CS1-CTLA-4 CAR T cells

CS1-CTLA-4 CAR T cells are a novel chimeric antigen receptor (CAR) T cell therapy designed for the treatment of multiple myeloma (MM). This therapy targets CS1 (also known as SLAMF7), a cell surface glycoprotein highly expressed on MM cells. Unlike previous CS1-targeted CAR T cells that used a 4-1BB costimulatory domain, this refined design incorporates the cytotoxic T-lymphocyte antigen 4 (CTLA-4) signaling domain. The CTLA-4 domain aims to reduce severe cytokine-related toxicity by dampening T cell activation and decreasing the production of pro-inflammatory cytokines such as IFN-γ, IL-2, and TNF-α, while preserving anti-tumor activity. The intracellular domain of CTLA-4 achieves this by recruiting phosphatases like PTP1B, which attenuates T cell receptor and CAR signaling, and PP2A, which reduces cytokine release. Preclinical studies have shown that CS1-CTLA-4 CAR T cells exhibit lower activation and cytokine secretion but maintain cytotoxic activity against MM cells, suggesting a potentially safer therapeutic profile.