Target General Infomation
Target ID
T35289 (Former ID: TTDI02343)
Target Name
NKG2 D activating NK receptor (KLRK1)
Synonyms
NKG2Dactivating NK receptor; NKG2D type II integral membrane protein; NKG2D; NKG2-D-activating NK receptor; NKG2-D type II integral membrane protein; NK cell receptor D; Killer cell lectinlike receptor subfamily K member 1; Killer cell lectin-like receptor subfamily K member 1; D12S2489E; CD314
Gene Name
KLRK1
Target Type
Clinical trial target
[1]
Disease [+] 5 Target-related Diseases +
1 Crohn disease [ICD-11: DD70]
2 Acute myeloid leukaemia [ICD-11: 2A60]
3 Colorectal cancer [ICD-11: 2B91]
4 Multiple myeloma [ICD-11: 2A83]
5 Myelodysplastic syndrome [ICD-11: 2A37]
Function
Provides both stimulatory and costimulatory innate immune responses on activated killer (NK) cells, leading to cytotoxic activity. Acts as a costimulatory receptor for T-cell receptor (TCR) in CD8(+) T-cell-mediated adaptive immune responses by amplifying T-cell activation. Stimulates perforin-mediated elimination of ligand-expressing tumor cells. Signaling involves calcium influx, culminating in the expression of TNF-alpha. Participates in NK cell-mediated bone marrow graft rejection. May play a regulatory role in differentiation and survival of NK cells. Binds to ligands belonging to various subfamilies of MHC class I-related glycoproteins including MICA, MICB, RAET1E, RAET1G, RAET1L/ULBP6, ULBP1, ULBP2, ULBP3 (ULBP2>ULBP1>ULBP3) and ULBP4. Function as an activating and costimulatory receptor involved in immunosurveillance upon binding to various cellular stress-inducible ligands displayed at the surface of autologous tumor cells and virus-infected cells.
UniProt ID
NKG2D_HUMAN
Sequence
MGWIRGRRSRHSWEMSEFHNYNLDLKKSDFSTRWQKQRCPVVKSKCRENASPFFFCCFIA
VAMGIRFIIMVAIWSAVFLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNW
YESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLT
IIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTV
Drugs and Modes of Action
Clinical Trial Drug(s) [+] 5 Clinical Trial Drugs +
1 NN8555 Drug Info Phase 2 Crohn disease [1]
2 CM-CS1 T-cell Drug Info Phase 1 Multiple myeloma [2]
3 CYAD-101 Drug Info Phase 1 Colorectal cancer [3]
4 NKR-2 CAR-T Cells Drug Info Phase 1 Myelodysplastic syndrome [4]
5 NKR-2 cells Drug Info Phase 1 Acute myeloid leukaemia [5], [6]
Mode of Action [+] 2 Modes of Action +
Antagonist [+] 1 Antagonist drugs +
1 NN8555 Drug Info [1]
CAR-T-Cell-Therapy [+] 4 CAR-T-Cell-Therapy drugs +
1 CM-CS1 T-cell Drug Info [2]
2 CYAD-101 Drug Info [3]
3 NKR-2 CAR-T Cells Drug Info [4]
4 NKR-2 cells Drug Info [5], [6]
References
REF 1 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
REF 2 ClinicalTrials.gov (NCT02203825) Safety Study of Chimeric Antigen Receptor Modified T-cells Targeting NKG2D-Ligands
REF 3 ClinicalTrials.gov (NCT03692429) alloSHRINK - Standard cHemotherapy Regimen and Immunotherapy With Allogeneic NKG2D-based CYAD-101 Chimeric Antigen Receptor T-cells
REF 4 ClinicalTrials.gov (NCT03612739) EPITHINK: Epigenetic Drug Treatment and Therapeutic Immunotherapy With NKR-2
REF 5 ClinicalTrials.gov (NCT03310008) Dose Escalation and Dose Expansion Phase I Study to Assess the Safety and Clinical Activity of Multiple Doses of NKR-2 Administered Concurrently With FOLFOX in Colorectal Cancer With Potentially Resectable Liver Metastases
REF 6 ClinicalTrials.gov (NCT03370198) Hepatic Transarterial Administrations of NKR-2 in Patients With Unresectable Liver Metastases From Colorectal Cancer

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