KIR2DL1 (inhibitory KIR)
Inhibitory KIRs are the receptors NK cells use to recognise a person's own HLA-C and stand down. Lirilumab, an antibody that blocks three of them, reached phase 2 but was dropped for blood cancers.
Overview
KIR2DL1 (chromosome 19q13.42) is a receptor on NK cells for HLA-C alleles such as Cw4 and Cw6 that inhibits NK activity and so prevents lysis of the cell it recognises (UniProt P43626); KIR2DL3 does the same for HLA-Cw1, Cw3 and Cw7 (UniProt P43628). Lirilumab, an antibody against KIR2DL1, KIR2DL2 and KIR2DL3, was tested in phase 1/2 with nivolumab in solid tumours (NCT01714739); enrolment in myelodysplastic syndromes stopped after the sponsor decided not to pursue lirilumab for myeloid malignancies (NCT02599649), and a relapsed AML study ended because response rates did not reach the anticipated minimum of 30 percent (NCT02399917).
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · Inhibitory KIRs are the receptors NK cells use to recognise a person's own HLA-C and stand down. Lirilumab, an antibody that blocks three of them, reached phase 2 but was dropped for blood cancers.
- 1 · What it is
Inhibitory KIRs are the receptors NK cells use to recognise a person's own HLA-C and stand down. Lirilumab, an antibody that blocks three of them, reached phase 2 but was dropped for blood cancers.
- 2 · What goes wrong in cancer
Immunoglobulin-like receptors with long cytoplasmic tails (2DL, 3DL) inhibit through ITIMs; short-tailed KIRs activate. This record stands for the inhibitory KIR2DL group the antibody binds.
- 3 · How drugs use it
No product in this corpus aims at KIR2DL1 (inhibitory KIR) 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:6329 (approved symbol, name, aliases and cross-references); UniProt P43626 (protein name, function and tissue specificity)
Biology
Immunoglobulin-like receptors with long cytoplasmic tails (2DL, 3DL) inhibit through ITIMs; short-tailed KIRs activate. This record stands for the inhibitory KIR2DL group the antibody binds.
- NK cells (UniProt P43626)
- Myelodysplastic syndromes and acute myeloid leukaemia trials of lirilumab (terminated)
Notes
top- Prevalence not recorded: HGNC and UniProt carry no positivity rates.
Latest papers
topQuery for this target: (TITLE:"KIR2DL1" OR ABSTRACT:"KIR2DL1" OR TITLE:"inhibitory KIR" OR ABSTRACT:"inhibitory KIR" OR TITLE:"KIR" OR ABSTRACT:"KIR" OR TITLE:"CD158a" OR ABSTRACT:"CD158a" OR TITLE:"p58.1" OR ABSTRACT:"p58.1" OR TITLE:"KIR2DL2" OR ABSTRACT:"KIR2DL2") 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 KIR2DL1 (inhibitory KIR), not a curated reading list.
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