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

Patent metadata

Field	Value
Publication number	US-9714278-B2
Application number	US-201314376038-A
Country	US
Kind code	B2
Filing date	Feb 22, 2013
Priority date	Feb 22, 2012
Publication date	Jul 25, 2017
Grant date	Jul 25, 2017

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. An isolated nucleic acid sequence encoding a chimeric antigen receptor (CAR), wherein the CAR comprises an antigen binding domain comprising an anti-mesothelin antibody or fragment thereof, a transmembrane domain, and an ICOS intracellular signaling domain having an amino acid sequence of SEQ ID NO:13.

2. The isolated nucleic acid sequence of claim 1 , further comprising a CD3zeta signaling domain.

3. An isolated nucleic acid sequence encoding a chimeric antigen receptor (CAR), wherein the CAR comprises an antigen binding domain comprising an anti-mesothelin antibody or fragment thereof, a transmembrane domain, and an ICOS intracellular signaling domain, the isolated nucleic acid comprising the nucleic acid sequence of SEQ ID NO: 8.

4. The isolated nucleic acid sequence of claim 1 , wherein the antigen binding domain is an antibody or an antigen-binding fragment thereof.

5. The isolated nucleic acid sequence of claim 4 , wherein the antigen-binding fragment is a Fab or a scFv.

6. The isolated nucleic acid sequence of claim 1 , further comprising 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.

7. The isolated nucleic acid sequence of claim 1 , wherein the ICOS intracellular signaling domain is encoded by the nucleic acid sequence of SEQ ID NO: 6.

8. The isolated nucleic acid sequence of claim 2 , wherein the CD3 zeta signaling domain is encoded by the nucleic acid sequence of SEQ ID NO: 7.

9. A cell comprising the nucleic acid sequence encoding a chimeric antigen receptor (CAR), wherein the CAR comprises an antigen binding domain comprising an anti-mesothelin antibody or fragment thereof, a transmembrane domain, and an ICOS intracellular signaling domain, comprising the amino acid sequence SEQ ID NO:13.

10. The cell of claim 9 , wherein the CAR further comprises a CD3zeta signaling domain.

11. The cell of claim 9 , wherein the nucleic acid sequence comprises the nucleic acid sequence of SEQ ID NO: 8.

12. The cell of claim 9 , wherein the antigen binding domain is an antibody or an antigen-binding fragment thereof.

13. The cell of claim 12 , wherein the antigen-binding fragment is a Fab or a scFv.

14. The cell of claim 9 , 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.

15. The cell of claim 9 , wherein the ICOS intracellular signaling domain is encoded by the nucleic acid sequence of SEQ ID NO: 6.

16. The cell of claim 10 , wherein the CD3 zeta signaling domain is encoded by the nucleic acid sequence of SEQ ID NO: 7.

17. The cell of claim 9 , wherein the cell is selected from the group consisting of a Th17 cell and a Tc17 cell.

18. The cell of claim 9 , wherein the cell exhibits an anti-tumor immunity when the antigen binding domain binds to its corresponding antigen.

Assignees

• Univ Pennsylvania

Inventors

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

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• C07K2319/00

  Fusion polypeptide · CPC title

• C07K14/70521

  CD28, CD152 · CPC title

• C07K14/70596

  Molecules with a "CD"-designation not provided for elsewhere · CPC title

• C07K14/70517

  CD8 · CPC title