JPWO2019165156A5 - - Google Patents

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JPWO2019165156A5
JPWO2019165156A5 JP2020543928A JP2020543928A JPWO2019165156A5 JP WO2019165156 A5 JPWO2019165156 A5 JP WO2019165156A5 JP 2020543928 A JP2020543928 A JP 2020543928A JP 2020543928 A JP2020543928 A JP 2020543928A JP WO2019165156 A5 JPWO2019165156 A5 JP WO2019165156A5
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cells
domain
acid sequence
amino acid
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JP2021513857A (en
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ＣＤ８３抗原結合ドメインと、膜貫通ドメインと、細胞内シグナル伝達ドメインと、同時刺激シグナル伝達領域と、を含む、キメラ抗原受容体（ＣＡＲ）ポリペプチド。 A chimeric antigen receptor (CAR) polypeptide comprising a CD83 antigen binding domain, a transmembrane domain, an intracellular signaling domain, and a co-stimulation signaling region. 前記ＣＤ８３抗原結合ドメインが、ＣＤ８３に特異的に結合する抗体の１本鎖可変断片（ｓｃＦｖ）である、請求項１に記載のポリペプチド。 The polypeptide according to claim 1, wherein the CD83 antigen-binding domain is a single-chain variable fragment (scFv) of an antibody that specifically binds to CD83. 抗ＣＤ８３ｓｃＦｖが、ＣＤＲ１、ＣＤＲ２及びＣＤＲ３配列を有する可変重鎖（ＶＨ）ドメインと、ＣＤＲ１、ＣＤＲ２及びＣＤＲ３配列を有する可変軽鎖（ＶＬ）ドメインと、を含み、前記ＶＨドメインのＣＤＲ１配列が、アミノ酸配列の配列番号１、配列番号７又は配列番号１３を含み；前記ＶＨドメインのＣＤＲ２配列が、アミノ酸配列の配列番号２、配列番号８又は配列番号１４を含み；前記ＶＨドメインのＣＤＲ３配列が、アミノ酸配列の配列番号３、配列番号９又は配列番号１５を含み；前記ＶＬのＣＤＲ１配列が、アミノ酸配列の配列番号４、配列番号１０又は配列番号１６を含み；前記ＶＬドメインのＣＤＲ２配列が、アミノ酸配列の配列番号５、配列番号１１又は配列番号１７を含み；前記ＶＬドメインのＣＤＲ３配列が、アミノ酸配列の配列番号６、配列番号１２又は配列番号１８を含む、請求項２に記載のポリペプチド。 The anti-CD83scFv comprises a variable heavy chain ( VH ) domain having CDR1, CDR2 and CDR3 sequences and a variable light chain ( VL ) domain having CDR1, CDR2 and CDR3 sequences, the CDR1 sequence of said VH domain. Includes SEQ ID NO: 1, SEQ ID NO: 7 or SEQ ID NO: 13 of the amino acid sequence; the CDR2 sequence of the VH domain comprises SEQ ID NO: 2, SEQ ID NO: 8 or SEQ ID NO: 14 of the amino acid sequence; The CDR3 sequence comprises SEQ ID NO: 3, SEQ ID NO: 9 or SEQ ID NO: 15 of the amino acid sequence; the CDR1 sequence of the VL comprises SEQ ID NO: 4, SEQ ID NO: 10 or SEQ ID NO: 16 of the amino acid sequence; said VL domain. The CDR2 sequence of the above contains SEQ ID NO: 5, SEQ ID NO: 11 or SEQ ID NO: 17 of the amino acid sequence; the CDR3 sequence of the VL domain comprises SEQ ID NO: 6, SEQ ID NO: 12 or SEQ ID NO: 18 of the amino acid sequence. 2. The polypeptide according to 2. 前記抗ＣＤ８３ｓｃＦｖのＶＨドメインが、アミノ酸配列の配列番号１９、配列番号４８、配列番号４９、配列番号５０、配列番号５１、配列番号５２又は配列番号５３を含む、請求項３に記載のポリペプチド。 The polypeptide according to claim 3, wherein the VH domain of the anti-CD83scFv comprises the amino acid sequence SEQ ID NO: 19, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52 or SEQ ID NO: 53. .. 前記抗ＣＤ８３ｓｃＦｖのＶＬドメインが、アミノ酸配列の配列番号２０、配列番号５４又は配列番号５５を含む、請求項３又は４に記載のポリペプチド。 The polypeptide according to claim 3 or 4, wherein the VL domain of the anti-CD83scFv comprises the amino acid sequence SEQ ID NO: 20, SEQ ID NO: 54 or SEQ ID NO: 55. 前記抗ＣＤ８３ｓｃＦｖが、アミノ酸配列の配列番号５７、配列番号５８、配列番号５９、配列番号６０、配列番号６１、配列番号６２、配列番号６３、配列番号６４、配列番号６５、配列番号６６、配列番号６７、配列番号６８、配列番号６９、配列番号７０又は配列番号７１を含む、請求項１～５の何れか１項に記載のポリペプチド。 