Modified cells and methods of therapy

Abstract

Genetically modified compositions, such as non-viral vectors and T cells, for treating cancer are disclosed. Also disclosed are the methods of making and using the genetically modified compositions in treating cancer.

1 - 30 . (canceled) 
     
     
         31 . An in vitro composition that comprises:
 a genetically engineered human stem cell, or human progenitor cell that comprises:   a genomic disruption in an endogenous cytokine inducible SH2-containing (CISH) gene that suppresses or eliminates expression of a cytokine inducible SH2-containing (CISH) protein encoded by said CISH gene in said stem cell or progenitor cell.   
     
     
         32 . The in vitro composition of  claim 31 , wherein said genomic disruption is a nucleotide insertion or deletion in said CISH gene. 
     
     
         33 . The in vitro composition of  claim 31 , wherein said genomic disruption is located within 20 bases immediately 5′ of a first nucleotide of a protospacer adjacent motif (PAM) sequence in said CISH gene. 
     
     
         34 . The in vitro composition of  claim 31 , wherein said genomic disruption is in exon 2 or exon 3 of the CISH gene. 
     
     
         35 . The in vitro composition of  claim 31 , wherein said genomic disruption is a targeted double strand break in the CISH gene. 
     
     
         36 . The in vitro composition of  claim 31 , wherein said composition comprises human stem cells. 
     
     
         37 . A pharmaceutical composition that comprises a population of the genetically engineered human stem cell, or human progenitor cell of the in vitro composition of claim  30 , or cells differentiated therefrom, and a pharmaceutically acceptable carrier. 
     
     
         38 . A method for treating a disease in a human subject in need thereof, the method comprising administering the pharmaceutical composition of  claim 37  to the human subject. 
     
     
         39 . A method for treating a disease in a human subject in need thereof, the method comprising:
 administering to said human subject an effective amount of a pharmaceutical composition that comprises a population of ex vivo engineered human cells comprising stem cells, progenitor cell or cells differentiated therefrom, that comprise a genomic disruption in an endogenous cytokine inducible SH2-containing (CISH) gene that suppresses or eliminates expression of a cytokine inducible SH2-containing (CISH) protein encoded by said CISH gene in said stem cells, progenitor cell or cells differentiated therefrom; and   a pharmaceutically acceptable carrier or excipient.   
     
     
         40 . The method of  claim 39 , wherein the ex vivo engineered human cells further comprise an exogenous T cell receptor (TCR) or chimeric antigen receptor (CAR). 
     
     
         41 . The method of  claim 39 , wherein said ex vivo engineered human cells are autologous to said human subject. 
     
     
         42 . The method of  claim 39 , further comprising administering to said human subject a preparatory regimen that transiently depletes host lymphocytes in said subject prior to administering said pharmaceutical composition. 
     
     
         43 . The method of  claim 42 , wherein said preparatory regimen comprises cyclophosphamide, fludarabine, or a combination thereof. 
     
     
         44 . The method of  claim 39 , wherein said cells differentiated from said stem cells or progenitor cells comprise dendritic cells, macrophages or combination thereof. 
     
     
         45 . The method of  claim 39 , wherein said genomic disruption is in exon 2 or exon 3 of the CISH gene. 
     
     
         46 . The method of  claim 39 , wherein said genomic disruption comprises a double strand break in said CISH gene. 
     
     
         47 . The method of  claim 39 , wherein said ex vivo engineered human cells further comprise a genomic disruption in an endogenous transforming growth factor beta receptor II (TGFBRII) gene.