Methods and compositions for chimeric antigen receptor targeting cancer cells

Abstract

The present invention provides a chimeric antigen receptor (CAR) that recognizes B7-H3 (CD276), as well as methods of use in the treatment of diseases and disorders.

1 . A chimeric antigen receptor (CAR) comprising:
 a) a signal peptide;   b) a light chain variable region comprising the amino acid sequence:   
       
         
           
                 
                 
               
                     
                   DIVMTQSHKFMSTSIGARVSITCKASQDVRTAVAWYQQKPGQ 
                 
                     
                     
                 
                     
                   SPKWYSASYRYTGVPDRFTGSGSGTDFTFTISSVQAEDLAVY 
                 
                     
                     
                 
                     
                   YCQQHYGTPPWTFGGGTKLEIK 
                 
             
                
                
                
                
                
               
            
           
         
         c) a linker peptide; 
         d) a heavy chain variable region comprising the amino acid sequence: 
       
       
         
           
                 
                 
               
                     
                   EVQLVESGGGLVKPGGSLKLSCEASRFTFSSYAMSWVRQTPE 
                 
                     
                     
                 
                     
                   KRLEWVAAISGGGRYTYYPDSMKGRFTISRDNAKNFLYLQMS 
                 
                     
                     
                 
                     
                   SLRSEDTAMYYCARHYDGYLDYWGQGTTLTVSS; 
                 
             
                
                
                
                
                
               
            
           
         
         e) a CD8α hinge polypeptide; 
         f) a CD8α transmembrane domain; 
         g) a 4-1BB costimulatory domain; and 
         h) a CD3ζ signaling domain. 
       
     
     
         2 . A chimeric antigen receptor (CAR) comprising:
 a) a signal peptide;   b) a light chain variable region comprising the amino acid sequence:   
       
         
           
                 
                 
               
                     
                   DIVMTQSHKFMSTSIGARVSITCKASQDVRTAVAWYQQKPGQSP 
                 
                     
                     
                 
                     
                   KWYSASYRYTGVPDRFTGSGSGTDFTFTISSVQAEDLAVYYCQQ 
                 
                     
                     
                 
                     
                   HYGTPPWTFGGGTKLEIK 
                 
             
                
                
                
                
                
               
            
           
         
         c) a linker peptide; 
         d) a heavy chain variable region comprising the amino acid sequence: 
       
       
         
           
                 
                 
               
                     
                   EVQLVESGGGLVKPGGSLKLSCEASRFTFSSYAMSWVRQTPEKR 
                 
                     
                     
                 
                     
                   LEWVAAISGGGRYTYYPDSMKGRFTISRDNAKNFLYLQMSSLRS 
                 
                     
                     
                 
                     
                   EDTAMYYCARHYDGYLDYWGQGTTLTVSS; 
                 
             
                
                
                
                
                
               
            
           
         
         e) a CD8α hinge polypeptide; 
         f) a CD8α transmembrane domain; 
         g) a CD28 costimulatory domain; and 
         h) a CD3ζ signaling domain. 
       
     
     
         3 . A cell that expresses the CAR of  claim 1 . 
     
     
         4 . The cell of  claim 3 , wherein the cell is selected from the group consisting of a αβT cell, a natural killer (NK) cell, a cytotoxic T lymphocyte (CTL), a regulatory T cell, a natural killer T (NKT) cell, a Th17 cell, and a γδT cell. 
     
     
         5 . The cell of  claim 4 , wherein the cell is an autologous cell. 
     
     
         6 . A composition comprising the cell of  claim 4 . 
     
     
         7 . A polynucleotide encoding the CAR of  claim 1 . 
     
     
         8 . A cell comprising the polynucleotide of  claim 7 . 
     
     
         9 . The cell of  claim 8 , wherein the cell is selected from the group consisting of a αβT cell, a natural killer (NK) cell, a cytotoxic T lymphocyte (CTL), a regulatory T cell, a natural killer T (NKT) cell, a Th17 cell, and a γδT cell. 
     
     
         10 . The cell of  claim 9 , wherein the cell is an autologous cell. 
     
     
         11 . A composition comprising the cell of  claim 9 . 
     
     
         12 . A retroviral vector comprising the polynucleotide of  claim 7 . 
     
     
         13 . A cell comprising the retroviral vector of  claim 12 . 
     
     
         14 . The cell of  claim 13 , wherein the cell is selected from the group consisting of a αδT cell, a natural killer (NK) cell, a cytotoxic T lymphocyte (CTL), a regulatory T cell, a natural killer T (NKT) cell, a Th17 cell, and a γδT cell. 
     
     
         15 . The cell of  claim 14 , wherein the cell is an autologous cell. 
     
     
         16 . A composition comprising the cell of  claim 14 . 
     
     
         17 . A cell that expresses the CAR of  claim 2 . 
     
     
         18 . The cell of  claim 17 , wherein the cell is selected from the group consisting of a αδT cell, a natural killer (NK) cell, a cytotoxic T lymphocyte (CTL), a regulatory T cell, a natural killer T (NKT) cell, a Th17 cell, and a γδT cell. 
     
     
         19 . The cell of  claim 18 , wherein the cell is an autologous cell. 
     
     
         20 . A composition comprising the cell of  claim 18 . 
     
     
         21 .- 30 . (canceled)