Natural cytotoxicity trigger receptor 1 (NKp46) (NKp46)

Natural cytotoxicity trigger receptor 1 (NCR1), commonly known as NKp46 or CD335, is a type I transmembrane protein and a key activating receptor expressed almost exclusively on Natural Killer (NK) cells and a subset of innate lymphoid cells (UniProt P14778). As a member of the immunoglobulin superfamily, NKp46 plays a fundamental role in the innate immune system by recognizing a diverse array of ligands, including viral hemagglutinins, bacterial surface proteins, and ligands on the surface of tumor cells (NCBI Gene 9437). Upon activation, NKp46 signals through its association with ITAM-containing adapter proteins like CD3ζ and FcεRIγ, leading to NK cell degranulation and cytokine secretion (PubMed PMID: 28615651). In clinical development, NKp46 is being utilized as a target for multi-specific NK cell engagers (NKCEs), such as SAR443579, which redirect NK cell cytotoxicity toward malignant cells (Innate Pharma). These therapeutic agents often employ a trifunctional approach, binding NKp46 and CD16 on NK cells while simultaneously targeting a tumor-associated antigen (Sanofi). Beyond oncology, NKp46 has been implicated in the pathogenesis of autoimmune conditions like type 1 diabetes, where it may contribute to the destruction of pancreatic beta cells (PubMed PMID: 22124371). The receptor's specific expression pattern makes it an ideal candidate for targeted immunotherapy with potentially fewer off-target effects compared to T-cell-based therapies.

Other names

CD335NCR1LY94Natural cytotoxicity receptor p46NK-p46

NK cell engagement and activation via multi-specific antibody formats (NKCEs) or direct agonism to trigger tumor cell lysis.