Natural cytotoxicity triggering receptor 1 and 3 (NKp46 and NKp30) (NKp46/NKp30)

Natural cytotoxicity receptors (NCRs), specifically NKp46 (NCR1) and NKp30 (NCR3), are critical activating receptors belonging to the immunoglobulin superfamily. While primarily identified on Natural Killer (NK) cells, they are also significantly expressed on Cytokine-Induced Killer (CIK) cells, which are ex vivo expanded T cells (mostly CD3+CD56+) used in adoptive immunotherapy. These receptors recognize a diverse array of ligands, including the tumor-associated protein B7-H6 for NKp30 and viral hemagglutinins for NKp46, triggering non-MHC-restricted cytotoxicity against malignant or infected cells. In the context of CIK cell therapy, the expression density of NKp30 and NKp46 is a key determinant of anti-tumor efficacy and is often used to characterize the potency of the cell product. Therapeutic development focuses on utilizing these receptors as anchors for multispecific engagers (e.g., ANKETs) or enhancing their signaling to overcome immune evasion in the tumor microenvironment. Consequently, they represent vital targets for improving the precision and strength of adoptive cell therapies in both liquid and solid cancers.

Other names

NCR1NCR3CD335CD337Natural cytotoxicity receptorsNCRsp46p30

Activation of cytotoxic signaling pathways via association with ITAM-containing adapter proteins (e.g., CD3-zeta or Fc-epsilon-RI-gamma), leading to degranulation, perforin/granzyme release, and secretion of pro-inflammatory cytokines like IFN-gamma.