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Modification of T Cells to Target CS1 Improves Eradication of Myeloma Cells


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CS1 is a cell surface glycoprotein that appears to be highly expressed on myeloma cells and less expressed on normal cells; CS1 overexpression has been found to promote myeloma cell growth and survival by increasing myeloma adhesion to bone marrow stromal cells and increasing myeloma colony formation. In a study reported in Clinical Cancer Research, Chu and colleagues developed chimeric antigen receptor (CAR) T cells targeting CS1 and assessed their effects on multiple myeloma tumor cells.

In response to CS1-positive myeloma cells in vitro, CS1-CAR-transduced T cells exhibited greater interferon -γ and interleukin-2 production, greater expression of the activation marker CD69, higher degranulation capacity, and increased cytotoxicity compared with mock-transduced T cells. Ectopically forced expression of CS1 in cells with low CS1 expression resulted in improved recognition and killing by CS1-CAR T cells. Similarly enhanced activities were observed with CS1-CAR T cells in ex vivo studies using primary multiple myeloma cells. Adoptive transfer of human primary T cells expressing CS1-CAR in orthotopic xenograft mouse models resulted in inhibition of human MM.1S and IM9 myeloma cells and significantly prolonged survival.

The investigators concluded, “CS1 is a promising antigen that can be targeted by CAR-expressing T cells for treatment of [multiple myeloma].” ■

Chu J, et al: Clin Cancer Res 20:3989-4000, 2014.


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