Use of chimeric antigen receptor modified cells to treat cancer

• US 10,654,934 B2
• Filed: 02/15/2018
• Issued: 05/19/2020
• Est. Priority Date: 04/01/2016
• Status: Active Grant

• Current Assignee: Innovative Cellular Therapeutics Holdings, Ltd.
• Original Assignee: Innovative Cellular Therapeutics Co., Ltd.
• Inventors: Xiao, Lei, Wu, Zhao, Pu, Chengfei, Cao, Zhiyuan, Sun, He, Bi, Mao
• Primary Examiner(s): Yu, Misook
• Application Number:
  US15/897,743
• Publication Number:
  US 20180179289A1
• Time in Patent Office: 824 Days
• Field of Search: None
• CPC Class Codes: A61K 2039/812 Breast
• CPC Class Codes: A61K 2039/82 Colon
• CPC Class Codes: A61K 2039/828 Stomach
• CPC Class Codes: A61K 2039/892 Reproductive system [uterus, ovaries, cervix, testes]
• CPC Class Codes: A61K 2239/38 characterised by the dose, timing or administration schedule
• CPC Class Codes: A61K 2239/48 Blood cells, e.g. leukemia or lymphoma
• CPC Class Codes: A61K 2239/49 Breast
• CPC Class Codes: A61K 39/4611 T-cells, e.g. tumor infiltrating lymphocytes [TIL], lymphokine-activated killer cells [LAK] or regulatory T cells [Treg]
• CPC Class Codes: A61K 39/4631 Chimeric Antigen Receptors [CAR]
• CPC Class Codes: A61K 39/464402 Receptors, cell surface antigens or cell surface determinants
• CPC Class Codes: A61K 39/464416 Receptors for cytokines
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07K 14/59 Follicle-stimulating hormone [FSH]; Chorionic gonadotropins, e.g.hCG [human chorionic gonadotropin]; Luteinising hormone [LH]; Thyroid-stimulating hormone [TSH]
• CPC Class Codes: C07K 14/70503 Immunoglobulin superfamily
• CPC Class Codes: C07K 14/70507 CD2
• CPC Class Codes: C07K 14/7051 T-cell receptor (TcR)-CD3 complex
• CPC Class Codes: C07K 14/70521 CD28, CD152
• CPC Class Codes: C07K 14/70532 B7 molecules, e.g. CD80, CD86
• 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 14/721 Steroid/thyroid hormone superfamily, e.g. GR, EcR, androgen receptor, oestrogen receptor
• CPC Class Codes: C07K 16/2809 : against the T-cell receptor (TcR)-CD3 complex
• CPC Class Codes: C07K 16/2869 : against hormone receptors for antibodies against neuromediator receptors C07K16/286
• CPC Class Codes: C07K 2317/24 : containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/622 : Single chain antibody (scFv)
• CPC Class Codes: C07K 2317/92 : Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
• CPC Class Codes: C07K 2319/03 : containing a transmembrane segment

Abstract

The present disclosure relates to compositions and methods for compositions, methods, and kits for treating cancer using chimeric antigen receptor (CAR) modified cells. Some embodiments of the present disclosure relate to an isolated nucleic acid sequence encoding CAR. The CAR may include an antigen binding domain, a transmembrane domain, a costimulatory signaling region, and a CD3 zeta signaling domain. The antigen binding domain may bind to an antigen of a non-essential organ.

Claims

1. A chimeric antigen receptor (CAR), wherein the CAR comprises an extracellular domain, a transmembrane domain, and an intracellular domain, and wherein the extracellular domain comprises amino acid sequence SEQ ID NO:

5.

2. The CAR of claim 1, wherein the CAR comprises amino acid sequence SEQ ID NO:

37.

3. The isolated nucleic acid sequence of claim 1, wherein the intracellular domain comprises a CD3 zeta signaling domain.

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

5. A composition comprising the CAR of claim 1 and a carrier.

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

7. A nucleic acid encoding the CAR of claim 1.

8. A vector comprising the nucleic acid of claim 7.

9. A cell comprising the nucleic acid of claim 7.

10. A population of cells comprising the nucleic acid of claim 7.

11. The population of cells of claim 10, wherein the population of cells comprises T cells.

12. A pharmaceutical composition comprising the population of T cells of claim 11.

13. A method of stimulating an anti-tumor immune response in a subject in need thereof, the method comprising administering an effective amount of the pharmaceutical composition of claim 12 to the subject, thereby stimulating anti-tumor immune response.

14. The method of claim 13, wherein the subject is diagnosed with thyroid cancer.

15. A method of stimulating an immune response in a population of cells expressing thyroid stimulating hormone receptor (TSHR), the method comprising contacting the population of cells with an effective amount of the pharmaceutical composition of claim 12.

16. The method of claim 15, wherein the immune response is a T cell-mediated immune response.

17. The method of claim 15, wherein the population of cells are in a subject.

18. The method of claim 15, where the immune response is an anti-tumor immune response.

19. A nucleic acid encoding the CAR of claim 2.

20. A nucleic acid encoding the CAR of claim 3.

21. A nucleic acid encoding the CAR of claim 4.

22. A vector comprising the nucleic acid of claim 19.

23. A vector comprising the nucleic acid of claim 20.

24. A vector comprising the nucleic acid of claim 21.

25. A cell comprising the nucleic acid of claim 19.

26. A cell comprising the nucleic acid of claim 20.

27. A cell comprising the nucleic acid of claim 21.

28. A population of cells comprising the nucleic acid of claim 19.

29. A population of cells comprising the nucleic acid of claim 20.

30. A population of cells comprising the nucleic acid of claim 21.

31. A pharmaceutical composition comprising the population of cells of claim 28.

32. A pharmaceutical composition comprising the population of cells of claim 29.

33. A pharmaceutical composition comprising the population of cells of claim 30.