Journal
LEUKEMIA
Volume 28, Issue 4, Pages 917-927Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/leu.2013.279
Keywords
CS1; chimeric antigen receptor; NK cells; multiple myeloma
Categories
Funding
- Multiple Myeloma Opportunities for Research and Education (MMORE)
- National Institutes of Health [CA155521, 1R41OD018403, CA095426, CA068458]
- National Blood Foundation
- American Cancer Society [IRG-67-003-47]
- Ohio State University Comprehensive Cancer Center Pelotonia grant
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Multiple myeloma (MM) is an incurable hematological malignancy. Chimeric antigen receptor (CAR)-expressing T cells have been demonstrated successfully 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 interferon-gamma (IFN-gamma) 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.
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