autologous TIM-4 chimeric engulfment receptor T cells CER-1236

A preparation of autologous T cells genetically engineered to express a chimeric engulfment receptor (CER) that contains the phosphatidylserine (PS) receptor T-cell immunoglobulin and mucin domain-containing protein 4 (TIM-4) extracellular signaling domain linked to the transmembrane domain of the co-stimulatory signaling protein CD28 and the zeta chain of the TCR/CD3 complex (CD3-zeta) fused to the Toll/interleukin-1 receptor (TIR) domain from Toll-like receptor 2 (TLR-2; TLR2; Toll/Interleukin 1 Receptor-Like 4) (TLR2-TIR) as an additional innate signaling domain to enhance antigen-presenting cell (APC)-function, with potential phagocytic, immunomodulating and antineoplastic activities. Upon administration, autologous TIM-4 CER T cells CER-1236 target and bind to the phospholipid and TIM-4 ligand (TIM-4-L) phosphatidylserine expressed on tumor cells. This binding induces cytolytic and phagocyte-like engulfment activity of the CER T cells, thereby killing TIM-4-L expressing tumor cells. Activation of the T-cell signaling domains activate and enhance the cytotoxic T-lymphocyte response against the tumor cells, thereby further killing tumor cells. In addition, the tumor-associated antigens (TAAs) that are leaked from the tumor cells are taken up by CER-1236 and are processed and presented to the immune system through an APC-like presentation, thereby inducing secondary immune responses and activating bystander T cells. Aberrant TIM-4-L expression is observed on malignant cells of multiple lineages, but its expression is minimal on normal, healthy cells.