NCIt definition : 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.;