Methods of treating CMV retinitis by T cell therapy
Methods of treating CMV (cytomegalovirus) retinitis in a human patient in need thereof, comprising administering to the human patient a population of allogeneic T cells comprising CMV-specific T cells, wherein the human patient is infected with human immunodeficiency virus (HIV) or has been the recipient of a solid organ transplant.
1. A method of treating CMV (cytomegalovirus) retinitis in a human patient in need thereof, comprising administering to the human patient a population of allogeneic T cells comprising CMV-specific T cells; wherein the human patient is infected with HIV, wherein the CMV-specific T cells recognize CMVpp65, and wherein the population of allogeneic T cells is restricted by an HLA allele shared with at least some, optionally all, of the CMV-infected cells.
2. A method of treating CMV retinitis in a human patient in need thereof, comprising administering to the human patient a population of allogeneic T cells comprising CMV-specific T cells; wherein the human patient has been the recipient of a solid organ transplant from a transplant donor, wherein the CMV-specific T cells recognize CMVpp65, and wherein the population of allogeneic T cells is restricted by an HLA allele shared with at least some, optionally all, of the CMV-infected cells.
3. The method of claim 2 , wherein the solid organ transplant is a kidney transplant, a liver transplant, a heart transplant, an intestinal transplant, a pancreas transplant, a lung transplant, a small bowel transplant, or a combination thereof.
4. The method of claim 1 , which further comprises prior to said administering step a step of generating the population of allogeneic T cells in vitro.
5. The method of claim 4 , wherein the step of generating the population of allogeneic T cells in vitro comprises sensitizing allogeneic T cells to CMVpp65.
6. The method of claim 1 , wherein the administering is by infusion of the population of allogeneic T cells.
7. The method of claim 1 , further comprising, after administering to the human patient the population of allogeneic T cells, administering to the human patient a second population of allogeneic T cells comprising CMV-specific T cells that recognize CMVpp65; wherein the second population of allogeneic T cells is restricted by a different HLA allele shared with at least some, optionally all, of the CMV-infected cells.
8. The method of claim 1 , wherein the human patient has failed a previous therapy to treat the CMV retinitis.
9. The method of claim 8 , wherein the previous therapy is treatment with at least one anti-viral agent.
10. The method of claim 9 , wherein the at least one anti-viral agent is selected from the group consisting of ganciclovir, foscarnet, valganciclovir, cidofovir, leflunomide, and combinations thereof.
11. The method of claim 1 , wherein the population of allogeneic T cells has not been transduced ex vivo with a gene that encodes a CMV-specific T-cell receptor.
12. The method of claim 1 , wherein at least some, optionally all, of the cells of the population of allogeneic T cells are rapamycin-sensitive.
13. The method of claim 1 , wherein the population of allogeneic T cells is not administered in combination with a PD-1 antagonist.
14. The method of claim 1 , wherein the human patient has not been the recipient of a hematopoietic stem cell transplant.
15. The method of claim 1 , wherein the human patient has an active, not latent, CMV infection.
16. The method of claim 1 , wherein a CMV in the human patient has at least one mutation in its genome that confers resistance to one or more anti-viral agents.
17. The method of claim 16 , wherein the one or more anti-viral agents are selected from the group consisting of ganciclovir, foscarnet, valganciclovir, cidofovir, leflunomide, and combinations thereof.
18. The method of claim 16 , wherein the at least one mutation is a mutation in the UL97 gene, a mutation in the UL54 gene, or a first mutation in the UL97 gene and a second mutation in the UL54 gene.
19. The method of claim 16 , which further comprises prior to said administering step a step of genotyping a CMV of the human patient.
20. The method of claim 2 , wherein the population of allogeneic T cells has not been transduced ex vivo with a gene that encodes a CMV-specific T-cell receptor.
21. The method of claim 2 , wherein at least some, optionally all, of the cells of the population of allogeneic T cells are rapamycin-sensitive.
22. The method of claim 2 , wherein the population of allogeneic T cells is not administered in combination with a PD-1 antagonist.
23. The method of claim 2 , wherein the human patient has not been the recipient of a hematopoietic stem cell transplant.
24. The method of claim 2 , wherein the human patient has an active, not latent, CMV infection.
25. The method of claim 1 , wherein the administering is by intravenous infusion of the population of allogeneic T cells.
