Enhanced generation of cytotoxic t-lymphocytes by il-21 mediated foxp3 suppression

Abstract

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.