Genetic modification of T cells redirected toward CS1 enhances eradication of myeloma cells.

ABSTRACT:

Purpose

Our goal is to test whether CS1 could be targeted by chimeric antigen receptor (CAR) T cells to treat multiple myeloma (MM).

Experimental design

We generated a retroviral construct of a CS1-specific CAR and engineered primary human T cells expressing the CAR. We then tested the capacity of CS1-CAR T cells to eradicate human MM tumor cells in vitro, ex vivo, and in vivo using orthotopic MM xenograft mouse models.

Results

In vitro, compared with mock-transduced T cells, upon recognizing CS1-positive MM cells, CS1-CAR-transduced T cells secreted more IFN-γ as well as interleukin (IL)-2, expressed higher levels of the activation marker CD69, showed higher capacity for degranulation, and displayed enhanced cytotoxicity. Ectopically forced expression of CS1 in MM ce

SUBMITTER: Chu J 

PROVIDER: S-EPMC4119545 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature