Use of ICOS-based CARS to enhance antitumor activity and CAR persistence

Patent metadata

Field	Value
Publication number	US-10577407-B2
Application number	US-201715637734-A
Country	US
Kind code	B2
Filing date	Jun 29, 2017
Priority date	Feb 22, 2012
Publication date	Mar 3, 2020
Grant date	Mar 3, 2020

Abstract

The present invention provides compositions and methods for treating cancer in a human. The invention includes administering a genetically modified Th17 cell to express a CAR having an antigen binding domain, a transmembrane domain, and an ICOS intracellular signaling domain.

First claim

What is claimed is:

1. A method of providing an anti-tumor immunity in a mammal, the method comprising administering to the mammal an effective amount of a T cell genetically modified to express a CAR, wherein the CAR comprises an antigen binding domain, an ICOS transmembrane domain, and an ICOS intracellular signaling domain, thereby providing an anti-tumor immunity in the mammal, wherein the ICOS transmembrane domain comprises the amino acid sequence of SEQ ID NO: 12, wherein the antigen binding domain binds to a tumor antigen, wherein the T cell is administered intratumorally, and wherein the T cell induces an immune response to a tumor expressing the tumor antigen and/or reduces tumor volume.

2. The method of claim 1 , wherein the CAR further comprises a CD3zeta signaling domain.

3. The method of claim 1 , wherein the CAR further comprises a costimulatory signaling region comprising the intracellular domain of a costimulatory molecule selected from the group consisting of CD27, CD28, 4-1BB, OX40, CD30, CD40, PD-1, lymphocyte function-associated antigen-1 (LFA-1), CD2, CD7, LIGHT, NKG2C, B7-H3, a ligand that specifically binds with CD83, and any combination thereof.

4. The method of claim 1 , wherein the ICOS intracellular signaling domain comprises the amino acid sequence of SEQ ID NO: 13.

5. The method of claim 1 , wherein the antigen binding domain comprises an anti-mesothelin antibody or fragment thereof.

6. A method of treating a human with a tumor, the method comprising administering to the human a cell genetically engineered to express a CAR, wherein the CAR comprises an antigen binding domain, an ICOS transmembrane domain, and an ICOS intracellular signaling domain, wherein the cell is selected from the group consisting of a Th17 cell and a Tc17 cell, wherein the ICOS transmembrane domain comprises the amino acid sequence of SEQ ID NO: 12, wherein the antigen binding domain binds to a tumor antigen, wherein the cell is administered intratumorally, and wherein the cell induces an immune response to a tumor expressing the tumor antigen and/or reduces tumor volume.

7. The method of claim 6 , wherein the CAR further comprises a CD3zeta signaling domain.

8. The method of claim 6 , wherein the CAR further comprises a costimulatory signaling region comprising the intracellular domain of a costimulatory molecule selected from the group consisting of CD27, CD28, 4-1BB, OX40, CD30, CD40, PD-1, lymphocyte function-associated antigen-1 (LFA-1), CD2, CD7, LIGHT, NKG2C, B7-H3, a ligand that specifically binds with CD83, and any combination thereof.

9. The method of claim 6 , wherein the ICOS intracellular signaling domain comprises the amino acid sequence of SEQ ID NO: 13.

10. The method of claim 6 , wherein the antigen binding domain comprises an anti-mesothelin antibody or fragment thereof.

11. The method of claim 6 , wherein the human is resistant to at least one chemotherapeutic agent.

12. The method of claim 1 , wherein the antigen is selected from PSMA, c-Met, Glycolipid F77, EGFRvIII, GD-2, NY-ESO-1 and MAGE A3.

13. The method of claim 6 , wherein the antigen is selected from PSMA, c-Met, Glycolipid F77, EGFRvIII, GD-2, NY-ESO-1 and MAGE A3.

14. The method of claim 1 , wherein the tumor is selected from mesothelioma, pancreatic cancer, ovarian cancer, triple negative breast cancer, non-small cell lung cancer, prostate cancer and glioblastoma.

15. The method of claim 6 , wherein the tumor is selected from mesothelioma, pancreatic cancer, ovarian cancer, triple negative breast cancer, non-small cell lung cancer, prostate cancer and glioblastoma.

Assignees

• Univ Pennsylvania

Inventors

• June Carl H
• Guedan Carrio Sonia
• Zhao Yangbing
• Scholler John

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• C07K14/70521

  CD28, CD152 · CPC title

• C07K14/70517

  CD8 · CPC title

• C07K2319/03

  containing a transmembrane segment · CPC title

• C07K2319/00

  Fusion polypeptide · CPC title