Anti-vascular endothelial growth factor receptor-2 chimeric antigen receptors and use of same for the treatment of cancer

Patent metadata

Field	Value
Publication number	US-9522955-B2
Application number	US-201414454820-A
Country	US
Kind code	B2
Filing date	Aug 8, 2014
Priority date	Oct 1, 2009
Publication date	Dec 20, 2016
Grant date	Dec 20, 2016

Abstract

The invention provides chimeric antigen receptors (CARs) comprising an antigen binding domain of a KDR-1121 or DC101 antibody, an extracellular hinge domain, a T cell receptor transmembrane domain, and an intracellular domain T cell receptor signaling domain. Nucleic acids, recombinant expression vectors, host cells, populations of cells, antibodies, or antigen binding portions thereof, and pharmaceutical compositions relating to the CARs are disclosed. Methods of detecting the presence of cancer in a host and methods of treating or preventing cancer in a host are also disclosed.

First claim

The invention claimed is:

1. A method of treating cancer in a host comprising administering to the host, in an amount effective to treat cancer in the host, a composition comprising a population of syngeneic T cells, wherein the cells express a chimeric antigen receptor (CAR), wherein the CAR comprises:
(a) an amino acid sequence comprising SEQ ID NO: 3, 4, or 7; and
(b) an amino acid sequence comprising SEQ ID NO: 5, 6, 8, or 9,
wherein the cancer expresses vascular endothelial growth factor receptor-2 (VEGFR-2), and
wherein (i) the host is a human and the CAR further comprises the amino acid sequence of SEQ ID NO: 1 or (ii) the host is a mouse and the CAR further comprises the amino acid sequence of SEQ ID NO: 2.

2. The method of claim 1 , wherein the composition further comprises a pharmaceutically acceptable carrier.

3. The method according to claim 1 , wherein the CAR comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 10-15.

4. The method according to claim 1 , wherein the CAR is encoded by a nucleotide sequence selected from the group consisting of SEQ NOs: 16-21.

5. The method according to claim 1 , wherein the cancer is melanoma.

6. The method according to claim 1 , wherein the cancer is colon cancer.

7. The method according to claim 1 , wherein the cancer is kidney cancer.

8. The method according to claim 1 , wherein the cancer is colon adenocarcinoma or colon carcinoma.

9. The method according to claim 1 , wherein the cancer is a solid tumor or hematologic malignancy.

10. The method according to claim 1 , wherein the cancer is renal carcinoma.

11. The method according to claim 1 , wherein the cancer is sarcoma.

12. The method according to claim 1 , wherein the cancer is a tumor comprising blood vessels, wherein the blood vessels comprise endothelial cells, and wherein the endothelial cells express VEGFR-2.

13. The method according to claim 1 , wherein the CAR comprises the amino acid sequences of:
(a) SEQ ID NOs: 1, 3, and 5;
(b) SEQ ID NOs: 1, 7, and 8;
(c) SEQ ID NOs: 2, 4, and 6;
(d) SEQ ID NOs: 2, 4, and 9;
(e) SEQ ID NOs: 2, 3, and 5; or
(f) SEQ ID NOs: 2, 7, and 8.

14. The method according to claim 1 , wherein the CAR comprises the amino acid sequences of SEQ ID NOs: 2, 3, and 5.

15. The method according to claim 1 , wherein the T cells are peripheral blood mononuclear cells.

16. The method according to claim 1 , wherein the T cells are primary T cells.

Assignees

• Us Health

Inventors

• Rosenberg Steven A
• Chinnasamy Dhanalakshmi

Classifications

• C07K16/42

  against immunoglobulins · CPC title

• C07K16/2863 Primary

  against receptors for growth factors, growth regulators · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• C07K14/70521

  CD28, CD152 · CPC title

• G01N33/5091

  for testing the pathological state of an organism · CPC title