Methods of using il-21 for adoptive immunotherapy and identification of tumor antigens

Abstract

Methods for preparing ex vivo T cell cultures using IL-21 compositions for use in adoptive immunotherapy are described. Addition of IL-21 to cultures of non-terminally differentiated T cells population, either isolated or present in peripheral blood mononuclear cells are exposed to one or more tumor antigens, and in the presence of IL-21 compositions and antigen presenting cells (APCs), the resulting T cell population has an enhanced antigen-specificity; and can be reintroduced into the patient. Methods are also disclosed for identifying tumor antigens by culturing T cell populations exposed to IL-21 compositions and APCs in the presence of tumor material.

1 . A method of preparing a T cell population comprising:
 obtaining the T cell population from PBMCs,   activating the obtained T cell population,   transducing the activated T cell population with a viral vector comprising a nucleic acid encoding a protein,   expanding the transduced T cell population, and
 wherein the transducing is performed in the presence of IL-21. 
   
     
     
         2 . The method of  claim 1 , wherein the PBMCs are obtained from a patient or a healthy donor. 
     
     
         3 . The method of  claim 1 , wherein the transducing is further performed in the presence of at least one cytokine selected from IL-2, IL-12, and IL-15. 
     
     
         4 . The method of  claim 1 , wherein the protein is a T cell receptor. 
     
     
         5 . The method of  claim 1 , further comprising restimulating the expanded transduced T cell population in the presence of a feeder cell and an anti-CD3 antibody. 
     
     
         6 . The method of  claim 5 , wherein the feeder cell is an irradiated allogenic feeder cell. 
     
     
         7 . The method of  claim 6 , wherein the feeder cell comprises a PBL and an LCL. 
     
     
         8 . The method of  claim 7 , further comprising culturing the restimulated cells in the presence of IL-2. 
     
     
         9 . A method of preparing a T cell population comprising:
 obtaining the T cell population from PBMCs,   activating the obtained T cell population,   transducing the activated T cell population with a viral vector comprising a nucleic acid encoding a protein,   expanding the transduced T cell population, and
 wherein the activating and the transducing are performed in the presence of IL-21. 
   
     
     
         10 . The method of  claim 9 , wherein the PBMCs are obtained from a patient or a healthy donor. 
     
     
         11 . The method of  claim 9 , wherein the activating and the transducing are further performed in the presence of at least one cytokine selected from IL-2, IL-12, and IL-15. 
     
     
         12 . The method of  claim 9 , wherein the protein is a T cell receptor. 
     
     
         13 . The method of  claim 9 , further comprising restimulating the expanded transduced T cell population in the presence of a feeder cell and an anti-CD3 antibody. 
     
     
         14 . The method of  claim 13 , wherein the feeder cell is an irradiated allogenic feeder cell. 
     
     
         15 . A method of preparing a T cell population comprising:
 obtaining the T cell population from PBMCs,   activating the obtained T cell population,   transducing the activated T cell population with a viral vector comprising a nucleic acid encoding a protein,   expanding the transduced T cell population, and
 wherein the transducing and the expanding are performed in the presence of IL-21. 
   
     
     
         16 . The method of  claim 15 , wherein the PBMCs are obtained from a patient or a healthy donor. 
     
     
         17 . The method of  claim 15 , wherein the transducing and the expanding are further performed in the presence of at least one cytokine selected from IL-2, IL-12, and IL-15. 
     
     
         18 . The method of  claim 15 , wherein the protein is a T cell receptor. 
     
     
         19 . The method of  claim 15 , further comprising restimulating the expanded transduced T cell population in the presence of a feeder cell and an anti-CD3 antibody. 
     
     
         20 . The method of  claim 19 , wherein the feeder cell is an irradiated allogenic feeder cell.