Chimeric antigen receptors targeting HER2

Patent metadata

Field	Value
Publication number	US-11197919-B2
Application number	US-201615773754-A
Country	US
Kind code	B2
Filing date	Nov 4, 2016
Priority date	Nov 4, 2015
Publication date	Dec 14, 2021
Grant date	Dec 14, 2021

Abstract

Chimeric transmembrane immunoreceptors (CAR) which include an extracellular domain targeted to HER2, a transmembrane region, a costimulatory domain and an intracellular signaling domain are described.

First claim

What is claimed is:

1. A nucleic acid molecule encoding a chimeric antigen receptor, wherein the chimeric antigen receptor comprises the amino acid sequence of any of SEQ ID NOs: 34-41.

2. An isolated population of human T cells transduced by a vector comprising an expression cassette encoding a chimeric antigen receptor, wherein the chimeric antigen receptor comprises the amino acid sequence of any of SEQ ID NOs: 34-41.

3. A method of treating a HER2 expressing brain cancer in a patient comprising administering a population of autologous or allogeneic human T cells transduced by a vector comprising an expression cassette encoding a chimeric antigen receptor, wherein chimeric antigen receptor comprises an amino acid sequence selected from SEQ ID NOs:34-41.

4. The method of claim 3 wherein the population of human T cells comprise CD62L+ memory T cells.

5. The method claim 3 wherein the cancer is a breast to brain metastasis.

6. The method of claim 3 , wherein the transduced human T cells where prepared by a method comprising obtaining T cells from the patient, treating the T cells to isolate central memory T cells, and transducing at least a portion of the central memory cells to with a viral vector comprising an expression cassette encoding a chimeric antigen receptor, wherein chimeric antigen receptor comprises an amino acid sequence selected from SEQ ID NOs:34-41.

7. The method of claim 3 wherein the T cells are administered intratumorally.

8. The method of claim 3 wherein the T cells are administered intraventricularly.

9. The method of claim 3 wherein the T cells are administered intravetricularly adjacent to a tumor.

10. An isolated T cell expressing a polypeptide or a chimeric antigen receptor comprising an amino acid sequence that is identical to an amino acid sequence selected from SEQ ID NOs:26-41.

11. The nucleic acid molecule of claim 1 , wherein the chimeric antigen receptor comprises the amino acid sequence of SEQ ID NO: 34.

12. The nucleic acid molecule of claim 1 , wherein the chimeric antigen receptor comprises the amino acid sequence of SEQ ID NO: 35.

13. The nucleic acid molecule of claim 1 , wherein the chimeric antigen receptor comprises the amino acid sequence of SEQ ID NO: 36.

14. The nucleic acid molecule of claim 1 , wherein the chimeric antigen receptor comprises the amino acid sequence of SEQ ID NO: 37.

15. The nucleic acid molecule of claim 1 , wherein the chimeric antigen receptor comprises the amino acid sequence of SEQ ID NO: 38.

16. The nucleic acid molecule of claim 1 , wherein the chimeric antigen receptor comprises the amino acid sequence of SEQ ID NO: 39.

17. The nucleic acid molecule of claim 1 , wherein the chimeric antigen receptor comprises the amino acid sequence of SEQ ID NO: 40.

18. The nucleic acid molecule of claim 1 , wherein the chimeric antigen receptor comprises the amino acid sequence of SEQ ID NO: 41.

19. A nucleic acid molecule encoding a polypeptide, wherein the polypeptide comprises the amino acid sequence of any of SEQ ID NOs: 26-33.

