof,^ comprises: an H-CDR1 comprising the amino acid sequence of SEQ ID NO:9; an H-CDR2 comprising the amino acid sequence of SEQ ID NO:10; an H-CDR3 comprising the amino acid sequence of SEQ ID NO:11; an L-CDR1 comprising the amino acid sequence of SEQ ID NO:12; ^ an L-CDR2 comprising the amino acid sequence of SEQ ID NO:13; and an L-CDR3 comprising the amino acid sequence of SEQ ID NO:14. In another embodiment, the L-CDR3 comprises the amino acid sequence of ALWYSTHFV (SEQ ID NO:15). As shown in the examples that follow, the disclosed anti-human TAPBPL antibodies,^ or fragments thereof, have the ability to neutralize the inhibitory effects of TAPBPL on T cells. The sequences of these antibodies have been determined, including the complementarity determining regions (CDRs) disclosed herein. In a further embodiment, the anti-human TAPBPL antibody, or antigen-binding fragment thereof comprises: (a) a heavy chain comprising an amino acid sequence at least 60%, 65%, 70%,^ 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:16; and/or (b) a light chain comprising an amino acid sequence at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 17. ^ QVQLQQSGAELMKPGASVKISCKATGYTFSNYWIEWVKQRPGHGLEWIGEILPGSGSTNYNE KFKGKATFTADTSSNTAYMQLSSLTSEDSAVYYCARFTMARYWYFDVWGAGTTVTVSS (SEQ ID NO:16; CDRs are highlighted); and/or ^ QAVVTQESALTTSPGGTVILTCRSSTGAVTTSNYANWVQEKPDHLFTGLIGGTSNRAPGVPV RFSGSLIGDKAALTITGAQTEDDAMYFCALWYSTHFVFGGGTKVTVL (SEQ ID NO:17; CDRs are highlighted). 13^ ^ In another embodiment, the isolated anti-human TAPBPL antibodies, or fragments thereof, comprise 1, 2, 3, 4, 5, or all 6 complementarity determining regions (CDRs) selected from the group consisting of: Heavy chain CDR1 (H-CDR1) comprising an amino acid sequence at least 80%,^ 85%, 90%, 95%, or 100% identical to the amino acid sequenceRYWMS (SEQ ID NO:18); Heavy chain CDR2 (H-CDR2) comprising an amino acid sequence at least 80%, 85%, 90%, 95%, or 100% identical to the amino acid sequenceEINPDSSTINYTPSLKD (SEQ ID NO:19); Heavy chain CDR3 (H-CDR3) comprising an amino acid sequence at least 80%,^ 85%, 90%, 95%, or 100% identical to the amino acid sequenceVTTVVARDWYFDV (SEQ ID NO:20); Light chain CDR1 (L-CDR1) comprising an amino acid sequence at least 80%, 85%, 90%, 95%, or 100% identical to the amino acid sequence of SEQ ID NO:12; Light chain CDR2 (L-CDR2) comprising an amino acid sequence at least 80%, 85%,^ 90%, 95%, or 100% identical to the amino acid sequence of SEQ ID NO:13; and Light chain CDR3 (L-CDR3) comprising an amino acid sequence at least 80%, 85%, 90%, 95%, or 100% identical to the amino acid sequence of SEQ ID NO:14. In one embodiment, the anti-human TAPBPL antibodies, or fragments thereof comprise: ^ an H-CDR1 comprising the amino acid sequence of SEQ ID NO:18; an H-CDR2 comprising the amino acid sequence of SEQ ID NO:19; an H-CDR3 comprising the amino acid sequence of SEQ ID NO:20; an L-CDR1 comprising the amino acid sequence of SEQ ID NO:12; an L-CDR2 comprising the amino acid sequence of SEQ ID NO:13; and^ an L-CDR3 comprising the amino acid sequence of SEQ ID NO:14. In one embodiment, L-CDR3 comprises the amino acid sequence ofALWYSTHYV (SEQ ID NO:49). In a further embodiment, the anti-human TAPBPL antibodies, or fragments thereof,^ comprise: (a) a heavy chain comprising an amino acid sequence at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:21; and/or 14^ ^ (b) a light chain comprising an amino acid sequence at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:22. ^ EVKLLQSGGGLVQPGGSLKLSCAASGFDFSRYWMSWVRQAPGKGLEWIGEINPDSSTINYTP SLKDKFIISRDNAKNTLYLQMSKVRSEDTALYYCASVTTVVARDWYFDVWGAGTTVTVSS (SEQ ID NO:21; CDRs are highlighted); and/or QAVVTQESALTTSPGGTVILTCRSSTGAVTTSNYANWVQEKPDHLFTGLIGGTSNRAPGVPV ^ RFSGSLIGDKAALTITGAQTEDDAMYFCALWYSTHYVFGGGTKVTVL (SEQ ID NO:22; CDRs are highlighted). In another aspect, the disclosure provides anti-human CD300c antibodies, or fragments thereof, comprising 1, 2, 3, 4, 5, or all 6 complementarity determining regions^ (CDs) selected from the group consisting of: Heavy chain CDR1 (H-CDR1) comprising an amino acid sequence at least 80%, 85%, 90%, 95%, or 100% identical to the amino acid sequenceGYNMN (SEQ ID NO:23); Heavy chain CDR2 (H-CDR2) comprising an amino acid sequence at least 80%, 85%, 90%, 95%, or 100% identical to the amino acid sequenceNIDPYYGGTSYNQKFKG^ (SEQ ID NO:24); Heavy chain CDR3 (H-CDR3) comprising an amino acid sequence at least 80%, 85%, 90%, 95%, or 100% identical to the amino acid sequenceSGYYYAMDY (SEQ ID NO:25); Light chain CDR1 (L-CDR1) comprising an amino acid sequence at least 80%, 85%,^ 90%, 95%, or 100% identical to the amino acid sequenceKASQNVGTAVA (SEQ ID NO:26); Light chain CDR2 (L-CDR2) comprising an amino acid sequence at least 80%, 85%, 90%, 95%, or 100% identical to the amino acid sequenceSASNRYT (SEQ ID NO:27); and Light chain CDR3 (L-CDR3) comprising an amino acid sequence at least 80%, 85%, 90%, 95%, or 100% identical to the amino acid sequenceQQYSSYPYT (SEQ ID NO:28).^ In one embodiment, the anti-human CD300c antibodies, or fragments thereof, comprise: an H-CDR1 comprising the amino acid sequence of SEQ ID NO:23; an H-CDR2 comprising the amino acid sequence of SEQ ID NO:24; an H-CDR3 comprising the amino acid sequence of SEQ ID NO:25; 15^ ^ an L-CDR1 comprising the amino acid sequence of SEQ ID NO:26; an L-CDR2 comprising the amino acid sequence of SEQ ID NO:27; and an L-CDR3 comprising the amino acid sequence of SEQ ID NO:28. ^ As shown in the examples that follow, the disclosed anti-human CD300c antibodies, or fragments thereof, have the ability to neutralize the inhibitory effects of CD300c on T cells. The sequences of these antibodies have been determined, including the complementarity determining regions (CDRs) disclosed herein. In a further embodiment, the anti-human CD300c antibody, or antigen-binding fragment thereof comprises: ^ In one embodiment, the anti-human CD300c antibody, or fragment thereof, comprises: (a) a heavy chain comprising an amino acid sequence at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:29; and/or ^ (b) a light chain comprising an amino acid sequence at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:30). EFQLQQSGPELEKPGASVKISCKASGYSFTGYNMNWVKQSNGKSLEWIGNIDPYYGGTSYNQ ^ KFKGKATLTVDKSSSTAYMQLKSLTSEDSAVYYCARSGYYYAMDYWGQGTSVTVSS (SEQ ID NO:29; CDRs are highlighted) DIVMTQSQKFMSTSVGDRVSITCKASQNVGTAVAWYQQKPGQSPKLLIYSASNRYTGVPDRF TGSGSGTDFTLTISNMQSEDLADYFCQQYSSYPYTFGGGTKLEIK (SEQ ID NO:30;^ CDRs are highlighted). In another embodiment, the anti-human CD300c antibodies, or fragments thereof, comprise 1, 2, 3, 4, 5, or all 6 complementarity determining regions (CDs) selected from the group consisting of: Heavy chain CDR1 (H-CDR1) comprising an amino acid sequence at least 80%,^ 85%, 90%, 95%, or 100% identical to the amino acid sequenceDYYMK (SEQ ID NO:31); Heavy chain CDR2 (H-CDR2) comprising an amino acid sequence at least 80%, 85%, 90%, 95%, or 100% identical to the amino acid sequenceDINPNNGDTFYNQKFKG (SEQ ID NO:32); 16^ ^ Heavy chain CDR3 (H-CDR3) comprising an amino acid sequence at least 80%, 85%, 90%, 95%, or 100% identical to the amino acid sequenceGGMVTTAMDY (SEQ ID NO:33); Light chain CDR1 (L-CDR1) comprising an amino acid sequence at least 80%, 85%,^ 90%, 95%, or 100% identical to the amino acid sequenceRTITDIDDDMN (SEQ ID NO:34); Light chain CDR2 (L-CDR2) comprising an amino acid sequence at least 80%, 85%, 90%, 95%, or 100% identical to the amino acid sequenceEGNTLRP (SEQ ID NO:35); and Light chain CDR3 (L-CDR3) comprising an amino acid sequence at least 80%, 85%, 90%, 95%, or 100% identical to the amino acid sequenceLQSDNMPYT (SEQ ID NO:36).