IP Library › Granted Patent US 10,767,184
Granted Patent B2
US 10,767,184 · App. 15/692,473 · Granted Sep 8, 2020

Chimeric antigen receptors targeting B-cell maturation antigen

Inventor: James N. Kochenderfer (Bethesda, MD)
Assignee: The United States of America, as represented by the Secretary, Dept. of Health and Human Services
C12N15/62C07K14/7051C07K14/70503C07K14/70517C07K14/70521C07K14/70578C07K16/18C07K16/2878A61K48/00A61K2039/505C07K2317/73C07K2319/00C07K2319/03
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Quick Facts
Patent No.
US 10,767,184
App. No.
15/692,473
Granted
Sep 8, 2020
Kind
B2
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 (59)

1. A chimeric antigen receptor (CAR) comprising an antigen recognition moiety directed against B-cell Maturation Antigen (BCMA), a transmembrane domain, and one or more intracellular T cell signaling domains.

2. The CAR of claim 1 , wherein the antigen recognition moiety comprises a monoclonal antibody directed against BCMA, or an antigen-binding fragment thereof.

3. The CAR of claim 1 , wherein the antigen recognition moiety comprises a variable region of a monoclonal antibody directed against BCMA, or an antigen-binding fragment thereof.

4. The CAR of claim 3 , wherein the variable region is a heavy chain variable region.

5. The CAR of claim 1 , wherein the antigen recognition moiety comprises an antigen binding fragment of a monoclonal antibody directed against BCMA.

6. The CAR of claim 5 , wherein the antigen binding fragment is selected from the group consisting of: a Fab fragment, a F(ab′) 2 fragment, an Fv fragment, a single chain variable fragment (scFv), and a diabody.

7. The CAR of claim 5 , wherein the antigen binding fragment comprises an scFv.

8. The CAR of claim 1 , wherein the transmembrane domain is selected from the group consisting of: a CD28 transmembrane domain and a CD8 alpha transmembrane domain.

9. The CAR of claim 1 , wherein the one or more intracellular T cell signaling domains are isolated from a protein selected from the group consisting of: CD28, CD3ζ, FcRγ, CD27, OX40, and 4-1BB protein.

10. The CAR of claim 1 , wherein the one or more intracellular T cell signaling domains comprises a CD28 intracellular T cell signaling domain.

11. The CAR of claim 10 , wherein the one or more intracellular T cell signaling domains further comprises a CD3ζ intracellular T cell signaling domain.

12. The CAR of claim 11 , wherein the one or more intracellular T cell signaling domains further comprises an OX40 intracellular T cell signaling domain.

13. The CAR of claim 1 , wherein the one or more intracellular T cell signaling domains comprises a FcRγ intracellular T cell signaling domain.

14. The CAR of claim 13 , wherein the one or more intracellular T cell signaling domains further comprises a CD3ζ intracellular T cell signaling domain.

15. The CAR of claim 1 , wherein the one or more intracellular T cell signaling domains comprises a CD27 intracellular T cell signaling domain.

16. The CAR of claim 15 , wherein the one or more intracellular T cell signaling domains further comprises a CD3ζ intracellular T cell signaling domain.

17. The CAR of claim 1 , wherein the one or more intracellular T cell signaling domains comprises a OX40 intracellular T cell signaling domain.

18. The CAR of claim 17 , wherein the one or more intracellular T cell signaling domains further comprises a CD3ζ intracellular T cell signaling domain.

19. The CAR of claim 18 , wherein the one or more intracellular T cell signaling domains further comprises a 4-1BB intracellular T cell signaling domain.

20. The CAR of claim 1 , wherein the one or more intracellular T cell signaling domains comprises a 4-1BB intracellular T cell signaling domain.

21. The CAR of claim 20 , wherein the one or more intracellular T cell signaling domains further comprises a CD3ζ intracellular T cell signaling domain.

22. The CAR of claim 1 , further comprising a signal sequence polypeptide.

23. The CAR of claim 22 , wherein the signal sequence polypeptide is a granulocyte macrophage-colony stimulating factor (GM-CSF) signal sequence polypeptide or a CD8α signal sequence polypeptide.

24. The CAR of claim 1 , further comprising a hinge domain.

25. The CAR of claim 24 , wherein the hinge domain is a CD8α hinge domain or a CD28 hinge domain.

26. A CAR comprising: a signal sequence polypeptide; an antibody or antigen binding fragment thereof directed against BCMA; a CD8α hinge domain or a CD28 hinge domain; a CD8α transmembrane domain or a CD28 transmembrane domain; a 4-1BB intracellular T cell signaling domain, an OX40 intracellular T cell signaling domain, or a CD28 intracellular T cell signaling domain; and a CD3ζ intracellular T cell signaling domain.

27. The CAR of claim 26 , wherein the CAR comprises the signal sequence polypeptide; the antibody or antigen binding fragment thereof directed against BCMA; the CD8α hinge domain; the CD8α transmembrane domain; the 4-1BB intracellular T cell signaling domain; and the CD3ζ intracellular T cell signaling domain.

