NKG2A (KLRC1)
NKG2A is the brake on NK cells and some killer T cells that is pressed by HLA-E, a molecule tumours raise to look like self. Monalizumab blocks it and is in phase 3 with durvalumab in lung cancer and with cetuximab in head and neck cancer.
Overview
KLRC1 (chromosome 12p13.2) encodes NKG2A, which pairs with CD94 (KLRD1) on cytotoxic and regulatory lymphocytes and recognises the non-classical class Ib molecule HLA-E loaded with signal-sequence peptides from classical class Ia molecules, letting cytotoxic cells monitor MHC class I on healthy cells and tolerate them (UniProt P26715). It is predominantly expressed on NK cells and on subsets of intraepithelial, gamma-delta and memory CD8 T cells (protein level). Monalizumab, an anti-NKG2A antibody, is in the PACIFIC-9 phase 3 study with durvalumab after chemoradiotherapy in stage III non-small-cell lung cancer (NCT05221840) and the INTERLINK-1 phase 3 with cetuximab in head and neck squamous cell carcinoma (NCT04590963).
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · NKG2A is the brake on NK cells and some killer T cells that is pressed by HLA-E, a molecule tumours raise to look like self. Monalizumab blocks it and is in phase 3 with durvalumab in lung cancer and with cetuximab in head and neck cancer.
- 1 · What it is
NKG2A is the brake on NK cells and some killer T cells that is pressed by HLA-E, a molecule tumours raise to look like self. Monalizumab blocks it and is in phase 3 with durvalumab in lung cancer and with cetuximab in head and neck cancer.
- 2 · What goes wrong in cancer
A C-type lectin-like inhibitory receptor; the CD94/NKG2A heterodimer reads HLA-E and signals through ITIMs.
- 3 · How drugs use it
No product in this corpus aims at NKG2A (KLRC1) yet. Checkpoint drugs are antibodies that cover one side of an immune ‘stand down’ handshake so T cells stay active.
External identifiers
Sources: HGNC HGNC:6374 (approved symbol, name, aliases and cross-references); UniProt P26715 (protein name, function and tissue specificity)
Biology
A C-type lectin-like inhibitory receptor; the CD94/NKG2A heterodimer reads HLA-E and signals through ITIMs.
- NK cells; intraepithelial and memory CD8 T-cell subsets (UniProt P26715)
- Non-small-cell lung cancer and head and neck cancer trials of monalizumab
Notes
top- Prevalence not recorded: HGNC and UniProt carry no positivity rates.
Latest papers
topQuery for this target: (TITLE:"NKG2A" OR ABSTRACT:"NKG2A" OR TITLE:"KLRC1" OR ABSTRACT:"KLRC1" OR TITLE:"NKG2-A" OR ABSTRACT:"NKG2-A" OR TITLE:"CD159a" OR ABSTRACT:"CD159a" OR TITLE:"killer cell lectin like receptor C1" OR ABSTRACT:"killer cell lectin like receptor C1") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about NKG2A (KLRC1), not a curated reading list.
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