Antigen-binding proteins recognizing peptides from MAGE-A4

文档序号:1549136 发布日期:2020-01-17 浏览:21次 中文

阅读说明:本技术 识别来自mage-a4的肽的抗原结合性蛋白 (Antigen-binding proteins recognizing peptides from MAGE-A4 ) 是由 珠玖洋 赤堀泰 加藤裕也 宫原庆裕 于 2018-06-05 设计创作,主要内容包括:本发明所要解决的技术问题在于:提供一种能够用于使用癌症特异性细胞内抗原的CAR输注疗法的CAR-T细胞。解决技术问题的技术方案为:通过如下的癌症治疗用CAR-T细胞来解决,该癌症治疗用CAR-T细胞具有识别来自MAGE-A4的肽和HLA-A2复合体的抗体,上述抗体具有序列号36的VH的氨基酸序列和序列号38的VL的氨基酸序列。此时,上述抗体优选具有序列号32的氨基酸序列。(The technical problem to be solved by the invention is as follows: a CAR-T cell is provided that can be used for CAR infusion therapy with a cancer-specific intracellular antigen. The technical scheme for solving the technical problem is as follows: the problem is solved by a CAR-T cell for cancer therapy, which has an antibody that recognizes a peptide derived from MAGE-A4 and an HLA-A2 complex, and the antibody has the amino acid sequence of VH of SEQ ID NO. 36 and the amino acid sequence of VL of SEQ ID NO. 38. In this case, the antibody preferably has the amino acid sequence of SEQ ID NO. 32.)

1. An antigen binding protein, characterized by:

recognizing the HLA-A2-MAGE-A4 complex as an antigen, the antigen-binding protein comprising a polypeptide of (A) or (B) below:

(A) a polypeptide comprising the amino acid sequence of VH (heavy chain variable region) of seq id No. 36 and the amino acid sequence of VL (light chain variable region) of seq id No. 38;

(B) a polypeptide comprising an amino acid sequence having 90% or more homology with the amino acid sequence of VH (heavy chain variable region) of sequence No. 36 and an amino acid sequence having 90% or more homology with the amino acid sequence of VL (light chain variable region) of sequence No. 38.

2. The antigen binding protein of claim 1, wherein:

a polypeptide comprising the following (C) or (D) between VH and VL:

(C) a polypeptide comprising an amino acid sequence of sc (single chain) of SEQ ID NO. 37;

(D) a polypeptide comprising an amino acid sequence having a homology of 90% or more with the sc (single-chain) amino acid sequence of SEQ ID NO. 37.

3. The antigen binding protein of claim 1 or 2, wherein:

it is a polypeptide comprising the amino acid sequence of SEQ ID NO. 32 or an amino acid sequence having 90% or more homology with the amino acid sequence of SEQ ID NO. 32.

4. The antigen binding protein of any one of claims 1 to 3, wherein:

the antigen-binding protein is Fab, Fab ', F (ab')2Fv or single chain Fv (scFv).

5. A nucleic acid encoding the antigen binding protein of any one of claims 1 to 4.

6. A carrier, characterized by:

comprising the nucleic acid of claim 5.

7. A chimeric antigen receptor characterized by:

an intracellular domain comprising the antigen binding protein of any one of claims 1 to 4 and a signaling protein.

8. The chimeric antigen receptor according to claim 7, wherein:

the signaling protein is any of the CD3zeta (CD3 zeta) chain or the costimulatory molecule CD (GITR).

9. The chimeric antigen receptor according to claim 8, wherein:

also included are any of the intracellular domains of CD28 or GITR.

10. A nucleic acid encoding the chimeric antigen receptor of any one of claims 7 to 9.

11. A carrier, characterized by:

comprising the nucleic acid of claim 10.

12. A cell expressing the chimeric antigen receptor of any one of claims 7 to 9.

13. A pharmaceutical composition, comprising:

comprising the cell according to claim 12 as an active ingredient.

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