26. The method of claim 2 , wherein the administering is by intravenous infusion of the population of allogeneic T cells.
27. The method of claim 11 , wherein the administering is by intravenous infusion of the population of allogeneic T cells.
28. The method of claim 12 , wherein the administering is by intravenous infusion of the population of allogeneic T cells.
29. The method of claim 13 , wherein the administering is by intravenous infusion of the population of allogeneic T cells.
30. The method of claim 14 , wherein the administering is by intravenous infusion of the population of allogeneic T cells.
31. The method of claim 15 , wherein the administering is by intravenous infusion of the population of allogeneic T cells.
32. The method of claim 20 , wherein the administering is by intravenous infusion of the population of allogeneic T cells.
33. The method of claim 21 , wherein the administering is by intravenous infusion of the population of allogeneic T cells.
34. The method of claim 22 , wherein the administering is by intravenous infusion of the population of allogeneic T cells.
35. The method of claim 23 , wherein the administering is by intravenous infusion of the population of allogeneic T cells.
36. The method of claim 24 , wherein the administering is by intravenous infusion of the population of allogeneic T cells.
37. The method of claim 1 , wherein: (a) the population of allogeneic T cells has not been transduced ex vivo with a gene that encodes a CMV-specific T-cell receptor; (b) at least some, optionally all, of the cells of the population of allogeneic T cells are rapamycin-sensitive; (c) the population of allogeneic T cells is not administered in combination with a PD-1 antagonist; (d) the human patient has not been the recipient of a hematopoietic stem cell transplant; (e) the human patient has an active, not latent, CMV infection; and (f) the administering is by intravenous infusion of the population of allogeneic T cells.
38. The method of claim 2 , wherein: (a) the population of allogeneic T cells has not been transduced ex vivo with a gene that encodes a CMV-specific T-cell receptor; (b) at least some, optionally all, of the cells of the population of allogeneic T cells are rapamycin-sensitive; (c) the population of allogeneic T cells is not administered in combination with a PD-1 antagonist; (d) the human patient has not been the recipient of a hematopoietic stem cell transplant; (e) the human patient has an active, not latent, CMV infection; and (f) the administering is by intravenous infusion of the population of allogeneic T cells.
39. The method of claim 8 , wherein the CMV retinitis is resistant to the previous therapy.
40. The method of claim 39 , wherein the previous therapy is treatment with at least one anti-viral agent.
41. The method of claim 2 , wherein the population of allogeneic T cells is derived from a donor other than the transplant donor.
42. The method of claim 2 , which further comprises prior to said administering step a step of generating the population of allogeneic T cells in vitro.
43. The method of claim 42 , wherein the step of generating the population of allogeneic T cells in vitro comprises sensitizing allogeneic T cells to CMVpp65.
44. The method of claim 2 , wherein the administering is by infusion of the population of allogeneic T cells.
45. The method of claim 2 , further comprising, after administering to the human patient the population of allogeneic T cells, administering to the human patient a second population of allogeneic T cells comprising CMV-specific T cells that recognize CMVpp65; wherein the second population of allogeneic T cells is restricted by a different HLA allele shared with at least some, optionally all, of the CMV-infected cells.
46. The method of claim 2 , wherein the human patient has failed a previous therapy to treat the CMV retinitis.
47. The method of claim 46 , wherein the CMV retinitis is resistant to the previous therapy.
48. The method of claim 47 , wherein the previous therapy is treatment with at least one anti-viral agent.
49. The method of claim 46 , wherein the previous therapy is treatment with at least one anti-viral agent.
50. The method of claim 49 , wherein the at least one anti-viral agent is selected from the group consisting of ganciclovir, foscarnet, valganciclovir, cidofovir, leflunomide, and combinations thereof.
51. The method of claim 2 , wherein a CMV in the human patient has at least one mutation in its genome that confers resistance to one or more anti-viral agents.
52. The method of claim 51 , wherein the one or more anti-viral agents are selected from the group consisting of ganciclovir, foscarnet, valganciclovir, cidofovir, leflunomide, and combinations thereof.
53. The method of claim 51 , wherein the at least one mutation is a mutation in the UL97 gene, a mutation in the UL54 gene, or a first mutation in the UL97 gene and a second mutation in the UL54 gene.
54. The method of claim 51 , which further comprises prior to said administering step a step of genotyping a CMV of the human patient.