Methods and materials for expanding antigen-specific t cells in culture

Abstract

This document provides methods and materials for expanding antigen-specific T cells (e.g., antigen-specific CD4 + T cells and/or antigen-specific CD8 + T cells) in culture. For example, methods and materials for performing a polyclonal stimulation step for a particular duration (e.g., from about 1 hour to about 48 hours) to increase the expansion of T cells having a desired antigen specificity are provided.

What is claimed is: 
     
         1 . A method for producing a cell population comprising T cells having specificity for an antigen of interest, wherein said method comprises:
 (a) obtaining a first cell population comprising PBMCs that were cultured in the presence of GM-CSF for a first period of time,   (b) culturing said first cell population in the presence of resiquimod,  E. coli  lipopolysaccharide, and said antigen of interest for a second period of time to form an antigen treated cell population, and   (c) culturing said antigen treated cell population in the presence of IL-7 for a third period of time to form said cell population comprising said T cells.   
     
     
         2 . The method of  claim 1 , wherein the cells of said first cell population are human cells. 
     
     
         3 . The method of  claim 1 , wherein said antigen of interest is a cancer-associated antigen. 
     
     
         4 . The method of  claim 3 , wherein said cancer-associated antigen is MUC1, HER2/neu, mesothelin, WT1, NYEso-1, MART1, gp100, or TRP, or tumor cells processed by freeze/thawing, irradiation, homogenization, or heat killing. 
     
     
         5 . The method of  claim 1 , wherein said antigen of interest is a pathogen-associated antigen. 
     
     
         6 . The method of  claim 5 , wherein said pathogen-associated antigen is a cytomegalovirus, Epstein-Barr virus, human papilloma virus,  Mycobacterium tuberculosis,  candida albicans, aspergillis,  Mycobacterium  avian intracellularis, Ebola virus, or HIV antigen. 
     
     
         7 . The method of  claim 1 , wherein said first period of time was 18 to 24 hours. 
     
     
         8 . The method of  claim 1 , wherein said second period of time is 16 to 30 hours. 
     
     
         9 . The method of  claim 1 , wherein said third period of time is 10 to 22 days.