CHIMERIC ANTIGEN RECEPTORS TARGETING B-CELL MATURATION ANTIGEN

• US 20150051266A1
• Filed: 03/15/2013
• Published: 02/19/2015
• Est. Priority Date: 04/11/2012
• Status: Active Grant

• Current Assignee: United States Department Of Health And Human Services (Government of the United States of America)
• Original Assignee: The United States of America As Represented By The Secretary of Agriculture
• Inventors: Kochenderfer, James Noble
• Granted Patent: US 9,765,342 B2
• Time in Patent Office: Days
• US Class Current: 514/44.R
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 14/70503 Immunoglobulin superfamily
• CPC Class Codes: C07K 14/7051 T-cell receptor (TcR)-CD3 complex
• CPC Class Codes: C07K 14/70517 CD8
• CPC Class Codes: C07K 14/70521 CD28, CD152
• CPC Class Codes: C07K 14/70578 NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95 NGF-receptor C07K14/71, TNF-receptor C07K14/7151
• CPC Class Codes: C07K 16/18 against material from animals or humans
• CPC Class Codes: C07K 16/2878 against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
• CPC Class Codes: C07K 2317/73 Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
• CPC Class Codes: C07K 2319/00 Fusion polypeptide
• CPC Class Codes: C07K 2319/03 containing a transmembrane segment
• CPC Class Codes: C12N 15/62 DNA sequences coding for fusion proteins

Abstract

The invention provides an isolated and purified nucleic acid sequence encoding a chimeric antigen receptor (CAR) directed against B-cell Maturation Antigen (BCMA). The invention also provides host cells, such as T-cells or natural killer (NK) cells, expressing the CAR and methods for destroying multiple myeloma cells.

Claims

1. An isolated or purified nucleic acid sequence encoding a chimeric antigen receptor (CAR), wherein the CAR comprises an antigen recognition moiety and a T-cell activation moiety, and wherein the antigen recognition moiety is directed against B-cell Maturation Antigen (BCMA).

2. The isolated or purified nucleic acid sequence of claim 1, wherein the antigen recognition moiety comprises a monoclonal antibody directed against BCMA, or an antigen-binding portion thereof.

3. The isolated or purified nucleic acid sequence of claim 2, wherein the antigen recognition moiety comprises a variable region of a monoclonal antibody directed against BCMA.

4. The isolated or purified nucleic acid sequence of claim 1, wherein the T-cell activation moiety comprises a T-cell signaling domain of any one of the following proteins:

a human CD8-alpha protein, a human CD28 protein, a human CD3-zeta protein, a human FcRγ

protein, a CD27 protein, an OX40 protein, a human 4-1BB protein, modified versions of any of the foregoing, or any combination of the foregoing.

5. The isolated or purified nucleic acid sequence of claim 1, which comprises the nucleic acid sequence of SEQ ID NO:

1, SEQ ID NO;

2, or SEQ ID NO;

3

6. An isolated or purified CAR encoded by the nucleic acid sequence of claim 1.

7. The isolated or purified CAR of claim 6, which comprises the amino acid sequence of SEQ ID NO:

4, SEQ ID NO;

5, SEQ ID NO;

6, SEQ ID NO;

8, SEQ ID NO;

9, SEQ ID NO;

10, SEQ ID NO;

11, or SEQ ID NO;

12.

8. A vector comprising the isolated or purified nucleic acid sequence of claim 1.

9. An isolated host cell which expresses the nucleic acid sequence of claim 1.

10. The isolated host cell of claim 9, which expresses a CAR comprising an amino acid sequence of SEQ ID NO:

4, SEQ ID NO;

5, SEQ ID NO;

6, SEQ ID NO;

8, SEQ ID NO;

9, SEQ ID NO;

10, SEQ ID NO;

11, or SEQ ID NO;

12.

11. The isolated host cell of claim 9, which is a T-cell.

12. The isolated host cell of claim 9, which is a natural killer (NK) cell.

13. A method of destroying cancer cells, which method comprises contacting cancer cells that express BCMA with the isolated or purified nucleic acid sequence of claim 1, whereby the CAR is produced and binds to BCMA on the cancer cells and the cancer cells are destroyed.

14. A method of destroying cancer cells, which method comprises contacting cancer cells that express BCMA with the vector of claim 8, whereby the CAR is produced and binds to BCMA on the cancer cells and the cancer cells are destroyed.

15. A method of destroying cancer cells, which method comprises contacting cancer cells that express BCMA with one or more of the isolated T-cells of claim 11, whereby the CAR is produced and binds to BCMA on the cancer cells and the cancer cells are destroyed.

16. A method of destroying cancer cells, which method comprises contacting cancer cells that express BCMA with one or more of the isolated NK cells of claim 12, whereby the CAR is produced and binds to BCMA on the cancer cells and the cancer cells are destroyed.

17. The method of claim 13, wherein the cancer cells are in a human.

18. The method of claim 13, wherein the cancer cells are in vitro.

19. The method claim 13, wherein the cancer cells are multiple myeloma or Hodgkin'"'"'s lymphoma cells.