^ In one embodiment, the anti-human CD300c antibodies, or fragment thereof, comprise: an H-CDR1 comprising the amino acid sequence of SEQ ID NO:31; an H-CDR2 comprising the amino acid sequence of SEQ ID NO:32; an H-CDR3 comprising the amino acid sequence of SEQ ID NO:33; ^ an L-CDR1 comprising the amino acid sequence of SEQ ID NO:34; an L-CDR2 comprising the amino acid sequence of SEQ ID NO:35; and an L-CDR3 comprising the amino acid sequence of SEQ ID NO:36. In a further embodiment, the anti-human CD300c antibody, or antigen-binding^ fragment thereof comprises: (a) a heavy chain comprising an amino acid sequence at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:37; and/or (b) a light chain comprising an amino acid sequence at least 60%, 65%, 70%,^ 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:38. EVQLQQSGPELVKPGASVKMSCKASGYTFTDYYMKWVKQSHGKSLEWIGDINPNNGDTFYNQ KFKGKATLTVDKSSSTAYMQLNSLTSEDSAVYYCATGGMVTTAMDYWGQGTSVTVSS ^ (SEQ ID NO:37; CDRs are highlighted); and/or ETTVTQSPASLSVATGEKVTIRCRTITDIDDDMNWYQQKPGEPPKLLISEGNTLRPGVPSRF SSSGYGTDFVFTIENTLSEDVADYYCLQSDNMPYTFGGGTKLEIK 17^ ^ (SEQ ID NO:38; CDRs are highlighted). In a further embodiment, the anti-human CD300c antibodies, or fragments thereof, comprise 1, 2, 3, 4, 5, or all 6 complementarity determining regions (CDs) selected from the^ group consisting of: Heavy chain CDR1 (H-CDR1) comprising an amino acid sequence at least 80%, 85%, 90%, 95%, or 100% identical to the amino acid sequenceDYYMY^(SEQ ID NO:39); Heavy chain CDR2 (H-CDR2) comprising an amino acid sequence at least 80%, 85%, 90%, 95%, or 100% identical to the amino acid sequenceTISNGGSYTYYPDSVKG^ (SEQ ID NO:40); Heavy chain CDR3 (H-CDR3) comprising an amino acid sequence at least 80%, 85%, 90%, 95%, or 100% identical to the amino acid sequenceGGDYYGNTYAY (SEQ ID NO:41); Light chain CDR1 (L-CDR1) comprising an amino acid sequence at least 80%, 85%,^ 90%, 95%, or 100% identical to the amino acid sequenceKASQSVDYDGDSYIN (SEQ ID NO:42); Light chain CDR2 (L-CDR2) comprising an amino acid sequence at least 80%, 85%, 90%, 95%, or 100% identical to the amino acid sequenceAASNLES (SEQ ID NO:43); and Light chain CDR3 (L-CDR3) comprising an amino acid sequence at least 80%, 85%,^ 90%, 95%, or 100% identical to the amino acid sequenceQQSNEDPYT (SEQ ID NO:44). In one embodiment, the anti-human CD300c antibodies, or fragments thereof, comprise: an H-CDR1 comprising the amino acid sequence of SEQ ID NO:39; an H-CDR2 comprising the amino acid sequence of SEQ ID NO:40; ^ an H-CDR3 comprising the amino acid sequence of SEQ ID NO:41; an L-CDR1 comprising the amino acid sequence of SEQ ID NO:42; an L-CDR2 comprising the amino acid sequence of SEQ ID NO:43; and an L-CDR3 comprising the amino acid sequence of SEQ ID NO:44. ^ In a further embodiment, the anti-human CD300c antibody, or antigen-binding fragment thereof comprises (a) a heavy chain comprising an amino acid sequence at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:45; and/or 18^ ^ (b) a light chain comprising an amino acid sequence at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:46. ^
Figure imgf000020_0001
(SEQ ID NO:45; CDRs are highlighted) DIVLTQSPASLAVSLGQRATISCKASQSVDYDGDSYINWYQQKPGQPPKLLIYAASNLESGI ^ PARFSGSGSGTDFTLNIHPVEEEDAAAYYCQQSNEDPYTFGGGTKLEIK (SEQ ID NO:46; CDRs are highlighted). As used herein, the term "antibody includes antibodies having at least one antigen- binding domain and includes monoclonal antibodies fragments and/or variants thereof^ including recombinant polypeptides, fusion proteins, and immunoconjugates. Thus, the terms "antibody," "antibody fragment," and "antibody variant" are used interchangeably herein. Examples of antibody fragments of the invention include, but are not limited to, the Fab fragment, consisting of VL, VH, CL and CHI domains; the Fc fragment, consisting of the VH and CHI domains; the Fv fragment consisting of the VL and VH; the dAb fragment ^ consisting of a VH domain; isolated CDR regions; F(ab')2 a bivalent fragment comprising two linked Fab fragments; and single chain Fv molecules (scFv).. The antibodies may be chimeric, humanized, or fully human antibodies. In one specific embodiment, the antibody is a monoclonal antibody, or a fragment thereof. In one embodiment, the antibodies may be chimeric, for example, including a human^ heavy chain and/or light chain constant region. Any human heavy chain constant region (such as IgG1, IgG2, IgG3, and IgG4) and/or light chain constant region (such as IgG kappa light chain or IgG lambda light chain) may be used. In one embodiment, the heavy chain of any embodiment disclosed herein may comprise an amino acid sequence at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%^ identical to the amino acid sequence selected from SEQ ID NO:47 and 70-72 ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGL YSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVF LFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREE QYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE 19^ ^ EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:47; Human IgG1 heavy chain constant region) ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGL ^ YSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTVERKCCVECPPCPAPPVAGPSVFLFPP KPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLT VVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQVSLTCLV KGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEA LHNHYTQKSLSLSPGK (SEQ ID NO:70 Human IgG2 heavy chain ^ constant region) ASTKGPSVFPLAPCSRSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGL YSLSSVVTVPSSSLGTQTYTCNVNHKPSNTKVDKRVELKTPLGDTTHTCPRCPEPKSCDTPP PCPRCPEPKSCDTPPPCPRCPEPKSCDTPPPCPRCPAPELLGGPSVFLFPPKPKDTLMISRT ^ PEVTCVVVDVSHEDPEVQFKWYVDGVEVHNAKTKPREEQYNSTFRVVSVLTVLHQDWLNGKE YKCKVSNKALPAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVE WESSGQPENNYNTTPPMLDSDGSFFLYSKLTVDKSRWQQGNIFSCSVMHEALHNRFTQKSLS LSPGK (SEQ ID NO: 71 Human IgG3 heavy chain constant region) ^ ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGL YSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSVFLFP PKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVL TVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCL VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHE ^ ALHNHYTQKSLSLSLGK (SEQ ID NO:72 Human IgG4 heavy chain constant