28. The CAR of claim 26 , wherein the CAR comprises the signal sequence polypeptide; the antibody or antigen binding fragment thereof directed against BCMA; the CD8α hinge domain; the CD8α transmembrane domain; the OX40 intracellular T cell signaling domain; and the CD3ζ intracellular T cell signaling domain.

29. The CAR of claim 26 , wherein the CAR comprises the signal sequence polypeptide; the antibody or antigen binding fragment thereof directed against BCMA; the CD8α hinge domain; the CD8α transmembrane domain; the CD28 intracellular T cell signaling domain; and the CD3ζ intracellular T cell signaling domain.

30. The CAR of claim 26 , wherein the CAR comprises the signal sequence polypeptide; the antibody or antigen binding fragment thereof directed against BCMA; the CD8α hinge domain; the CD28 transmembrane domain; the CD28 intracellular T cell signaling domain; and the CD3ζ intracellular T cell signaling domain.

31. The CAR of claim 26 , wherein the CAR comprises the signal sequence polypeptide; the antibody or antigen binding fragment thereof directed against BCMA; the CD28 hinge domain; the CD28 transmembrane domain; the CD28 intracellular T cell signaling domain; and the CD3ζ intracellular T cell signaling domain.

32. A CAR comprising: a CD8α signal sequence polypeptide; an scFv directed against BCMA; a CD8α hinge domain or a CD28 hinge domain; a CD8α transmembrane domain or a CD28 hinge domain; a 4-1BB intracellular T cell signaling domain, an OX40 intracellular T cell signaling domain, or a CD28 intracellular T cell signaling domain; and a CD3ζ intracellular T cell signaling domain.

33. The CAR of claim 32 comprising: the CD8α signal sequence polypeptide; the scFv directed against BCMA; the CD8α hinge domain; the CD8α transmembrane domain; a 4-1BB intracellular T cell signaling domain; and the CD3ζ intracellular T cell signaling domain.

34. The CAR of claim 32 comprising: the CD8α signal sequence polypeptide; the scFv directed against BCMA; the CD8α hinge domain; the CD8α transmembrane domain; the OX40 intracellular T cell signaling domain; and the CD3ζ intracellular T cell signaling domain.

35. The CAR of claim 32 comprising: the CD8α signal sequence polypeptide; the scFv directed against BCMA; the CD8α hinge domain; the CD8α transmembrane domain; the CD28 intracellular T cell signaling domain; and the CD3ζ intracellular T cell signaling domain.

36. The CAR of claim 32 comprising: the CD8α signal sequence polypeptide; the scFv directed against BCMA; the CD8α hinge domain; the CD28 transmembrane domain; the CD28 intracellular T cell signaling domain; and the CD3ζ intracellular T cell signaling domain.

37. The CAR of claim 32 comprising: the CD8α signal sequence polypeptide; the scFv directed against BCMA; the CD28 hinge domain; the CD28 transmembrane domain; the CD28 intracellular T cell signaling domain; and the CD3ζ intracellular T cell signaling domain.

38. A vector comprising a polynucleotide encoding the CAR of claim 1 .

39. The vector of claim 38 , wherein the polynucleotide comprises ribonucleotides.

40. The vector of claim 39 , wherein the vector is a viral vector.

41. The vector of claim 40 , wherein the viral vector is a retroviral vector.

42. The vector of claim 41 , wherein the retroviral vector is a lentiviral vector.

43. An isolated host cell comprising a vector that comprises a polynucleotide encoding the CAR of claim 1 .

44. The isolated host cell of claim 43 , wherein the polynucleotide comprises ribonucleotides.

45. The isolated host cell of claim 44 , wherein the vector is a viral vector.

46. The isolated host cell of claim 44 , wherein the vector is a retroviral vector.

47. The isolated host cell of claim 44 , wherein the vector is a lentiviral vector.

48. The isolated host cell of claim 44 , wherein the host cell is a natural killer (NK) cell.

49. The isolated host cell of claim 44 , wherein the host cell is a T cell.

50. The isolated host cell of claim 49 , wherein the T cell is a CD4+ T cell.

51. The isolated host cell of claim 49 , wherein the T cell is a CD8+ T cell.

52. The isolated host cell of claim 49 , wherein the T cell is a memory T cell.

53. The isolated host cell of claim 49 , wherein the T cell is a tumor infiltrating T cell.

54. The isolated host cell of claim 48 , wherein the polynucleotide comprises ribonucleotides.

55. The isolated host cell of claim 49 , wherein the polynucleotide comprises ribonucleotides.

56. The isolated host cell of claim 50 , wherein the polynucleotide comprises ribonucleotides.

57. The isolated host cell of claim 51 , wherein the polynucleotide comprises ribonucleotides.

58. The isolated host cell of claim 52 , wherein the polynucleotide comprises ribonucleotides.

59. The isolated host cell of claim 53 , wherein the polynucleotide comprises ribonucleotides.

Continuity (3)
Continuation 14389677
Provisional Application 61622600 · Apr 11, 2012
Related Publication 20180051292A1 · Feb 22, 2018
Cited By (2)
US 12,286,642 US 12,458,667