Humanized bcma antibody and bcma-car-t cells
AssigneeCaribou Biosciences, Inc.
InventorsLIJUN WU, VITA GOLUBOVSKAYA
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Abstract
The present invention is directed to a humanized BCMA single-chain variable fragment (scFv), comprising VH having the amino acid sequence of SEQ ID NO: 3 and VL having the amino acid sequence of SEQ ID NO: 5. The present invention is also directed to a BCMA chimeric antigen receptor fusion protein comprising from N-terminus to C-terminus: (i) a single-chain variable fragment (scFv) of the present invention, (ii) a transmembrane domain, (iii) at least one co-stimulatory domains, and (iv) an activating domain. This humanized BCMA-CAR-T cells have specific killing activity against BCMA-positive tumor cells.
Claims27
1-27. (canceled)
A therapeutic agent for inhibiting growth of tumors, the agent comprising immune cells expressing an anti-BCMA chimeric antigen receptor (CAR) having an anti-BCMA single-chain variable fragment (scFv) comprising:
- a. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO:
- 3, and a light chain variable region VL) comprising the amino acid sequence of SEQ ID NO:
- 5;
- b. a transmembrane domain;
- c. a co-stimulatory domain;
- and
- d. an activating domain;
- and further comprising an excipient.
The therapeutic agent of claim 1, wherein the immune cells are selected from T cells, NK cells, macrophages, and hematopoietic cells.
The therapeutic agent of claim 1, further comprising one or more of a checkpoint inhibitor, a targeted therapy, and a small molecule tumor inhibitor.
The therapeutic agent of claim 1, further comprising a safety switch agent selected from t-EGFR, Rituximab-CD34-Rituximab (RQR), and inducible caspase-9.
The therapeutic agent of claim 1, wherein the transmembrane domain of the CAR is selected from the group consisting of a T cell receptor α chain, a T cell receptor β chain, a CD3 zeta chain, a CD28, a CD3ε, a CD45, a CD4, a CD5, a CD8, a CD9, a CD16, a CD22, a CD33, a CD37, a CD64, a CD80, a CD86, a CD134, a CD137, an ICOS, a CD154, and a GITR.
The therapeutic agent of claim 1, wherein the transmembrane domain of the CAR comprises a transmembrane domain of a CD8.
The therapeutic agent of claim 1, wherein the co-stimulatory domain of the CAR is selected from the group consisting of a CD28, a 4-1BB, a GITR, an ICOS-1, a CD27, an OX-40, and a DAP10.
The therapeutic composition of claim 1, wherein the co-stimulatory domain of the CAR comprises a 4-1BB co-stimulatory domain.
The therapeutic agent of claim 1, wherein the activating domain of the CAR comprises a CD3 zeta activating domain.
The therapeutic agent of claim 1, wherein the transmembrane domain of the CAR comprises a transmembrane domain of a CD8, the co-stimulatory domain comprises a 4-1BB co-stimulatory domain, and the activating domain comprises a CD3 zeta activating domain.
The therapeutic agent of claim 1, wherein the CAR comprises the amino acid sequence of SEQ ID NO:
- 17.
The therapeutic agent of claim 1, wherein the tumors are BCMA-positive.
The therapeutic agent of claim 1, wherein the tumors are selected from ovarian, colon, pancreatic, melanoma, and cervical tumors.
A method of inhibiting growth of a tumor, the method comprising administering to a patient having a tumor an effective number of immune cells expressing an anti-BCMA chimeric antigen receptor (CAR) having an anti-BCMA single-chain variable fragment (scFv) comprising:
- a. a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO:
- 3, and a light chain variable region VL) comprising the amino acid sequence of SEQ ID NO:
- 5;
- b. a transmembrane domain;
- c. a co-stimulatory domain;
- and
- d. an activating domain;
- and further comprising an excipient.
The method of claim 16, wherein the immune cells are selected from T cells, NK cells, macrophages, and hematopoietic cells.
The method of claim 16, further comprising administering to the patient one or more of a checkpoint inhibitor, a targeted therapy or a small molecule tumor inhibitor.
The method of claim 16, further comprising administering to the patient a safety switch agent selected from t-EGFR, Rituximab-CD34-Rituximab (RQR), and inducible caspase-9.
The method of claim 16, wherein the transmembrane domain of the CAR is selected from the group consisting of a T cell receptor α chain, a T cell receptor β chain, a CD3 zeta chain, a CD28, a CD3ε, a CD45, a CD4, a CD5, a CD8, a CD9, a CD16, a CD22, a CD33, a CD37, a CD64, a CD80, a CD86, a CD134, a CD137, an ICOS, a CD154, and a GITR.
The method of claim 16, wherein the transmembrane domain of the CAR comprises a transmembrane domain of a CD8.
The method of claim 16, wherein the co-stimulatory domain of the CAR is selected from the group consisting of a CD28, a 4-1BB, a GITR, an ICOS-1, a CD27, an OX-40, and a DAP10.
The method of claim 16, wherein the co-stimulatory domain of the CAR comprises a 4-1BB co-stimulatory domain.
The method of claim 16, wherein the activating domain of the CAR comprises a CD3 zeta activating domain.
The method of claim 16, wherein the transmembrane domain of the CAR comprises a transmembrane domain of a CD8, the co-stimulatory domain comprises a 4-1BB co-stimulatory domain, and the activating domain comprises a CD3 zeta activating domain.
The method of claim 16, wherein the CAR comprises the amino acid sequence of SEQ ID NO:
- 17.
The method of claim 16, wherein the tumor is BCMA-positive.
The method of claim 16, wherein the tumor is selected from ovarian, colon, pancreatic, melanoma, and cervical tumor.
Dependencies are inferred from the claim text.