Killer cell lectin-like receptor C1 (NKG2A) (NKG2A)

Killer cell lectin-like receptor C1, commonly known as NKG2A (UniProt: P26715), is an inhibitory receptor primarily expressed on natural killer (NK) cells and a subset of cytotoxic CD8+ T cells (PubMed: 30531946). It functions as a critical immune checkpoint by forming a heterodimer with CD94 to recognize HLA-E, a non-classical MHC class I molecule typically expressed on healthy cells to signal 'self' and prevent immune attack (PubMed: 9486650). In many cancers, tumor cells overexpress HLA-E to exploit this pathway, effectively evading immune surveillance by suppressing the activity of infiltrating NK and T cells (PubMed: 30531946). Therapeutic strategies, such as the monoclonal antibody monalizumab (IPH2201), aim to block the NKG2A/HLA-E interaction to restore the immune system's ability to identify and destroy malignant cells (AstraZeneca, Innate Pharma). As a 'next-generation' checkpoint inhibitor, NKG2A is often studied in combination with other immunotherapies, such as PD-1/PD-L1 inhibitors, to overcome resistance and enhance clinical outcomes in various solid tumors (PubMed: 30531946).

Other names

KLRC1CD159aNKG2-ACD94/NKG2A receptor complexKiller cell lectin-like receptor subfamily C member 1

Monalizumab is a humanized IgG4 monoclonal antibody that acts as an antagonist by binding to the NKG2A receptor. This blocks the interaction between the NKG2A/CD94 heterodimer and its ligand, HLA-E, which is often overexpressed on tumor cells. By preventing this inhibitory signal, the drug restores and enhances the cytotoxic activity of natural killer (NK) cells and CD8+ T cells against the tumor (PubMed: 30531946).