Natural cytotoxicity triggering receptor 1 (NCR1) (NCR1)

Natural cytotoxicity triggering receptor 1 (NCR1), widely known as NKp46 or CD335, is a type I transmembrane glycoprotein and a defining activating receptor for Natural Killer (NK) cells [1]. It belongs to the immunoglobulin superfamily and is essential for the innate immune system's ability to recognize and destroy tumor cells and virus-infected cells [2]. NCR1 functions by binding to a variety of ligands, including viral hemagglutinins and various tumor-associated molecules, subsequently signaling through ITAM-containing adapter proteins like CD3ζ and FcεRIγ to initiate NK cell cytotoxicity and cytokine secretion [1, 2]. In the context of oncology, NCR1 is a primary target for the development of multi-specific NK cell engagers (NKCEs), which are designed to co-engage NKp46 and CD16 on NK cells while simultaneously binding to tumor-specific antigens [3]. These therapies aim to harness the potent anti-tumor activity of NK cells with potentially fewer side effects than T-cell-directed therapies [4]. Additionally, NCR1 has been implicated in the destruction of pancreatic beta cells in type 1 diabetes, suggesting its role as a therapeutic target in autoimmune conditions [2].

Other names

NKp46CD335Natural cytotoxicity determinant 1LY94Lymphocyte antigen 94Natural killer cell p46-related protein

NK cell engagement and activation via multi-specific antibody binding to trigger targeted tumor cell lysis