Jianhong Chu 1 , 2 , Youcai Deng 1 , 3 , Don M. Benson Jr 1 , 2 , Shun He 2 , Tiffany Hughes 2 , Jianying Zhang 4 , Yong Peng 2 , Hsiaoyin Mao 2 , Ling Yi 2 , Kalpana Ghoshal 2 , 5 , Xiaoming He 2 , 6 , Steven M. Devine 1 , 2 , 7 , Xiaoliu Zhang 8 , Michael A. Caligiuri 1 , 2 , Craig C. Hofmeister 1 , 2 , Jianhua Yu 1 , 2 , 7
26 September 2013
Multiple myeloma (MM) is an incurable hematological malignancy. Chimeric antigen receptor (CAR)-expressing T cells have been demonstrated successful in the clinic to treat B-lymphoid malignancies. However, the potential utility of antigen-specific CAR-engineered natural killer (NK) cells to treat MM has not been explored. In this study, we determined whether CS1, a surface protein that is highly expressed on MM cells, can be targeted by CAR NK cells to treat MM. We successfully generated a viral construct of a CS1-specific CAR and expressed it in human NK cells. In vitro, CS1-CAR NK cells displayed enhanced MM cytolysis and IFN-γ production, and showed a specific CS1-dependent recognition of MM cells. Ex vivo, CS1-CAR NK cells also showed similarly enhanced activities when responding to primary MM tumor cells. More importantly, in an aggressive orthotopic MM xenograft mouse model, adoptive transfer of NK-92 cells expressing CS1-CAR efficiently suppressed the growth of human IM9 MM cells and also significantly prolonged mouse survival. Thus, CS1 represents a viable target for CAR-expressing immune cells, and autologous or allogeneic transplantation of CS1-specific CAR NK cells may be a promising strategy to treat MM.