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

Get Permission

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.




By continuing to browse this site you permit us and our partners to place identification cookies on your browser and agree to our use of cookies to identify you for marketing. Read our Privacy Policy to learn more.