Natural cytotoxicity receptor family (NCR) (NCR)

Natural cytotoxicity receptors (NCRs) are a group of type I transmembrane proteins belonging to the immunoglobulin superfamily, primarily expressed on Natural Killer (NK) cells. The family consists of three members: NKp46 (NCR1), NKp44 (NCR2), and NKp30 (NCR3), which serve as key activating receptors in the innate immune response (UniProt O76036, O95944, O14931). These receptors recognize a diverse array of ligands, including viral proteins, bacterial components, and stress-induced molecules like B7-H6 or BAG6 expressed on tumor and stromal cells (PubMed 19525962, PubMed 23548215). Upon ligand binding, NCRs signal through ITAM-containing adapter molecules to trigger NK cell degranulation and the secretion of pro-inflammatory cytokines such as interferon-gamma. In oncology, NCRs are being targeted by novel multi-specific NK cell engagers (NKCEs), such as SAR443579, which are designed to co-engage NKp46 and tumor antigens to promote targeted cell lysis (ClinicalTrials.gov NCT05086315). These therapeutic strategies aim to harness the potent anti-tumor capacity of NK cells while minimizing the systemic toxicity often associated with T-cell-directed therapies.

Other names

NKp46NKp44NKp30NCR1NCR2NCR3CD335CD336CD337

Agonism of activating receptors to trigger NK cell-mediated lysis of target cells; use of multi-specific engagers to recruit NK cells to tumor antigens.