B7-H6 (NCR3LG1) x CD3

Class

Bispecific T-cell engager (TcE) antibody

Pathway

T-cell redirection to B7-H6-expressing tumor cells via simultaneous CD3/B7-H6 binding

B7-H6 (also called NCR3LG1) is a cell-surface protein that is largely absent from healthy tissue but becomes displayed on the surface of many tumor cells, where it normally serves as a signal recognized by natural killer cells through the receptor NKp30. Because its expression is largely restricted to stressed or malignant cells, it offers a relatively tumor-selective marker that can be exploited therapeutically. A bispecific T-cell engager pairs a binding arm for B7-H6 with a second arm for CD3, a signaling component of the T-cell receptor complex present on essentially all T cells. By binding both simultaneously, the antibody physically bridges a T cell to a tumor cell, forming an artificial immune synapse that triggers the T cell to release cytotoxic granules and kill the tumor cell, regardless of whether that T cell's native receptor would have recognized the tumor at all. This redirection strategy sidesteps the need for tumor-specific antigen recognition by the T-cell receptor itself and instead relies on the engineered bispecific molecule to do the targeting. Such engagers are studied broadly across solid and hematologic malignancies that display the relevant surface marker, with the underlying rationale being to harness the cytotoxic potential of a patient's own T-cell pool against tumors that might otherwise evade immune surveillance.