abstract |
A genetically modified cytotoxic T cell includes one or more exogenous nucleic acid molecules encoding a transgenic antigen-targeting construct. Estrogen receptor-binding fragment-associated antigen 9 (EBAG9) activity is inhibited in the cells. The antigen-targeting construct can be a chimeric antigen receptor (CAR) or T cell receptor (TCR). The modified T cell can be used in the treatment of a proliferative disease, in particular for the treatment of hematologic malignancies. A pharmaceutical composition includes the modified T cell, a nucleic acid vector encoding the antigen-targeting construct and an inhibitor of EBAG9, such an RNA interference molecule. An in vitro method can increase the cytolytic activity of a cytotoxic T cell. |