The anti-CD83scFv is the amino acid sequence SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, the polypeptide of any one of claims 1-5, comprising SEQ ID NO: 68, SEQ ID NO: 69, SEQ ID NO: 70 or SEQ ID NO: 71. 前記同時刺激シグナル伝達領域が、ＣＤ２７、ＣＤ２８、４－１ＢＢ、ＯＸ４０、ＣＤ３０、ＣＤ４０、ＰＤ－１、ＩＣＯＳ、リンパ球機能関連抗原－１（ＬＦＡ－１）、ＣＤ２、ＣＤ７、ＬＩＧＨＴ、ＮＫＧ２Ｃ、Ｂ７－Ｈ３及び何らかのそれらの組み合わせからなる群から選択される同時刺激分子の細胞質ドメインを含む、請求項１～６の何れか１項に記載のポリペプチド。 The simultaneous stimulation signal transduction region is CD27, CD28, 4-1BB, OX40, CD30, CD40, PD-1, ICOS, lymphocyte function-related antigen-1 (LFA-1), CD2, CD7, LIGHT, NKG2C, B7. The polypeptide according to any one of claims 1 to 6, comprising the cytoplasmic domain of a co-stimulatory molecule selected from the group consisting of H3 and any combination thereof. 前記ＣＡＲポリペプチドが、式：
ＳＰ－ＣＤ８３－ＨＧ－ＴＭ－ＣＳＲ－ＩＳＤ；又は
ＳＰ－ＣＤ８３－ＨＧ－ＴＭ－ＩＳＤ－ＣＳＲ
により定義され、
式中、「ＳＰ」がシグナルペプチドを表し、
式中、「ＣＤ８３」がＣＤ８３結合領域を表し、
式中、「ＨＧ」が任意選択のヒンジドメインを表し、
式中、「ＴＭ」が膜貫通ドメインを表し、
式中、「ＣＳＲ」が同時刺激シグナル伝達領域を表し、
式中、「ＩＳＤ」が細胞内シグナル伝達ドメインを表し、
式中、「－」が二価リンカーを表す、
請求項１～７の何れか１項に記載のポリペプチド。 The CAR polypeptide has the formula:
SP-CD83-HG-TM-CSR-ISD; or SP-CD83-HG-TM-ISD-CSR
Defined by
In the formula, "SP" represents the signal peptide,
In the formula, "CD83" represents the CD83 binding region.
In the formula, "HG" represents an optional hinge domain,
In the formula, "TM" represents the transmembrane domain,
In the formula, "CSR" represents the simultaneous stimulation signal transduction region,
In the formula, "ISD" represents the intracellular signal transduction domain,
In the formula, "-" represents a divalent linker,
The polypeptide according to any one of claims 1 to 7. 前記細胞内シグナル伝達ドメインが、ＣＤ３ゼータ（ＣＤ３ζ）シグナル伝達ドメインを含む、請求項１～８の何れか１項に記載のポリペプチド。 The polypeptide according to any one of claims 1 to 8, wherein the intracellular signal transduction domain comprises a CD3 zeta (CD3ζ) signal transduction domain. 請求項１～９の何れか１項に記載の組み換えポリペプチドをコードする、単離核酸配列。 An isolated nucleic acid sequence encoding the recombinant polypeptide according to any one of claims 1 to 9. 請求項１０に記載の単離核酸配列を含む、ベクター。 A vector comprising the isolated nucleic acid sequence of claim 10. 請求項１１に記載のベクターを含む、細胞。 A cell comprising the vector according to claim 11. αβＴ細胞、γδＴ細胞、ナチュラルキラー（ＮＫ）細胞、ナチュラルキラーＴ（ＮＫＴ）細胞、Ｂ細胞、自然リンパ系細胞（ＩＬＣ）、サイトカイン誘導性キラー（ＣＩＫ）細胞、細胞傷害性Ｔリンパ球（ＣＴＬ）、リンホカイン活性化キラー（ＬＡＫ）細胞、制御Ｔ細胞又は何らかのそれらの組み合わせからなる群から選択される、請求項１２に記載の細胞。 αβT cells, γδT cells, natural killer (NK) cells, natural killer T (NKT) cells, B cells, natural lymphoid cells (ILC), cytokine-induced killer (CIK) cells, cytotoxic T lymphocytes (CTL) The cell according to claim 12, which is selected from the group consisting of lymphokine-activated killer (LAK) cells, regulatory T cells, or some combination thereof. 前記ＣＡＲの抗原結合ドメインがＣＤ８３に結合するとき、アロ反応性ドナー細胞を抑制する、請求項１３に記載の細胞。 13. The cell of claim 13, which suppresses alloreactive donor cells when the antigen-binding domain of CAR binds to CD83. 移植ドナー細胞を受けた対象においてアロ反応性ドナー細胞を抑制するための医薬組成物であって、請求項１～９の何れか１項に記載のＣＡＲポリペプチドを発現するように遺伝子改変された免疫エフェクター細胞を含み、
