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1. WO2020113224 - RÉCEPTEUR D'ANTIGÈNE CHIMÈRE ET PROCÉDÉS D'UTILISATION DE CELUI-CI

Note: Texte fondé sur des processus automatiques de reconnaissance optique de caractères. Seule la version PDF a une valeur juridique

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What is claimed:

1. An engineered cell comprising a chimeric antigen receptor, wherein the chimeric antigen receptor comprises an extracellular ligand binding domain that is specific for a first antigen and a second antigen on the surface of a cancer cell, wherein the first antigen comprises CAIX and the second antigen comprises CD70.

2. The engineered cell of claim 1, wherein the CAR further comprises a transmembrane polypeptide and an intracellular signaling domain.

3. The engineered cell of claim 2, wherein the CAR further comprises a co-stimulatory domain.

4. The engineered cell of claim 1, wherein the extracellular ligand binding domain comprises an antibody or fragment thereof.

5. The engineered cell of claim 4, wherein the antibody comprises a VH and/or VL according to Table 2, or any combination thereof.

6. The engineered cell of claim 4, wherein the antibody comprises a VH and/or VL according to Table 4, or any combination thereof.

7. The engineered cell of claim 4, wherein the extracellular binding domain comprises a a VH and/or a VL of Table 2 and Table 4, or any combination thereof.

8. The engineered cell of claim 4, wherein the antibody comprises a CDR1, CDR2, and/or CDR3 of Table 1, or any combination thereof.

9. The engineered cell of claim 4, wherein the antibody comprises a CDR1, CDR2, and/or CDR3 of Table 3, or any combination thereof.

10. The engineered cell of claim 4, wherein the extracellular binding domain comprises a CDR1, CDR2, and/or CDR3 of Table 1 and Table 3, or any combination thereof.

11. The engineered cell of claim 1, wherein the engineered cell expresses and secretes a recombinant polypeptide.

12 The engineered cell of claim 11, wherein the recombinant polypeptide comprises an antibody or fragment thereof, or a cytokine.

13. The engineered cell of claim 11, wherein the recombinant polypeptide modulates the immune system of a subject.

14. The engineered cell of claim 11, wherein the recombinant polypeptide is an immune checkpoint blockade antibody.

15. The engineered cell of claim 11, wherein the recombinant polypeptide modulates tumor vasculogenesis.

16. The engineered cell of claim 15, wherein the recombinant polypeptide is specific for VEGF, VEGFR1, VEGFR2, PDGF, Ang-1, or ATI.

17. The engineered cell of claim 11, wherein the recombinant polypeptide comprises an antibody or fragment thereof specific for TIGIT, GITR, PD-L1, PD-L2, PD-1, CTLA- 4, VISTA, CD70, TIM-3, LAG-3, CD40L, or CCR4.

18. The engineered cell of claim 12, wherein the cytokine comprises IL-12, IL-15, or IL- 18.

19. The engineered cell of claim 1 , wherein the cell comprises a T cell, an NK cell, or an NKT cell.

20. The engineered cell of claim 19, wherein the T cell is CD4+, CD8+, CD3+ panT cells, or any combination thereof.

21. The engineered cell of claim 19, wherein the T cell is a mixed population of CD4+ and CD8+ T cells.

22. A nucleic acid construct encoding a chimeric antigen receptor, wherein the chimeric antigen receptor comprises an extracellular ligand binding domain that is specific for a first antigen and a second antigen on the surface of a cancer cell, wherein the first antigen comprises CAIX and the second antigen comprises CD70.

23. The nucleic acid construct of claim 22, wherein the chimeric antigen receptor further comprises a transmembrane polypeptide and an intracellular signaling domain.

24. The nucleic acid construct of claim 23, wherein the chimeric antigen receptor further comprises a co-stimulatory domain.

25. The nucleic acid construct of claim 23, wherein the nucleic acid construct further encodes a recombinant polypeptide.

26. The nucleic acid construct of claim 25, wherein the recombinant polypeptide can be secreted from an engineered cell.

27. The nucleic acid construct of claim 25, wherein the recombinant polypeptide

comprises an antibody or fragment thereof, or a cytokine.

