Chimeric antigen receptor that binds HLA-DR and CAR-T cell
The present invention relates to an antigen-binding molecule comprising a heavy chain variable region comprising a heavy-chain complementarity-determining region 1 (HCDR1) comprising an amino acid sequence represented by Sequence No. 1, an HCDR2 comprising an amino acid sequence represented by Sequence No. 2, and an HCDR3 comprising an amino acid sequence represented by Sequence No. 3; a light-chain variable region comprising a light-chain complementarity-determining region 1 (LCDR1) comprising an amino acid sequence represented by Sequence No. 4, an LCDR2 comprising an amino acid sequence represented by Sequence No. 5, and an LCDR3 comprising an amino acid sequence represented by Sequence No. 6; wherein the antigen-binding molecule is a T cell receptor (TCR); and to a cell line expressing the same.
1. An antigen binding molecule, comprising, a heavy-chain variable region of SEQ ID NO: 7 and a light-chain variable region of SEQ ID NO: 8, wherein the antigen-binding molecule is a chimeric antigen receptor (CAR).
2. An antigen binding molecule according to claim 1 , comprising the amino acid sequence represented by SEQ ID NO: 9.
3. An antigen binding molecule according to claim 1 , further comprising the amino acid sequence represented by SEQ ID NO: 13.
4. An antigen binding molecule according to claim 1 , further comprising an amino acid sequence represented by SEQ ID NO: 14.
5. An antigen binding molecule according to claim 1 , further comprising a transmembrane domain and an intracellular signaling domain for activating T cells.
6. An antigen binding molecule according to claim 5 , in which the said transmembrane domain is selected from the group: of an alpha chain of a T cell receptor, a beta chain of a T cell receptor, a zeta chain of a T cell receptor, CD28, CD45, CD4, CD5, CD8, CD9, CD16, CD22, CD33, CD37, CD64, CD80, CD86, CD134, CD137 and CD154, wherein the said intracellular signaling domain is a CD3zeta signaling domain and a co-stimulatory signaling domain.
7. An antigen binding molecule according to claim 6 , wherein the co-stimulatory signaling domain is selected from the group of CD28, OXO40, CD27, ICAM-1, CD278, and CD137.
8. A method of treating cancer, comprising a step of administering, to a patient having cancer, a pharmaceutical composition comprising a T cell comprising a therapeutically effective quantity of the antigen-binding molecule of claim 1 .
9. The method of claim 8 , wherein the pharmaceutical composition comprises CD8+ T cells, or CD4+ T cells and CD8+ T cells.
10. The method of claim 9 , wherein the pharmaceutical composition comprises CD4+ T cells and CD8+ T cells.
11. The method of claim 10 , wherein the proportion of cell counts of CD4+ T cells to CD8+ T cells is substantially 1:1.
12. A therapeutic pharmaceutical composition for treating cancer, comprising as a pharmaceutically effective ingredient, T cells comprising the antigen-binding molecule of claim 1 .
13. A therapeutic pharmaceutical composition of claim 1 in which the pharmaceutical composition either comprises CD8+ T cells or comprises CD4+ T cells and CD8+ T cells.
14. The therapeutic pharmaceutical composition of claim 13 , wherein the pharmaceutical composition comprises CD4+ T cells and CD8+ T cells.
15. The therapeutic pharmaceutical composition of claim 14 , in which the proportion of cell counts of CD4+ T cells to CD8+ T cells is substantially 1:1.