ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR-2 CHIMERIC ANTIGEN RECEPTORS AND USE OF SAME FOR THE TREATMENT OF CANCER

• US 20120213783A1
• Filed: 09/14/2010
• Published: 08/23/2012
• Est. Priority Date: 10/01/2009
• Status: Active Grant

• Current Assignee: United States Department Of Health And Human Services
• Original Assignee: United States Department Of Health And Human Services
• Inventors: Rosenberg, Steven A., Chinnasamy, Dhanalakshmi
• Granted Patent: US 8,465,743 B2
• Time in Patent Office: Days
• US Class Current: 424/134.1
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07K 14/7051 T-cell receptor (TcR)-CD3 complex
• CPC Class Codes: C07K 14/70521 CD28, CD152
• CPC Class Codes: C07K 16/2863 against receptors for growth factors, growth regulators
• CPC Class Codes: C07K 16/42 against immunoglobulins
• CPC Class Codes: G01N 33/5091 for testing the pathological state of an organism

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.

Claims

1. A chimeric antigen receptor (CAR) 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 T cell receptor signaling domain.

2. The CAR according to claim 1, wherein the antigen binding domain comprises an amino acid sequence comprising SEQ ID NO:

1 or 2.

3. The CAR according to claim 1, further comprising an intracellular hinge domain.

4. The CAR according to claim 3, wherein the extracellular hinge domain, transmembrane domain, and intracellular hinge domain comprise CD8 (SEQ ID NO:

3).

5. The CAR according to claim 1, wherein the extracellular hinge domain and transmembrane domain comprise CD8 (SEQ ID NO:

4).

6. The CAR according to claim 1, wherein the intracellular T cell receptor signaling domain comprises CD28, 4-1BB, and/or CD3ζ

(SEQ ID NO;

5 or

     6).

7. The CAR according to claim 1, wherein the extracellular hinge domain, transmembrane domain, and intracellular T cell signaling domain comprise CD28 (SEQ ID NO:

7) and/or CD3ζ

(SEQ ID NO;

     8).

8. The CAR according to claim 5, wherein the intracellular T cell receptor signaling domain comprises CD28 and/or CD3ζ

(SEQ ID NO;

     9).

9. The CAR according to claim 1 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs:

10-15.

10. A nucleic acid comprising a nucleotide sequence encoding the CAR according to claim 1.

11. The nucleic acid according to claim 10, comprising a nucleotide sequence selected from the group consisting of SEQ ID NOs:

16-21.

12. A recombinant expression vector comprising the nucleic acid of claim 10.

13. An isolated host cell comprising the recombinant expression vector of claim 12.

14. A population of cells comprising at least one host cell of claim 13.

15. An antibody, or antigen binding portion thereof, which specifically binds to a CAR according to claim 1.

16. A pharmaceutical composition comprising the CAR of claim 1 and a pharmaceutically acceptable carrier.

17. A method of detecting the presence of cancer in a host, comprising:

(a) contacting a sample comprising one or more cells from the host with the CAR of claim 1 thereby forming a complex, and

(b) detecting the complex, wherein detection of the complex is indicative of the presence of cancer in the host.

19. A method of treating or preventing cancer in a host comprising administering to the host the CAR of claim 1 in an amount effective to treat or prevent cancer in the host.

18. (canceled)