region) In another embodiment, the light chain of any embodiment disclosed herein may comprise an amino acid sequence at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%,^ 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence selected from SEQ ID NO:48 and 73. TVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKD STYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC (SEQ ID NO:48; Human IgG1 kappa light chain constant region) 20^ ^ ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGL YSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSVFLFP PKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVL ^ TVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCL VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHE ALHNHYTQKSLSLSLGK (SEQ ID NO:73 Human immunoglobulin lambda light chain constant region) ^ In various further embodiments, the chimeric antibodies may comprise chimeric heavy chains and/or light chains comprising an amino acid sequence at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence selected from SEQ ID NO:50-65, the sequences of which are provided in Table 1. In other embodiments, the antibody, or antigen-binding fragment thereof^ comprises a heavy chain and a light chain comprising an amino acid sequence at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of a heavy chain-light chain pair selected from the group consisting of: SEQ ID NO:50-51; ^ SEQ ID NO:52-53; SEQ ID NO:54-55; SEQ ID NO:56-57; SEQ ID NO:58-59; SEQ ID NO:60-61; ^ SEQ ID NO:62-63; and SEQ ID NO:64-65. Table 1
Figure imgf000022_0001
21^ ^
Figure imgf000023_0001
22^ ^
Figure imgf000024_0001
In one embodiment, variability compared to the reference sequence is present only outside the CDRs. In some embodiments, the antibodies or fragments thereof are conjugated to one or^ more agents selected from the group including an additional therapeutic agent, such as a chemotherapeutic agent. A "chemotherapeutic agent" is a chemical compound useful in the treatment of cancer. Examples of chemotherapeutic agents include alkylating agents such as thiotepa and cyclosphosphamide; alkyl sulfonates such as busulfan, improsulfan and 23^ ^ piposulfan; aziridines such as benzodopa, carboquone, meturedopa, and uredopa; ethylenimines and methylamelamines including altretamine, triethylenemelamine, triethylenephosphoramide, triethylenethiophosphoramide and trimethylolomelamine; acetogenins (especially bullatacin and bullatacinone); a camptothecin (including the synthetic^ analogue topotecan); bryostatin; callystatin; CC-1065 (including its adozelesin, carzelesin and bizelesin synthetic analogues); cryptophycins (particularly cryptophycin 1 and cryptophycin 8); dolastatin; duocarmycin (including the synthetic analogues, KW-2189 and CB1-TM1); eleutherobin; pancratistatin; a sarcodictyin; spongistatin; nitrogen mustards such as chlorambucil, chlornaphazine, cholophosphamide, estramustine, ifosfamide, ^ mechlorethamine, mechlorethamine oxide hydrochloride, melphalan, novembichin, phenesterine, prednimustine, trofosfamide, uracil mustard; nitrosureas such as carmustine, chlorozotocin, fotemustine, lomustine, nimustine, and ranimustine; antibiotics such as the enediyne antibiotics (e. g., calicheamicin, especially calicheamicin gamma 11 and calicheamicin omega 11 (see, e.g., Agnew, Chem Intl. Ed. Engl., 33: 183-186 (1994)); ^ dynemicin, including dynemicin A; bisphosphonates, such as clodronate; an esperamicin; as well as neocarzinostatin chromophore and related chromoprotein enediyne antibiotic chromophores), aclacinomysins, actinomycin, authramycin, azaserine, bleomycins, cactinomycin, carabicin, carminomycin, carzinophilin, chromomycinis, dactinomycin, daunorubicin, detorubicin, 6-diazo-5-oxo-L-norleucine, doxorubicin (including morpholino-^ doxorubicin, cyanomorpholino-doxorubicin, 2-pyrrolino-doxorubicin and deoxydoxorubicin), epirubicin, esorubicin, idarubicin, marcellomycin, mitomycins such as mitomycin C, mycophenolic acid, nogalamycin, olivomycins, peplomycin, potfiromycin, puromycin, quelamycin, rodorubicin, streptonigrin, streptozocin, tubercidin, ubenimex, zinostatin, zorubicin; anti-metabolites such as methotrexate and 5-fluorouracil (5-FU); folic acid^ analogues such as denopterin, methotrexate, pteropterin, trimetrexate; purine analogs such as fludarabine, 6-mercaptopurine, thiamiprine, thioguanine; pyrimidine analogs such as ancitabine, azacitidine, 6-azauridine, carmofur, cytarabine, dideoxyuridine, doxifluridine, enocitabine, floxuridine; androgens such as calusterone, dromostanolone propionate, epitiostanol, mepitiostane, testolactone; anti-adrenals such as aminoglutethimide, mitotane,^ trilostane; folic acid replenisher such as frolinic acid; aceglatone; aldophosphamide glycoside; aminolevulinic acid; eniluracil; amsacrine; bestrabucil; bisantrene; edatraxate; defofamine; demecolcine; diaziquone; elfornithine; elliptinium acetate; an epothilone; etoglucid; gallium nitrate; hydroxyurea; lentinan; lonidainine; maytansinoids such as maytansine and ansamitocins; mitoguazone; mitoxantrone; mopidanmol; nitraerine; 24^ ^ pentostatin; phenamet; pirarubicin; losoxantrone; podophyllinic acid; 2-ethylhydrazide; procarbazine; polysaccharide complex (JHS Natural Products, Eugene, Oreg.); razoxane; rhizoxin; sizofiran; spirogermanium; tenuazonic acid; triaziquone; 2,2',22''- trichlorotriethylamine; trichothecenes (especially T-2 toxin, verracurin A, roridin A and^ anguidine); urethan; vindesine; dacarbazine; mannomustine; mitobronitol; mitolactol; pipobroman; gacytosine; arabinoside ("Ara-C"); cyclophosphamide; thiotepa; taxoids, e.g., paclitaxel, ABRAXANE® Cremophor-free, albumin-engineered nanoparticle formulation of paclitaxel (American Pharmaceutical Partners, Schaumberg, Ill.), and doxetaxel; chloranbucil; gemcitabine; 6-thioguanine; mercaptopurine; methotrexate; platinum analogs^ such as cisplatin and carboplatin; vinblastine; platinum; etoposide (VP-16); ifosfamide; mitoxantrone; vincristine; vinorelbine; novantrone; teniposide; edatrexate; daunomycin; aminopterin; xeloda; ibandronate; CPT-11; topoisomerase inhibitor RFS 2000; difluorometlhylornithine (DMFO); retinoids such as retinoic acid; capecitabine; and pharmaceutically acceptable salts, acids or derivatives of any of the above. Also included in^ the definition are proteasome inhibitors such as bortezomib (Velcade), BCL-2 inhibitors, IAP antagonists (e.g. Smac mimics/xIAP and cIAP inhibitors such as certain peptides, pyridine compounds such as (S)--N-{6-benzo[1,3]dioxol-5-yl-1-[5-(4-fluoro-benzoyl)-pyridin-3- ylmethy- l]-2-oxo-1,2-dihydro-pyridin-3-yl}-2-methylamino-propionamide, xIAP antisense), HDAC inhibitors (HDACI) and kinase inhibitors (Sorafenib). ^ ^ In other embodiments, the antibodies or fragments thereof are linked to a detectable label, such as a radiolabel, an enzyme, a fluorescent label, a luminescent label, a bioluminescent label, a magnetic label, and/or biotin. In some embodiments, the agent and/or detectable label is conjugated directly to the antibodies or fragments thereof. In other embodiments, the agent and/or detectable label is^ conjugated to the antibodies or fragments thereof via a linker. In another aspect, the present disclosure provides nucleic acids encoding the antibodies or fragments thereof of any aspect or embodiment of the invention. The nucleic acid sequence may comprise RNA or DNA. Such nucleic acid sequences may comprise additional sequences useful for promoting expression and/or purification of the encoded^ protein, including but not limited to polyA sequences, modified Kozak sequences, and sequences encoding epitope tags, export signals, and secretory signals, nuclear localization signals, and plasma membrane localization signals. It will be apparent to those of skill in the art, based on the teachings herein, what nucleic acid sequences will encode the antibodies or fusion molecules disclosed herein. 