B7-H6–NKp46 therapeutic axis (B7-H6/NKp46)

The B7-H6–NKp46 therapeutic axis is a synthetic immune interaction utilized in cancer immunotherapy to redirect Natural Killer (NK) cells against tumor cells. B7-H6 (also known as NCR3LG1) is a member of the B7 family that is selectively expressed on the surface of various tumor cells, including lymphomas, melanomas, and carcinomas, but is largely absent from healthy tissues. While B7-H6 is the natural ligand for the NKp30 (NCR3) receptor, therapeutic strategies employ bispecific or multispecific NK cell engagers (NKCEs) to bridge B7-H6 on tumor cells with the NKp46 (NCR1) activating receptor on NK cells. This engagement triggers NK cell activation, leading to the release of cytotoxic granules such as perforin and granzymes, as well as proinflammatory cytokines like IFN-gamma and TNF-alpha, resulting in targeted tumor cell destruction. This axis is currently being explored in various clinical and preclinical programs, particularly for solid tumors and hematological malignancies where B7-H6 is overexpressed as a stress-induced ligand.

Other names

NCR3LG1-NCR1 axisB7H6-NKp46 engagerNKp46-B7H6 bispecificB7-H6/NKp46 interactionNKp46 ligand B7H6

Redirection of Natural Killer (NK) cells to B7-H6-expressing tumor cells by simultaneously binding the tumor-associated antigen B7-H6 and the NK cell activating receptor NKp46 (often in combination with CD16a), facilitating the formation of an immunological synapse and triggering NK cell-mediated cytotoxicity.