28. The nucleic acid construct of claim 25, wherein the recombinant polypeptide

modulates the immune system of a subject.

29. The nucleic acid construct of claim 25, wherein the recombinant polypeptide is an immune checkpoint blockade antibody.

30. The nucleic acid construct of claim 25, wherein the recombinant polypeptide

modulates tumor vasculogenesis.

31. The nucleic acid construct of claim 25, wherein the recombinant polypeptide

comprises an antibody or fragment thereof specific for TIGIT, GITR, PD-L1, PD-L2, PD-1, CTLA-4, VISTA, CD70, TIM-3, LAG-3, CD40L, or CCR4.

32. The nucleic acid of claim 27, wherein the cytokine comprises IL12, IL15 or IL18.

33. The nucleic acid of claim 30, wherein the recombinant polypeptide is specific for VEGF, VEGFR1, VEGFR2, PDGF, Ang-1, or ATI

34. A vector comprising the nucleic acid construct of claim 22.

35. A cell comprising the vector of claim 34.

36. A method for treating a subject afflicted with cancer, the method comprising administering the subject a therapeutically effective amount of the engineered cell of claim 1.

37. A method of reducing progression or promoting regression of a cancer in a subject, the method comprising administering the subject a therapeutically effective amount of the engineered cell of claim 1.

38. A method of reducing cellular proliferation of a cancer cell in a subject, the method the method comprising administering the subject a therapeutically effective amount of the engineered cell of claim 1.

39. The method of any one of claims 36-38, wherein cancer comprises renal cell

carcinoma.

40. A chimeric antigen receptor (CAR) comprising an extracellular ligand binding

domain, wherein the extracellular ligand binding domain is specific for a first antigen and a second antigen on the surface of a cancer cell, wherein the first antigen comprises CAIX and the second antigen comprises CD70.

41. The CAR of claim 40, wherein the CAR further comprises a transmembrane

polypeptide and an intracellular signaling domain.

42. The CAR of claim 41, wherein the CAR further comprises a co-stimulatory domain.

43. The CAR of claim 40, wherein the extracellular ligand binding domain comprises an antibody or fragment thereof.

44. A cell comprising the chimeric antigen receptor (CAR) of claim 40.

45. An engineered cell comprising a first chimeric antigen receptor and a second chimeric antigen receptor, wherein the first chimeric antigen receptor comprises an

extracellular ligand binding domain specific for CAIX, and wherein the second

chimeric antigen receptor comprises an extracellular ligand binding domain that is specific for CD70.

46. The engineered cell of claim 45, wherein the engineered cell expresses and secretes a recombinant polypeptide.

47. The engineered cell of claim 46, wherein the recombinant polypeptide comprises an antibody or fragment thereof or a cytokine.

48. The engineered cell of claim 46, wherein the recombinant polypeptide modulates the immune system of a subject.

49. The engineered cell of claim 46, wherein the recombinant polypeptide is an immune checkpoint blockade antibody.

50. The engineered cell of claim 46, wherein the recombinant polypeptide modulates tumor vasculogenesis.

51. The engineered cell of claim 46, wherein the recombinant polypeptide comprises an antibody or fragment thereof specific for TIGIT, GITR, PD-L1, PD-L2, PD-1, CTLA- 4, VISTA, CD70, TIM-3, LAG-3, CD40L, or CCR4.

52. The engineered cell of claim 47, wherein the cytokine comprises IL12, IL15 or IL18.

53. The nucleic acid of claim 50, wherein the recombinant polypeptide is specific for VEGF, VEGFR1, VEGFR2, PDGF, Ang-1, or ATI.

54. The engineered cell of claim 45, wherein the cell comprises a T cell or an NK cell.

55. The engineered cell of claim 54, wherein the T cell is T cell is CD4+, CD8+, CD3+ panT cells, or any combination thereof.

56. The engineered cell of claim 54, wherein the T cell is a mixed population of CD4+ and CD8+ T cells.

57. The engineered cell of claim 45, wherein the first chimeric antigen receptor and the second chimeric antigen receptor are expressed from a single nucleic acid construct.