25^ ^ In a further aspect, the present disclosure provides nucleic acid expression vectors comprising the nucleic acid of any embodiment of the disclosure operatively linked to a suitable control sequence. "Recombinant expression vector" includes vectors that operatively link a nucleic acid coding region or gene to any control sequences capable of effecting^ expression of the gene product. “Control sequences” operably linked to the nucleic acid sequences of the disclosure are nucleic acid sequences capable of effecting the expression of the nucleic acid molecules. The control sequences need not be contiguous with the nucleic acid sequences, so long as they function to direct the expression thereof. Thus, for example, intervening untranslated yet transcribed sequences can be present between a promoter^ sequence and the nucleic acid sequences and the promoter sequence can still be considered "operably linked" to the coding sequence. Other such control sequences include, but are not limited to, polyadenylation signals, termination signals, and ribosome binding sites. Such expression vectors can be of any type known in the art, including but not limited plasmid and viral-based expression vectors. The control sequence used to drive expression of the^ disclosed nucleic acid sequences in a mammalian system may be constitutive (driven by any of a variety of promoters, including but not limited to, CMV, SV40, RSV, actin, EF) or inducible (driven by any of a number of inducible promoters including, but not limited to, tetracycline, ecdysone, steroid-responsive. The expression vector must be replicable in the host organisms either as an episome or by integration into host chromosomal DNA. In one,^ the expression vector comprises a plasmid; in another embodiment a viral vector, including but not limited to adenoviral vectors or rAAV vectors. In another aspect, the present disclosure provides recombinant host cells comprising the antibodies or fragments thereof, nucleic acids, and/or nucleic acid expression vectors of the disclosure. The host cells can be either prokaryotic or eukaryotic. The cells can be^ transiently or stably transfected or transduced. Such transfection and transduction of expression vectors into prokaryotic and eukaryotic cells can be accomplished via any suitable technique. A method of producing the antibodies or fragments thereof is also provided herein. The method comprises the steps of (a) culturing a host according to this aspect of the disclosure under conditions conducive to the expression of the antibodies or fragments^ thereof, and (b) optionally, recovering the expressed antibodies or fragments thereof. The expressed antibodies or fragments thereof can be recovered from the cell free extract, cell pellet, or recovered from the culture medium. In a further aspect, the present disclosure provides pharmaceutical compositions, comprising the antibodies or fragments thereof, nucleic acids, nucleic acid expression 26^ ^ vectors, or recombinant host cells, of any aspect or embodiment of the disclosure, and a pharmaceutically acceptable carrier. The pharmaceutical compositions of the disclosure can be used, for example, in the methods of the disclosure. The pharmaceutical composition may comprise in addition to the antibodies or fragments thereof, nucleic acids, etc. of the ^ disclosure (a) a lyoprotectant; (b) a surfactant; (c) a bulking agent; (d) a tonicity adjusting agent; (e) a stabilizer; (f) a preservative and/or (g) a buffer. In some embodiments, the buffer in the pharmaceutical composition is a Tris buffer, a histidine buffer, a phosphate buffer, a citrate buffer or an acetate buffer. The pharmaceutical composition may also include a lyoprotectant, e.g. sucrose, sorbitol or trehalose. In certain^ embodiments, the pharmaceutical composition includes a preservative e.g. benzalkonium chloride, benzethonium, chlorohexidine, phenol, m-cresol, benzyl alcohol, methylparaben, propylparaben, chlorobutanol, o-cresol, p-cresol, chlorocresol, phenylmercuric nitrate, thimerosal, benzoic acid, and various mixtures thereof. In other embodiments, the pharmaceutical composition includes a bulking agent, like glycine. In yet other embodiments,^ the pharmaceutical composition includes a surfactant e.g., polysorbate-20, polysorbate-40, polysorbate- 60, polysorbate-65, polysorbate-80 polysorbate-85, poloxamer-188, sorbitan monolaurate, sorbitan monopalmitate, sorbitan monostearate, sorbitan monooleate, sorbitan trilaurate, sorbitan tristearate, sorbitan trioleaste, or a combination thereof. The pharmaceutical composition may also include a tonicity adjusting agent, e.g., a compound^ that renders the formulation substantially isotonic or isoosmotic with human blood. Exemplary tonicity adjusting agents include sucrose, sorbitol, glycine, methionine, mannitol, dextrose, inositol, sodium chloride, arginine and arginine hydrochloride. In other embodiments, the pharmaceutical composition additionally includes a stabilizer, e.g., a molecule which, when combined with a protein of interest substantially prevents or reduces^ chemical and/or physical instability of the protein of interest in lyophilized or liquid form. Exemplary stabilizers include sucrose, sorbitol, glycine, inositol, sodium chloride, methionine, arginine, and arginine hydrochloride. The antibodies or fragments thereof, nucleic acids, etc. of the disclosure may be the sole active agent in the pharmaceutical composition, or the composition may further comprise^ one or more other active agents suitable for an intended use. The pharmaceutical compositions described herein generally comprise a combination of a therapeutic described herein and a pharmaceutically acceptable carrier, diluent, or excipient. Such compositions are substantially free of non-pharmaceutically acceptable components, i.e., contain amounts of non-pharmaceutically acceptable components lower 27^ ^ than permitted by US regulatory requirements at the time of filing this application. In some embodiments of this aspect, if the compound is dissolved or suspended in