前記医薬組成物が有効量で前記対象に投与され、それによって前記対象においてアロ反応性ドナー細胞を抑制する、医薬組成物。 A pharmaceutical composition for suppressing alloreactive donor cells in a subject receiving a transplanted donor cell, which has been genetically modified to express the CAR polypeptide according to any one of claims 1 to 9. Contains immune effector cells ,
A pharmaceutical composition, wherein the pharmaceutical composition is administered to the subject in an effective amount , thereby suppressing alloreactive donor cells in the subject. 前記免疫エフェクター細胞が、Ｔ細胞、ナチュラルキラー（ＮＫ）細胞、細胞傷害性Ｔリンパ球（ＣＴＬ）及び制御Ｔ細胞からなる群から選択される、請求項１５に記載の医薬組成物。 The pharmaceutical composition according to claim 15, wherein the immune effector cells are selected from the group consisting of T cells, natural killer (NK) cells, cytotoxic T lymphocytes (CTL) and regulatory T cells. 前記ドナー細胞が、アロ反応性Ｔ細胞、樹状細胞又はそれらの組み合わせを含む骨髄細胞である、請求項１５又は１６に記載の医薬組成物。 The pharmaceutical composition according to claim 15 or 16, wherein the donor cell is a bone marrow cell containing allo-reactive T cells, dendritic cells or a combination thereof . 前記医薬組成物がさらにチェックポイント阻害剤を含み、前記チェックポイント阻害剤が、抗ＰＤ－１抗体、抗ＰＤ－Ｌ１抗体、抗ＣＴＬＡ－４抗体又はそれらの組み合わせを含む、請求項１７に記載の医薬組成物。
17. The pharmaceutical composition further comprises a checkpoint inhibitor, wherein the checkpoint inhibitor comprises an anti-PD-1 antibody, an anti-PD-L1 antibody, an anti-CTLA-4 antibody or a combination thereof. Pharmaceutical composition .
JP2020543928A 2018-02-23 2019-02-22 CD83-binding chimeric antigen receptor Active JP7358369B2 (en)

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US201862634435P 2018-02-23 2018-02-23
US62/634,435 2018-02-23
US201862677783P 2018-05-30 2018-05-30
US62/677,783 2018-05-30
PCT/US2019/019065 WO2019165156A1 (en) 2018-02-23 2019-02-22 Cd83-binding chimeric antigen receptors

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AU (1) AU2019226101A1 (en)
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CN114929341A (en) * 2019-08-16 2022-08-19 H.李.莫菲特癌症中心和研究所股份有限公司 Chimeric antigen receptor for the treatment of myeloid malignancies
US11802159B2 (en) * 2019-09-30 2023-10-31 The Trustees Of The University Of Pennsylvania Humanized anti-GDNF family alpha-receptor 4 (GRF-alpha-4) antibodies and chimeric antigen receptors (CARs)
WO2021127212A2 (en) * 2019-12-18 2021-06-24 H. Lee Moffitt Cancer Center And Research Institute Inc. Systems and methods for producing efficacious regulatory t cells
US20230390391A1 (en) * 2020-01-22 2023-12-07 Regents Of The University Of Minnesota Bi-specific chimeric antigen receptor t cells targeting cd83 and interleukin 6 receptor
US20230107770A1 (en) * 2020-02-20 2023-04-06 H. Lee Moffitt Cancer Center And Research Institute, Inc. Method of enhancing immunotherapy using er stress pathway inhibitors
US20230321239A1 (en) * 2020-08-14 2023-10-12 H. Lee Moffitt Cancer Center And Research Institute Inc. Chimeric antigen receptor t cells for treating autoimmunity

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