JPWO2021158534A5

JPWO2021158534A5 -

Info

Publication number: JPWO2021158534A5
Application number: JP2022547671A
Authority: JP
Publication date: 2024-02-09

Claims

A method of inducing expansion and proliferation of chimeric antigen receptor (CAR) T cells, the method comprising:
A method comprising incubating a CAR T cell with a hapten antigen presenting cell (H-APC), the CAR T cell comprising a CAR that specifically binds to a hapten bound to the H-APC.

2. The method of claim 1, wherein the CAR T cells and the H-APCs are derived from a single subject.

2. The method of claim 1, wherein the CAR T cell comprises a CAR that specifically binds a tumor-specific antigen.

A pharmaceutical composition for treating, suppressing or alleviating cancer in a subject, the composition comprising:
Contains hapten-containing hapten antigen presenting cells (H-APCs),
the subject comprises chimeric antigen receptor (CAR) T cells;
The CAR of the CAR T cell specifically binds to a tumor-specific antigen of the cancer, the CAR of the CAR T cell specifically binds to the hapten,
A pharmaceutical composition, wherein administration of said H-APC induces expansion of said CAR T cells.

5. The pharmaceutical composition of claim 4, wherein the CAR T cells and the H-APC are derived from the subject.

6. The method of any one of claims 1-3, or the pharmaceutical composition of claim 4 or 5, wherein the CAR T cells comprise a bispecific CAR.

The method according to any one of claims 1 to 3, or the pharmaceutical composition according to claims 4 or 5, wherein the CAR T cells contain two or more CARs.

Any of claims 1 to 3, wherein the CAR T cell comprises a first ligand-binding domain that specifically binds to a tumor-specific antigen and a second ligand-binding domain that specifically binds to the hapten. 6. The method according to claim 1 or the pharmaceutical composition according to claim 4 or 5.

6. The method of any one of claims 1-3, or the pharmaceutical composition of claim 4 or 5, wherein the CAR T cells comprise a monospecific CAR.

The tumor-specific antigen is CD19, CD22, HER2, CD7, CD30, B cell maturation antigen (BCMA), GD2, glypican 3, MUC1, CD70, CD33, epithelial cell adhesion molecule (EpCAM), epidermal growth factor variant III, 4. The tyrosine kinase-like orphan receptor 1 (ROR1), CD123, prostate stem cell antigen (PSCA), CD5, Lewis Y antigen, B7H3, CD20, CD43, HSP90 and IL13. 6. A method as described or a pharmaceutical composition as claimed in claim 4 or 5.

The method according to any one of claims 1 to 3, or the pharmaceutical composition according to claims 4 or 5, wherein the hapten is selected from the haptens listed in Table 1.

the hapten is selected from fluorescein, urushiol, quinone, biotin and dinitrophenol and derivatives thereof, and/or the CAR that specifically binds to the hapten is any of SEQ ID NOs: 1-6, 8 and 10. scFv comprising an amino acid sequence having at least 95% sequence identity to one
The method according to any one of claims 1 to 3, or the pharmaceutical composition according to claims 4 or 5.

Any one of claims 1 to 3, wherein the hapten is covalently bound to the extracellular surface of the H-APC, and the hapten is optionally bound to the H-APC via an ether phospholipid (PLE). 6. The method according to claim 1 or the pharmaceutical composition according to claim 4 or 5.

The CAR T cells are derived from CD4+ cells, CD8+ cells, progenitor T cells, or hematopoietic stem cells, and the CD8+ cells are derived from naive CD8+ T cells, central memory CD8+ T cells, effector memory CD8+ T cells, and The CD8+ cytotoxic T lymphocytes may be selected from the group consisting of bulk CD8+ T cells, wherein said CD4+ cells include naive CD4+ T cells, central memory CD4+ T cells, effector memory CD4+ T cells, and The method according to any one of claims 1 to 3, or the pharmaceutical composition according to claims 4 or 5, which may be a CD4+ helper T lymphocyte selected from the group consisting of bulk CD4+ T cells. .

The method according to any one of claims 1 to 3, or the pharmaceutical composition according to claims 4 or 5, wherein the H-APC is derived from a T cell or a B cell.

A composition comprising a hapten antigen presenting cell (H-APC) comprising a hapten, and a CAR T cell comprising a first chimeric antigen receptor (CAR) and a second chimeric antigen receptor (CAR), the composition comprising:
the first CAR is capable of specifically binding to a cancer antigen;
the second CAR specifically binds to the hapten;
(i) the hapten may be selected from fluorescein, urushiol, quinone, biotin, dinitrophenol or derivatives thereof, and the second CAR is any one of SEQ ID NOs: 1-6, 8 and 10; scFv comprising an amino acid sequence having at least 95% sequence identity to
(ii) said hapten may be coupled to said H-APC via an ether phospholipid (PLE), and/or (iii) said H-APC and said CAR T cell are combined in a single subject. The composition may be derived from.