Methods of treating Epstein-Barr virus-associated lymphoproliferative disorders by T cell therapy

1. A method of treating an EBV-LPD (Epstein-Barr Virus-associated lymphoproliferative disorder) in a human patient comprising administering to the human patient a population of allogeneic T cells comprising EBV-specific T cells; wherein the EBV-LPD is a disorder of cells of B cell lineage, wherein the human patient has failed a combination chemotherapy to treat the EBV-LPD and a therapy with an anti-CD20 monoclonal antibody to treat the EBV-LPD, and wherein the population of allogeneic T cells is restricted by an human leukocyte antigen (HLA) allele shared with cells of the EBV-LPD.

2. The method of claim 1 , wherein the human patient also has failed a radiation therapy to treat the EBV-LPD.

3. The method of claim 1 , wherein the EBV-LPD is an EBV-positive lymphoma.

4. The method of claim 1 , wherein the EBV-LPD is present in the central nervous system of the human patient.

5. The method of claim 1 , wherein the human patient has been the recipient of a solid organ transplant from a transplant donor.

6. The method of claim 1 , wherein the human patient has been the recipient of a hematopoietic stem cell transplant from a transplant donor.

7. The method of claim 5 , wherein the population of allogeneic T cells is derived from a donor other than the transplant donor.

8. 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 EBV-specific T cells; wherein the second population of allogeneic T cells is restricted by a different HLA allele shared with cells of the EBV-LPD.

9. The method of claim 1 , wherein the EBV-LPD is diffuse large B-cell lymphoma.

10. The method of claim 1 , wherein the human patient is infected with HIV.

11. The method of claim 2 , wherein the EBV-LPD is an EBV-positive lymphoma.

12. The method of claim 2 , wherein the EBV-LPD is present in the central nervous system of the human patient.

13. The method of claim 2 , wherein the human patient has been the recipient of a solid organ transplant from a transplant donor.

14. The method of claim 2 , wherein the human patient has been the recipient of a hematopoietic stem cell transplant from a transplant donor.

15. The method of claim 13 , wherein the population of allogeneic T cells is derived from a donor other than the transplant donor.

16. 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 EBV-specific T cells; wherein the second population of allogeneic T cells is restricted by a different HLA allele shared with cells of the EBV-LPD.

17. The method of claim 2 , wherein the EBV-LPD is diffuse large B-cell lymphoma.

18. The method of claim 2 , wherein the human patient is infected with HIV.

19. The method of claim 6 , wherein the population of allogeneic T cells is derived from a donor other than the transplant donor.

20. The method of claim 14 , wherein the population of allogeneic T cells is derived from a donor other than the transplant donor.

21. The method of claim 1 , wherein the EBV-LPD is resistant to the combination chemotherapy to treat the EBV-LPD and is resistant to the therapy with the anti-CD20 monoclonal antibody to treat the EBV-LPD.

22. The method of claim 2 , wherein the EBV-LPD is resistant to the radiation therapy to treat the EBV-LPD.

23. The method of claim 1 , wherein the anti-CD20 monoclonal antibody is rituximab.

24. The method of claim 2 , wherein the anti-CD20 monoclonal antibody is rituximab.

25. A method of treating an EBV-LPD in a human patient comprising administering to the human patient a population of allogeneic T cells comprising EBV-specific T cells; wherein the EBV-LPD is diffuse large B-cell lymphoma, wherein the human patient has failed a combination chemotherapy to treat the EBV-LPD, and wherein the population of allogeneic T cells is restricted by an HLA allele shared with cells of the EBV-LPD.

26. The method of claim 25 , wherein the EBV-LPD is resistant to the combination chemotherapy to treat the EBV-LPD.

27. The method of claim 25 , wherein the human patient also has failed a radiation therapy to treat the EBV-LPD.

28. The method of claim 27 , wherein the EBV-LPD is resistant to the radiation therapy to treat the EBV-LPD.

29. The method of claim 25 , wherein the EBV-LPD is present in the central nervous system of the human patient.

30. The method of claim 25 , wherein the human patient has been the recipient of a solid organ transplant from a transplant donor.

31. The method of claim 25 , wherein the human patient has been the recipient of a hematopoietic stem cell transplant from a transplant donor.

32. The method of claim 30 , wherein the population of allogeneic T cells is derived from a donor other than the transplant donor.

33. The method of claim 31 , wherein the population of allogeneic T cells is derived from a donor other than the transplant donor.

34. The method of claim 25 , wherein the human patient is infected with HIV.

35. The method of claim 25 , 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 EBV-specific T cells; wherein the second population of allogeneic T cells is restricted by a different HLA allele shared with cells of the EBV-LPD.

36. The method of claim 1 , wherein the population of allogeneic T cells is generated in vitro by sensitizing allogeneic T cells to one or more EBV antigens using EBV-transformed B cells.

37. The method of claim 25 , wherein the population of allogeneic T cells is generated in vitro by sensitizing allogeneic T cells to one or more EBV antigens using EBV-transformed B cells.