Tim4 ligand (phosphatidylserine displayed on tumor cell surface)

Class

Chimeric engulfment receptor (CER) T-cell therapy (autologous, phagocytic)

Phosphatidylserine (PS) is a lipid that normally sits on the inner face of a healthy cell's outer membrane, kept there by enzymes called flippases. When a cell dies, becomes stressed, or turns malignant, this asymmetry breaks down and PS appears on the outer surface, functioning as an "eat-me" signal. In normal physiology, immune cells such as macrophages recognize surface PS through receptors including TIM4 and then engulf, or phagocytose, the marked cell, a process called efferocytosis. This engineered cell therapy repurposes that recognition system: T cells are modified to carry a chimeric engulfment receptor built around the PS-binding portion of TIM4, fused to signaling machinery that drives the T cell to engulf the bound target rather than kill it through conventional cytotoxic mechanisms. Because PS exposure is a common feature across many tumor types, independent of any single mutated protein, this approach can in principle address tumors regardless of the specific antigens they carry, potentially offering broader applicability than therapies that depend on one defined tumor marker. It is being explored in oncology as an alternative or complement to antigen-restricted engineered T-cell approaches, particularly where tumor heterogeneity limits conventional targeting.