water, the composition further optionally comprises an additional pharmaceutically acceptable carrier, diluent, or excipient. ^ In another aspect, the disclosure provides methods for treating cancer, comprising administering to a subject in need thereof the antibody or fragment thereof, the nucleic acid, the vector, the host cell, and/or the pharmaceutical composition of any embodiment or combination of embodiments herein, in an amount effective to treat the cancer. The methods may be used to treat any suitable cancer. In various non-limiting^ embodiments, the cancer may be selected from the group consisting of breast cancer, lung cancer, colon cancer, melanoma, prostate cancer, leukemia, neuroblastoma, liver, lymphoma, cervical cancer, ovarian cancer, gastric cancer, and esophageal cancer, etc. Tumor progression is often accompanied by profound immune suppression that interferes with an effective antitumor response and tumor elimination. In order to elicit^ protective immunity to cancer, and to prevent an overactive immune system, immune responses need to be tightly controlled by immune cell stimulatory and inhibitory molecules. Many cancers protect themselves from the immune system by producing inhibitory molecules to inhibit T cell function. The inventors have identified CD300c, BTN5, and TAPBPL, as targets for treating cancer. ^ As used herein, the term “treat,” “treatment,” or “treating,” means to reverse, alleviate, ameliorate, inhibit, slow down or stop the progression or severity of a symptom or condition of the disorder being treated. The term “treating” includes reducing or alleviating at least one adverse effect or symptom of a condition. Treatment is generally “effective” if one or more symptoms are reduced. Alternatively, treatment is “effective” if the progression of a^ condition is reduced or halted. That is, “treatment” may include not just the improvement of symptoms, but also a cessation or slowing of progress or worsening of symptoms that would be expected in the absence of treatment. Beneficial or desired clinical results include, but are not limited to, alleviation of one or more symptom(s), diminishment of extent of the deficit, stabilized (i.e., not worsening) state of a tumor or malignancy; delay or slowing of tumor^ growth and/or metastasis, and an increased lifespan as compared to that expected in the absence of treatment. As used herein, the term “administering,” refers to the placement of a therapeutic into a subject by a method or route deemed appropriate. The therapeutic can be administered by any appropriate route which results in an effective treatment in the subject including orally, 28^ ^ parentally, by inhalation spray, rectally, or topically in dosage unit formulations containing conventional pharmaceutically acceptable carriers, adjuvants, and vehicles. The term parenteral as used herein includes, subcutaneous, intravenous, intra-arterial, intramuscular, intrasternal, intratendinous, intraspinal, intracranial, intrathoracic, infusion techniques or^ intraperitoneal administration. Dosage regimens can be adjusted to provide the optimum desired response (e.g., a therapeutic response). A suitable dosage range may, for instance, be 0.1 ug/kg-100 mg/kg body weight; alternatively, it may be 0.5 ug/kg to 50 mg/kg; 1 ug/kg to 25 mg/kg, or 5 ug/kg to 10 mg/kg body weight. The therapeutic can be delivered in a single bolus, or may be administered more than once (e.g., 2, 3, 4, 5, or more times) as determined^ by attending medical personnel. As used herein, the phrase “amount effective” or “the like refers to an amount that provides a therapeutic benefit in the treatment, of cancer or autoimmune disease. Determination of a therapeutically effective amount is well within the capability of those skilled in the art. Generally, a therapeutically effective amount can vary with the subject's^ history, age, condition, sex, as well as the severity and type of the medical condition in the subject, and administration of other pharmaceutically active agents. Examples Generation of human and mouse chimeric antibodies (Abs) against human ERMAP,^ TAPBPL and CD300c. Murine monoclonal antibodies (mAbs) of the disclosure were generated against human ERMAP, TAPBPL and CD300c, and shown to enhance antitumor immunity and inhibit tumor growth in animal models (Figures 10-14). The hybridomas that produce the murine mAbs were sequenced, and chimeric Abs in which the murine variable domains of^ each mAb are linked to human constant regions were generated (SEQ ID NO:50-65). Genes for the murine heavy chain variable domains were cloned into a pFUSEss-CHIg-hG1 vector (from InvivoGen) that contains the heavy chain constant regions of human IgG1. Genes for the murine light chain variable domains were cloned into a pFUSEss-CLg-hk vector (from InvivoGen) that contains the light chain constant regions of human IgG. The two vectors^ were then co-transfected into HEK-293 cells to produce each chimeric Ab, which was then purified from the supernatant of the cells by Protein G SepharoseTM 4. Anti-hERMAP and Anti-TAPBPL promote an antitumor T cell response. 29^ ^ Functional studies were performed for the chimeric Abs. The anti-ERMAP chimeric Ab (SEQ ID NO:50-51) was demonstrated to neutralize the inhibitory activity of ERMAP-Ig on T cell activation (reduced CD69 expression on CD4 and CD8 T cells) (Figure 1). T cells were stimulated with anti-CD3 antibody in the presence of 8 μg/ml hERMAP protein and 25^ μg/ml anti-hERMAP chimeric antibody or control IgG. Flow cytometry analysis quantification (Figure 1A) demonstrated reduced CD69 expression on CD4+ T cells. Flow cytometry analysis quantification (Figure 1B) demonstrated reduced CD69 expression on CD8+ T cells. CD4+ T cells and CD8+ T cells infiltrate tumors to mediate an antitumor immune^ response (Tay et al. Cancer Gene Ther 28: 5-17 (2021)). Anti-TAPBPL chimeric Ab (SEQ ID NO: 62-63) treatment increased tumor infiltrating CD4+ T cells and CD8+ T cells (Figure 9). BALB/c mice were injected subcutaneously (s.c.) with CT 26 colon cancer cells on day 0, followed by injection of the anti-TAPBPL chimeric Ab (100μg) or control (isotype) Ab (100μg) on days 3, 5, 7, 9, and 12. The colon cancers were harvested on day 30. ^ Immunofluorescent staining for tumor infiltrating CD4+ T cells and CD8+ T cells demonstrated increases in both cell types over control with anti-TAPBPL chimeric Ab treatment. Anti-hERMAP inhibits tumor growth and increase survival. ^ Anti-hERMAP monoclonal antibody was tested in a leukemia animal model (Figure 2). DBA/2J mice were injected subcutaneously (s.c.) with 1× 105 P388 murine leukemia cells on day 0, followed by injection of the anti- hERMAP mAb (100μg) or control (isotype) Ab (100 μg) on days 3, 5, 7, 9, and 12 (Figure 2A). Tumors size was measured over time. The mean tumor diameter (mm3) + S.D. at the indicated time points is shown in Figure 2B.