Natural killer cell p46 ligands (NKp46L) (NKp46L)

NKp46 ligands are a heterogeneous group of molecules expressed on the surface of abnormal cells, such as tumor cells or virally infected cells, that serve as critical recognition signals for the innate immune system. These ligands bind to the NKp46 receptor (also known as NCR1 or CD335), a major activating receptor constitutively expressed on Natural Killer (NK) cells, triggering a signaling cascade that leads to the targeted destruction of the abnormal cell [UniProt, 2024]. While the identity of many endogenous tumor ligands remains elusive, known examples include viral hemagglutinins, surface-exposed calreticulin, externalized vimentin, and heparan sulfate proteoglycans [Frontiers in Immunology, 2020]. Additionally, soluble factors like platelet-derived growth factor-DD (PDGF-DD) have been identified as functional ligands that can stimulate NKp46-mediated cytokine production and tumor cell killing [Nature Immunology, 2019]. In the pharmaceutical industry, the NKp46-ligand axis is a focal point for the development of multi-specific NK cell engagers (NKCEs), such as SAR443579 and IPH6101, which are designed to bridge NKp46 on NK cells directly to tumor-specific antigens [Innate Pharma, 2023]. These therapeutic agents aim to bypass the requirement for natural ligand expression on the tumor surface, thereby overcoming immune evasion and enhancing the anti-tumor efficacy of NK cells.

Other names

NCR1 ligandsCD335 ligandsNKp46-LTumor-associated NKp46 ligands

Multi-specific engagement of the NKp46 receptor on Natural Killer cells to induce targeted lysis of cells expressing specific antigens or ligands [Innate Pharma, 2023].