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

AI Article Synopsis

  • The study aims to evaluate the effectiveness of targeting CS1 antigen using CAR T cells as a treatment for multiple myeloma (MM).
  • Researchers engineered T cells with a CS1-specific CAR and tested their ability to kill MM tumor cells in various settings, including laboratory cultures and mouse models.
  • Results showed that CS1-CAR T cells outperformed regular T cells in recognizing and destroying CS1-positive MM cells, leading to significant tumor suppression and improved survival in mice.

Article 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 cells with low CS1 expression enhanced recognition and killing by CAR T cells. Ex vivo, CS1-CAR T cells also showed similarly enhanced activities when responding to primary MM cells. More importantly, in orthotopic MM xenograft mouse models, adoptive transfer of human primary T cells expressing CS1-CAR efficiently suppressed the growth of human MM.1S and IM9 myeloma cells and significantly prolonged mouse survival.

Conclusions: CS1 is a promising antigen that can be targeted by CAR-expressing T cells for treatment of MM.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4119545PMC
http://dx.doi.org/10.1158/1078-0432.CCR-13-2510DOI Listing

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