^ Treatment with anti-hERMAP inhibited tumor growth compared with control starting at day 9 and through day 15. Survival of leukemia-bearing mice treated with anti-hERMAP was compared with control (Figure 3). DBA/2J mice were injected with 2× 105 P388 murine leukemia cells on day 0, followed by injection of the anti- hERMAP mAb (100μg) or control (isotype) Ab (100^ μg) on days 3, 5, 7, 9, and 12. The graph shows a Kaplan-Meier curve for the survival of control treated versus anti-hERMAP treated leukemia-bearing mice. The survival of the mice was monitored over time. Treatment with anti-hERMAP increased the survival of leukemia- bearing mice compared to control with 100% mortality in the control mice by day 22 and about 40% mortality at the same time point for anti-hERMAP treated mice. 30^ ^ Anti-hERMAP mAb was tested in a colon cancer animal model (Figure 4). BALB/c mice were injected subcutaneously (s.c.) with CT 26 colon cancer cells on day 0, followed by injection of the anti- hERMAP mAb (100μg) or control (isotype) Ab (100 μg) on days 3, 5, 7, 9, and 12 (Figure 4A). Tumors size was measured over time. The mean tumor diameter^ (mm3) + S.D. at the indicated time points is shown (Figure 4B). Treatment with anti- hERMAP mAb inhibited tumor growth compared with control starting at day 9 and through day 24 (Figure 4B). Additionally, we assessed survival of colon cancer-bearing mice treated with anti- hERMAP compared with control (Figure 5). BALB/c mice were injected subcutaneously^ (s.c.) with CT 26 colon cancer cells on day 0, followed by injection of the anti- hERMAP mAb (100μg) or control (isotype) Ab (100 μg) on days 3, 5, 7, 9, and 12. The survival of the mice was monitored over time. Treatment with anti-hERMAP increased survival of colon cancer-bearing mice compared to control with 100% mortality at day 30 for the control mice and 5% mortality at the same time point for the anti-hERMAP treated mice. ^ Antibodies against TAPBPL inhibits tumor growth and promotes tumor infiltration. The impact of anti-TAPBPL on malignancy growth/progression was also assessed. Anti-TAPBPL chimeric Ab (SEQ ID NO:62-63) inhibited tumor growth in melanoma (Figure 6A) and colon cancer animal models (Figure 6B). C57BL/6 or BALB/c mice were^ injected subcutaneously (s.c.) with B16F10 melanoma cells or CT 26 colon cancer cells on day 0, followed by injection of the anti-TAPBPL chimeric Ab (100μg) or control (isotype) Ab (100 μg) on days 3, 5, 7, 9, and 12. The melanomas and colon cancers were harvested on day 20 and 30, respectively. The top photo shows reduced melanoma tumor sizes with anti- TAPBPL chimeric Ab treatment compared to control. The bottom photo shows reduced colon^ tumor sizes with anti-TAPBPL chimeric Ab treatment compared to control. Additionally, anti-hTAPBPL was tested in a melanoma model (Figure 7). Syngeneic B57BL/6 mice were injected subcutaneously (s.c.) with melanoma cells. When cancers were visible and palpable, the mice were injected s.c. with graded doses of anti-hTAPBPL Ab (50, 100, and 200 μg) or control Ab. Anti-hTAPBPL inhibited tumor growth, as seen by the tumor^ volume over time, in a dose dependent fashion (Figure 7A). At the end of study, the tumors were analyzed for CD4 and CD8 T cells by flow cytometry. Anti-hTAPBPL increased both CD4+ T cells (Figure 7B) and CD8+ T cells (Figure 7C) in the tumors, which are involved in tumor infiltration, compared with control. 31^ ^ Anti-hTAPBPL was then tested in an established cancer leukemia model (Figure 8). Syngeneic DBA/2J mice were injected subcutaneously (s.c.) with P388 leukemia cells. When cancers were visible and palpable, the mice were injected s.c. with graded doses of anti- hTAPBPL Ab (50, 100, and 200 μg) or control Ab. The data demonstrated that anti-^ hTAPBPL treats established cancer in a leukemia model as shown by the slowing in growth of tumor volume over time. 32^ ^

Claims

I claim 1. An isolated anti-human BTN5 (ERMAP) antibody, or fragment thereof, comprising 1, 2, 3, 4, 5, or all 6 complementarity determining regions (CDRs) selected from the group consisting of: ^ Heavy chain CDR1 (H-CDR1) comprising an amino acid sequence at least 80%, 85%, 90%, 95%, or 100% identical to the amino acid sequence SYYIH (SEQ ID NO: 1); Heavy chain CDR2 (H-CDR2) comprising an amino acid sequence at least 80%, 85%, 90%, 95%, or 100% identical to the amino acid sequenceWIYPGNVNTKYNEKFKG (SEQ ID NO: 2); ^ Heavy chain CDR3 (H-CDR3) comprising an amino acid sequence at least 80%, 85%, 90%, 95%, or 100% identical to the amino acid sequence GDYDGGYAMDY (SEQ ID NO: 3). Light chain CDR1 (L-CDR1) comprising an amino acid sequence at least 80%, 85%, 90%, 95%, or 100% identical to the amino acid sequenceRSSKSLLHSNGNTYLY (SEQ ID^ NO: 4); Light chain CDR2 (L-CDR2) comprising an amino acid sequence at least 80%, 85%, 90%, 95%, or 100% identical to the amino acid sequenceRMSNLAS (SEQ ID NO: 5); and Light chain CDR3 (L-CDR3) comprising an amino acid sequence at least 80%, 85%, 90%, 95%, or 100% identical to the amino acid sequenceMQHLEYPLT (SEQ ID NO: 6).^ 2. The anti-human BTN5 (ERMAP) antibody, or fragment thereof, of claim 1, comprising: an H-CDR1 comprising the amino acid sequence of SEQ ID NO:1; an H-CDR2 comprising the amino acid sequence of SEQ ID NO:2; ^ an H-CDR3 comprising the amino acid sequence of SEQ ID NO:3; an L-CDR1 comprising the amino acid sequence of SEQ ID NO:4; an L-CDR2 comprising the amino acid sequence of SEQ ID NO:5; and an L-CDR3 comprising the amino acid sequence of SEQ ID NO:6. ^ 3. The anti-human BTN5 (ERMAP) antibody, or fragment thereof, of claim 1 or 2, comprising: 33^ ^ (a) a heavy chain comprising an amino acid sequence at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO 7; and/or (b) a light chain comprising an amino acid sequence at least 60%, 65%, 70%,^ 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:8. 4. The anti-human BTN5 (ERMAP) antibody, or fragment thereof, of claim 1 or 2, comprising: ^ (a) a heavy chain comprising an amino acid sequence at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO 7; and (b) a light chain comprising an amino acid sequence at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical^ to the amino acid sequence of SEQ ID NO:8. 