20. The nucleic acid molecule of claim 19 , wherein the polypeptide comprises the amino acid sequence of SEQ ID NO: 26.

21. The nucleic acid molecule of claim 19 , wherein the polypeptide comprises the amino acid sequence of SEQ ID NO: 27.

22. The nucleic acid molecule of claim 19 , wherein the polypeptide comprises the amino acid sequence of SEQ ID NO: 28.

23. The nucleic acid molecule of claim 19 , wherein the polypeptide comprises the amino acid sequence of SEQ ID NO: 29.

24. The nucleic acid molecule of claim 19 , wherein the polypeptide comprises the amino acid sequence of SEQ ID NO: 30.

25. The nucleic acid molecule of claim 19 , wherein the polypeptide comprises the amino acid sequence of SEQ ID NO: 31.

26. The nucleic acid molecule of claim 19 , wherein the polypeptide comprises the amino acid sequence of SEQ ID NO: 32.

27. The nucleic acid molecule of claim 19 , wherein the polypeptide comprises the amino acid sequence of SEQ ID NO: 33.

28. An isolated population of human T cells transduced by a vector comprising an expression cassette encoding a polypeptide, wherein the polypeptide comprises the amino acid sequence of any of SEQ ID NOs: 26-33.

29. The isolated population of human T cells of claim 28 , wherein the polypeptide comprises the amino acid sequence of SEQ ID NO: 26.

30. The isolated population of human T cells of claim 28 , wherein the polypeptide comprises the amino acid sequence of SEQ ID NO: 27.

31. The isolated population of human T cells of claim 28 , wherein the polypeptide comprises the amino acid sequence of SEQ ID NO: 28.

32. The isolated population of human T cells of claim 28 , wherein the polypeptide comprises the amino acid sequence of SEQ ID NO: 29.

33. The isolated population of human T cells of claim 28 , wherein the polypeptide comprises the amino acid sequence of SEQ ID NO: 30.

34. The isolated population of human T cells of claim 28 , wherein the polypeptide comprises the amino acid sequence of SEQ ID NO: 31.

35. The isolated population of human T cells of claim 28 , wherein the polypeptide comprises the amino acid sequence of SEQ ID NO: 32.

36. The isolated population of human T cells of claim 28 , wherein the polypeptide comprises the amino acid sequence of SEQ ID NO: 33.

37. The isolated population of human T cells of claim 18 , wherein the chimeric antigen receptor comprises the amino acid sequence of SEQ ID NO: 34.

38. The isolated population of human T cells of claim 18 , wherein the chimeric antigen receptor comprises the amino acid sequence of SEQ ID NO: 35.

39. The isolated population of human T cells of claim 18 , wherein the chimeric antigen receptor comprises the amino acid sequence of SEQ ID NO: 36.

40. The isolated population of human T cells of claim 18 , wherein the chimeric antigen receptor comprises the amino acid sequence of SEQ ID NO: 37.

41. The isolated population of human T cells of claim 18 , wherein the chimeric antigen receptor comprises the amino acid sequence of SEQ ID NO: 38.

42. The isolated population of human T cells of claim 18 , wherein the chimeric antigen receptor comprises the amino acid sequence of SEQ ID NO: 39.

43. The isolated population of human T cells of claim 18 , wherein the chimeric antigen receptor comprises the amino acid sequence of SEQ ID NO: 40.

44. The isolated population of human T cells of claim 18 , wherein the chimeric antigen receptor comprises the amino acid sequence of SEQ ID NO: 41.

45. The isolated T cell of claim 10 , wherein the polypeptide or chimeric antigen receptor comprises an amino acid sequence that is identical to SEQ ID NO:26.

46. The isolated T cell of claim 10 , wherein the polypeptide or chimeric antigen receptor comprises an amino acid sequence that is identical to SEQ ID NO:27.

47. The isolated T cell of claim 10 , wherein the polypeptide or chimeric antigen receptor comprises an amino acid sequence that is identical to SEQ ID NO: 28.

48. The isolated T cell of claim 10

Assignees

• Hope City

Inventors

• Priceman Saul J
• Forman Stephen J
• Brown Christine E

Classifications

• A61K40/31

  Chimeric antigen receptors [CAR] · CPC title

• A61K40/11

  T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer [LAK] cells · CPC title

• A61K40/4205

  Her-2/neu/ErbB2, Her-3/ErbB3 or Her 4/ ErbB4 · CPC title

• A61K40/50

  characterised by the use of allogeneic cells · CPC title

• C07K14/70521 Primary

  CD28, CD152 · CPC title