Generation of antigen specific t cells

Abstract

The present invention is directed to a method of generating antigen specific T cells. Furthermore, the invention is directed to antigen specific T cells, isolated transgenic TCR's, pharmaceutical compositions containing same and their use in adoptive cell therapy. This invention in particular pertains to the use of cells co-expressing allogeneic MHC molecules and antigens to induce peptide-specific T cells from non-selected allogeneic T cell repertoires.

1 - 18 . (canceled) 
     
     
         19 . An isolated nucleic acid coding for a T cell receptor (TCR), wherein the isolated nucleic acid coding for the transgenic TCR is obtainable by a method comprising:
 (a) providing a nucleic acid encoding a patient-derived major histocompatibility complex (MHC) molecule and an antigen or a second nucleic acid encoding the antigen;   (b) co-transfecting or introducing both compounds as defined in (a) into antigen presenting cells (APCs) derived from a healthy donor;   (c) priming peripheral blood lymphocytes (PBLs) derived from the healthy donor with the APCs;   (d) selecting a T cell that is specific for the MHC-antigen ligand; and   (e) cloning the TCR of the selected T cell,   whereby an isolated nucleic acid coding for a TCR is obtained.   
     
     
         20 . A vector, which comprises the nucleic acid of  claim 19 . 
     
     
         21 . The vector of  claim 20 , which is a plasmid or a retroviral vector. 
     
     
         22 . A PBMC, which has been transformed with the vector of  claim 20 . 
     
     
         23 . A pharmaceutical composition which comprises the PBMC of  claim 22  and a pharmaceutically acceptable carrier. 
     
     
         24 . The pharmaceutical composition of  claim 23 , which is an infusion, injection or a vaccine. 
     
     
         25 - 26 . (canceled) 
     
     
         27 . The nucleic acid of  claim 19 , wherein the APCs are dendritic cells (DCs). 
     
     
         28 . A PBMC, which has been transformed with the vector of  claim 21 .