5. An isolated anti-human TAPBPL antibody, or fragment thereof, comprising 1, 2, 3, 4, 5, or all 6 complementarity determining regions (CDRs) selected from the group consisting of: ^ Heavy chain CDR1 (H-CDR1) comprising an amino acid sequence at least 80%, 85%, 90%, 95%, or 100% identical to the amino acid sequence NYWIE (SEQ ID NO:9); Heavy chain CDR2 (H-CDR2) comprising an amino acid sequence at least 80%, 85%, 90%, 95%, or 100% identical to the amino acid sequenceEILPGSGSTNYNEKFKG (SEQ ID NO:10); ^ Heavy chain CDR3 (H-CDR3) comprising an amino acid sequence at least 80%, 85%, 90%, 95%, or 100% identical to the amino acid sequence FTMARYWYFDV (SEQ ID NO:11); Light chain CDR1 (L-CDR1) comprising an amino acid sequence at least 80%, 85%, 90%, 95%, or 100% identical to the amino acid sequenceRSSTGAVTTSNYAN (SEQ ID^ NO:12); Light chain CDR2 (L-CDR2) comprising an amino acid sequence at least 80%, 85%, 90%, 95%, or 100% identical to the amino acid sequenceGTSNRAP (SEQ ID NO:13); and 34^ ^ Light chain CDR3 (L-CDR3) comprising an amino acid sequence at least 80%, 85%, 90%, 95%, or 100% identical to the amino acid sequenceALWYSTH(F/Y)V (SEQ ID NO:14),; wherein residues in parentheses are options at that position. ^ 6. The anti-human TAPBPL antibody, or fragment thereof, of claim 5, comprising: an H-CDR1 comprising the amino acid sequence of SEQ ID NO:9; an H-CDR2 comprising the amino acid sequence of SEQ ID NO:10; an H-CDR3 comprising the amino acid sequence of SEQ ID NO:11; ^ an L-CDR1 comprising the amino acid sequence of SEQ ID NO:12; an L-CDR2 comprising the amino acid sequence of SEQ ID NO:13; and an L-CDR3 comprising the amino acid sequence of SEQ ID NO:14. 7. The anti-human TAPBPL antibody, or fragment thereof, of claim 5 or 6, wherein the^ L-CDR3 comprises the amino acid sequence ALWYSTHFV (SEQ ID NO:15). 8. The anti-human TAPBPL antibody, or fragment thereof, of any one of claims 5-7, comprising: (a) a heavy chain comprising an amino acid sequence at least 60%, 65%, 70%,^ 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:16; and/or (b) a light chain comprising an amino acid sequence at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 17. ^ 9. The anti-human TAPBPL antibody, or fragment thereof, of any one of claims 5-7, comprising: (a) a heavy chain comprising an amino acid sequence at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical^ to the amino acid sequence of SEQ ID NO:16; and (b) a light chain comprising an amino acid sequence at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 17. 35^ ^
10. An isolated anti-human TAPBPL antibody, or fragment thereof, comprising 1, 2, 3, 4, 5, or all 6 complementarity determining regions (CDRs) selected from the group consisting of: ^ Heavy chain CDR1 (H-CDR1) comprising an amino acid sequence at least 80%, 85%, 90%, 95%, or 100% identical to the amino acid sequence RYWMS (SEQ ID NO:18); Heavy chain CDR2 (H-CDR2) comprising an amino acid sequence at least 80%, 85%, 90%, 95%, or 100% identical to the amino acid sequenceEINPDSSTINYTPSLKD (SEQ ID NO:19); ^ Heavy chain CDR3 (H-CDR3) comprising an amino acid sequence at least 80%, 85%, 90%, 95%, or 100% identical to the amino acid sequence VTTVVARDWYFDV (SEQ ID NO:20); Light chain CDR1 (L-CDR1) comprising an amino acid sequence at least 80%, 85%, 90%, 95%, or 100% identical to the amino acid sequence of SEQ ID NO:12; ^ Light chain CDR2 (L-CDR2) comprising an amino acid sequence at least 80%, 85%, 90%, 95%, or 100% identical to the amino acid sequence of SEQ ID NO:13; and Light chain CDR3 (L-CDR3) comprising an amino acid sequence at least 80%, 85%, 90%, 95%, or 100% identical to the amino acid sequence of SEQ ID NO:14. ^ 11. The anti-human TAPBPL antibody, or fragment thereof, of claim 10, comprising: an H-CDR1 comprising the amino acid sequence of SEQ ID NO:18; an H-CDR2 comprising the amino acid sequence of SEQ ID NO:19; an H-CDR3 comprising the amino acid sequence of SEQ ID NO:20; an L-CDR1 comprising the amino acid sequence of SEQ ID NO:12; ^ an L-CDR2 comprising the amino acid sequence of SEQ ID NO:13; and an L-CDR3 comprising the amino acid sequence of SEQ ID NO:14. 12. The anti-human TAPBPL antibody, or fragment thereof, of claim 10 or 11, wherein the L-CDR3 comprises the amino acid sequenceALWYSTHYV (SEQ ID NO:49). ^ 13. The anti-human TAPBPL antibody, or fragment thereof, of any one of claims 10-12, comprising: 36^ ^ (a) a heavy chain comprising an amino acid sequence at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:21; and/or (b) a light chain comprising an amino acid sequence at least 60%, 65%, 70%,^ 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:22. 14. The anti-human TAPBPL antibody, or fragment thereof, of any one of claims 10-12, comprising: ^ (a) a heavy chain comprising an amino acid sequence at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:21; and (b) a light chain comprising an amino acid sequence at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical^ to the amino acid sequence of SEQ ID NO:22. 15. An isolated anti-human CD300c antibody, or fragment thereof, comprising 1, 2, 3, 4, 5, or all 6 complementarity determining regions (CDs) selected from the group consisting of: Heavy chain CDR1 (H-CDR1) comprising an amino acid sequence at least 80%,^ 85%, 90%, 95%, or 100% identical to the amino acid sequenceGYNMN (SEQ ID NO:23); Heavy chain CDR2 (H-CDR2) comprising an amino acid sequence at least 80%, 85%, 90%, 95%, or 100% identical to the amino acid sequenceNIDPYYGGTSYNQKFKG (SEQ ID NO:24); Heavy chain CDR3 (H-CDR3) comprising an amino acid sequence at least 80%,^ 85%, 90%, 95%, or 100% identical to the amino acid sequenceSGYYYAMDY (SEQ ID NO:25); Light chain CDR1 (L-CDR1) comprising an amino acid sequence at least 80%, 85%, 90%, 95%, or 100% identical to the amino acid sequenceKASQNVGTAVA (SEQ ID NO:26); Light chain CDR2 (L-CDR2) comprising an amino acid sequence at least 80%, 85%,^ 90%, 95%, or 100% identical to the amino acid sequenceSASNRYT (SEQ ID NO:27); and Light chain CDR3 (L-CDR3) comprising an amino acid sequence at least 80%, 85%, 90%, 95%, or 100% identical to the amino acid sequenceQQYSSYPYT (SEQ ID NO:28). 37^ ^
16. The anti-human CD300c antibody, or fragment thereof, of claim 15, comprising: an H-CDR1 comprising the amino acid sequence of SEQ ID NO:23; an H-CDR2 comprising the amino acid sequence of SEQ ID NO:24; an H-CDR3 comprising the amino acid sequence of SEQ ID NO:25; ^ an L-CDR1 comprising the amino acid sequence of SEQ ID NO:26; an L-CDR2 comprising the amino acid sequence of SEQ ID NO:27; and an L-CDR3 comprising the amino acid sequence of SEQ ID NO:28. 17. The anti-human CD300c antibody, or fragment thereof, of claim 15 or 16, comprising^ (a) a heavy chain comprising an amino acid sequence at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:29; and/or (b) a light chain comprising an amino acid sequence at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical^ to the amino acid sequence of SEQ ID NO:30). 18. The anti-human CD300c antibody, or fragment thereof, of claim 15 or 16, comprising (a) a heavy chain comprising an amino acid sequence at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical^ to the amino acid sequence of SEQ ID NO:29; and (b) a light chain comprising an amino acid sequence at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:30. ^ 19. An isolated anti-human CD300c antibody, or fragment thereof, comprising 1, 2, 3, 4, 5, or all 6 complementarity determining regions (CDs) selected from the group consisting of: Heavy chain CDR1 (H-CDR1) comprising an amino acid sequence at least 80%, 85%, 90%, 95%, or 100% identical to the amino acid sequenceDYYMK (SEQ ID NO:31); Heavy chain CDR2 (H-CDR2) comprising an amino acid sequence at least 80%,^ 85%, 90%, 95%, or 100% identical to the amino acid sequenceDINPNNGDTFYNQKFKG (SEQ ID NO:32); 38^ ^ Heavy chain CDR3 (H-CDR3) comprising an amino acid sequence at least 80%, 85%, 90%, 95%, or 100% identical to the amino acid sequenceGGMVTTAMDY (SEQ ID NO:33); Light chain CDR1 (L-CDR1) comprising an amino acid sequence at least 80%, 85%,^ 90%, 95%, or 100% identical to the amino acid sequenceRTITDIDDDMN (SEQ ID NO:34); Light chain CDR2 (L-CDR2) comprising an amino acid sequence at least 80%, 85%, 90%, 95%, or 100% identical to the amino acid sequenceEGNTLRP (SEQ ID NO:35); and Light chain CDR3 (L-CDR3) comprising an amino acid sequence at least 80%, 85%, 90%, 95%, or 100% identical to the amino acid sequenceLQSDNMPYT (SEQ ID NO:36).