ENHANCED GENERATION OF CYTOTOXIC T-LYMPHOCYTES BY IL-21 MEDIATED FOXP3 SUPPRESSION
A method of carrying out adoptive immunotherapy by administering a subject an antigen-specific cytotoxic T lymphocytes (CTL) preparation in a treatment-effective amount is described. In the method, the CTL preparation is preferably administered as a preparation of an in vitro antigen-stimulated and expanded primate CTL population, the CTL population: (i) depleted of FoxP3+T lymphocytes prior to antigen stimulation; (ii) antigen-stimulated in vitro in the presence of interleukin-21; or (iii) both depleted of FoxP3+T lymphocytes prior to antigen stimulation and then antigen-stimulated in vitro in the presence of interleukin-21. Methods of preparing such compositions, and compositions useful for carrying out the adoptive immunotherapy, are also described.
1 .- 16 . (canceled)
17 . A pharmaceutical formulation comprising a single T cell population, wherein the T cell population consists of at least 10 9 CD8 + CD25 − antigen-specific human cytotoxic T lymphocyte (CTL) cells.
18 . The pharmaceutical formulation of claim 17 , wherein the antigen is a tumor antigen.
19 . The pharmaceutical formulation of claim 18 , wherein the tumor antigen is NY-ESO-1.
20 . The pharmaceutical formulation of claim 18 , wherein the tumor antigen is MART-1.
21 . The pharmaceutical formulation of claim 18 , wherein the tumor antigen is gp100.
22 . The pharmaceutical formulation of claim 17 , wherein the antigen is a microbe-associated antigen.
23 . The pharmaceutical formulation of claim 17 , wherein the antigen-specific human CTL cells comprise a transgene.
24 . The pharmaceutical formulation of claim 17 , further comprising a pharmaceutically acceptable carrier.
25 . The pharmaceutical formulation of claim 17 , wherein the T cell population consists of at least 10 10 CD8 + CD25 − antigen-specific human CTL cells.
26 . The pharmaceutical formulation of claim 17 , wherein the antigen-specific human CTL cells are CD28 + CCR7 − .
27 . A method for treating a patient who has cancer that presents a tumor antigen, the method comprising administering to the patient the pharmaceutical formulation of claim 17 , wherein the antigen-specific human CTL cells are specific for the tumor antigen.
28 . A method for treating a patient who has cancer that presents a tumor antigen, the method comprising administering to the patient a pharmaceutical formulation comprising a single T cell population, wherein the T cell population consists of at least 10 9 CD8 + CD25 − antigen-specific human CTL cells, wherein the antigen-specific human CTL cells are specific for the tumor antigen.
29 . The method of claim 28 , wherein the antigen-specific human CTL cells comprise a transgene.
30 . The method of claim 28 , wherein the pharmaceutical formulation further comprises a pharmaceutically acceptable carrier.
31 . The method of claim 28 , wherein the T cell population consists of at least 10 10 CD8 + CD25 − antigen-specific human CTL cells.
32 . The method of claim 28 , wherein the antigen-specific human CTL cells are CD28 + CCR7 − .
33 . The method of claim 28 , wherein the tumor antigen is NY-ESO-1.
34 . The method of claim 28 , wherein the tumor antigen is MART-1.
35 . The method of claim 28 , wherein the tumor antigen is gp100.