^ 20. The anti-human CD300c antibody, or fragment thereof, of claim 19, comprising: an H-CDR1 comprising the amino acid sequence of SEQ ID NO:31; an H-CDR2 comprising the amino acid sequence of SEQ ID NO:32; an H-CDR3 comprising the amino acid sequence of SEQ ID NO:33; ^ an L-CDR1 comprising the amino acid sequence of SEQ ID NO:34; an L-CDR2 comprising the amino acid sequence of SEQ ID NO:35; and an L-CDR3 comprising the amino acid sequence of SEQ ID NO:36. 21. The anti-human CD300c antibody, or fragment thereof, of claim 19 or 20, ^ comprising: (a) a heavy chain comprising an amino acid sequence at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:37; and/or (b) a light chain comprising an amino acid sequence at least 60%, 65%, 70%,^ 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:38. 22. The anti-human CD300c antibody, or fragment thereof, of claim 19 or 20, comprising: ^ (a) a heavy chain comprising an amino acid sequence at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:37; and 39^ ^ (b) a light chain comprising an amino acid sequence at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:38. ^ 23. An isolated anti-human CD300c antibody, or fragment thereof, comprising 1, 2, 3, 4, 5, or all 6 complementarity determining regions (CDs) selected from the group consisting of: Heavy chain CDR1 (H-CDR1) comprising an amino acid sequence at least 80%, 85%, 90%, 95%, or 100% identical to the amino acid sequenceDYYMY (SEQ ID NO:39); Heavy chain CDR2 (H-CDR2) comprising an amino acid sequence at least 80%,^ 85%, 90%, 95%, or 100% identical to the amino acid sequenceTISNGGSYTYYPDSVKG (SEQ ID NO:40); Heavy chain CDR3 (H-CDR3) comprising an amino acid sequence at least 80%, 85%, 90%, 95%, or 100% identical to the amino acid sequenceGGDYYGNTYAY (SEQ ID NO:41); ^ Light chain CDR1 (L-CDR1) comprising an amino acid sequence at least 80%, 85%, 90%, 95%, or 100% identical to the amino acid sequenceKASQSVDYDGDSYIN (SEQ ID NO:42); Light chain CDR2 (L-CDR2) comprising an amino acid sequence at least 80%, 85%, 90%, 95%, or 100% identical to the amino acid sequenceAASNLES (SEQ ID NO:43); and^ Light chain CDR3 (L-CDR3) comprising an amino acid sequence at least 80%, 85%, 90%, 95%, or 100% identical to the amino acid sequenceQQSNEDPYT (SEQ ID NO:44). 24. The anti-human CD300c antibody, or fragment thereof, of claim 23, comprising: an H-CDR1 comprising the amino acid sequence of SEQ ID NO:39; ^ an H-CDR2 comprising the amino acid sequence of SEQ ID NO:40; an H-CDR3 comprising the amino acid sequence of SEQ ID NO:41; an L-CDR1 comprising the amino acid sequence of SEQ ID NO:42; an L-CDR2 comprising the amino acid sequence of SEQ ID NO:43; and an L-CDR3 comprising the amino acid sequence of SEQ ID NO:44. ^ 25. The anti-human CD300c antibody, or fragment thereof, of claim 23 or 24, comprising: 40^ ^ (a) a heavy chain comprising an amino acid sequence at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:45; and/or (b) a light chain comprising an amino acid sequence at least 60%, 65%, 70%,^ 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:46. 26. The anti-human CD300c antibody, or fragment thereof, of claim 23 or 24, comprising: ^ (a) a heavy chain comprising an amino acid sequence at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:45; and (b) a light chain comprising an amino acid sequence at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical^ to the amino acid sequence of SEQ ID NO:46. 27. The antibody or fragment thereof of any preceding claim, wherein the antibody comprises a monoclonal antibody, or fragment thereof. ^ 28. The antibody or fragment thereof of any preceding claim, wherein the antibody comprises a humanized antibody, or fragment thereof. 29. The antibody or fragment thereof of any preceding claim, wherein the antibody is a chimeric antibody. ^ 30. The antibody or fragment thereof of claim 29, wherein the heavy chain of any embodiment disclosed herein may further comprise an amino acid sequence at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence selected from SEQ ID NO:47 and 70-72. ^ 31. The antibody or fragment thereof of claim 29, wherein the light chain of any embodiment disclosed herein may further comprise an amino acid sequence at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence selected from SEQ ID NO:48 and 73. 41^ ^
32. The antibody or fragment thereof of any preceding claim, wherein the heavy chain or light chain comprises an amino acid sequence at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino^ acid sequence selected from SEQ ID NO:50-61. 33. The antibody or fragment thereof of any preceding claim, comprising a heavy chain and a light chain comprising an amino acid sequence at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the^ amino acid sequence of a heavy chain-light chain pair selected from the group consisting of: SEQ ID NO:50-51; SEQ ID NO:52-53; SEQ ID NO:54-55; SEQ ID NO:56-57; ^ SEQ ID NO:58-59; and SEQ ID NO:60-61. 34. The antibody or fragment thereof of any preceding claim, further comprising a therapeutic agent, including but not limited to a chemotherapeutic, conjugated to the antibody^ or fragment thereof. 35. A nucleic acid encoding the antibody or fragment thereof of any preceding claim. 36. A vector comprising the nucleic acid of claim 35 operatively linked to a suitable^ control sequence, such as a promoter. 37. A host cell comprising the antibody or fragment thereof, the nucleic acid and/or the expression vector of any preceding claim. ^ 38. A pharmaceutical composition, comprising (a) the antibody or fragment thereof, the nucleic acid, the vector, and/or the host cell of any preceding claim; and (b) a pharmaceutically acceptable carrier. 42^ ^
39. A method for treating cancer, comprising administering to a subject in need thereof the antibody or fragment thereof, the nucleic acid, the vector, the host cell, and/or the pharmaceutical composition of any preceding claim, in an amount effective to treat the cancer. ^ 40. The method of claim 37 wherein the cancer is selected from the group consisting of breast cancer, lung cancer, colon cancer, melanoma, prostate cancer, leukemia, neuroblastoma, liver, lymphoma, cervical cancer, ovarian cancer, gastric cancer, and esophageal cancer. ^ 43^ ^
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