Last update 19 Sep 2024

KIR2DS1

Last update 19 Sep 2024

Basic Info

Synonyms

CD158 antigen-like family member H, CD158H, EB6ActI

+ [5]

Introduction

Receptor on natural killer (NK) cells for some HLA-C alleles such as w6. Does not inhibit the activity of NK cells.

Drugs associated with KIR2DS1

Lirilumab

Target

KIR2DL1 x KIR2DL2 x KIR2DL3 x KIR2DS1 x KIR2DS2

Mechanism

KIR2DL1 antagonists [+4]

Active Org.

Bristol Myers Squibb Co. [+1]

Originator Org.

Innate Pharma SA

Active Indication

Recurrent Squamous Cell Carcinoma of the Head and Neck [+1]

Inactive Indication

Acute Myeloid Leukemia [+8]

Drug Highest PhasePhase 2

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Clinical Trials associated with KIR2DS1

NCT03347123 / TerminatedPhase 1/2

A Phase 1/2, Open-Label, Dose-Escalation, Safety, Tolerability, and Efficacy Study of Epacadostat and Nivolumab in Combination With Immune Therapies in Subjects With Advanced or Metastatic Malignancies (ECHO-208)

The purpose of this study is to determine the safety, tolerability, and efficacy of epacadostat when given in combination with nivolumab and ipilimumab, and in combination with nivolumab and lirilumab, in participant with advanced or metastatic malignancies.

Start Date21 Mar 2018

Sponsor / Collaborator

Incyte Corp.

NCT03341936 / Active, not recruitingPhase 2IIT

Neodjuvant Nivolumab and Lirilumab, Followed by Surgery, Followed by Adjuvant Nivolumab and Lirilumab, in Patients With Relapsed, Resectable Squamous Cell Carcinoma of the Head and Neck

This research study is studying a combination of two immunotherapy drugs, as a possible treatment for locoregionally recurrent squamous cell carcinoma of the head and neck.
The immunotherapy drugs involved in this study are:
Nivolumab (Opdivo™)
Lirilumab

Start Date15 Mar 2018

Sponsor / Collaborator

Dana-Farber Cancer Institute, Inc.

[+1]

NCT03203876 / CompletedPhase 1

A Phase 1 Study of the Safety and Pharmacokinetics of Anti-KIR Monoclonal Antibody (Lirilumab, BMS-986015) in Combination With Anti-PD-1 Monoclonal Antibody (Nivolumab,BMS-936558) or in Combination With Nivolumab and Anti-CTLA-4 Monoclonal Antibody (Ipilimumab, BMS-734016) in Advanced and/or Metastatic Solid Tumors

The purpose of this study is to determine whether lirilumab in combination with nivolumab or in combination with nivolumab and ipilimumab is safe in the treatment of advanced and/or metastatic solid tumors

Start Date14 Jul 2017

Sponsor / Collaborator

Bristol Myers Squibb Co.

[+1]

100 Clinical Results associated with KIR2DS1

100 Translational Medicine associated with KIR2DS1

0 Patents (Medical) associated with KIR2DS1

203

Literatures (Medical) associated with KIR2DS1

01 Jul 2024·Current Molecular Medicine

Impact of HLA Class I Antigen, Killer Inhibitory Receptor, and FCGR3A Genotypes on Breast Cancer Susceptibility and Tumor Stage

Article

Author: Novelli, Giorgio ; Del Beato, Tiziana ; Sconocchia, Giuseppe ; Buonomo, Oreste ; Canossi, Angelica ; Papola, Franco ; Venditti, Adriano ; Rossi, Piero ; Aureli, Anna

Background:The identification in breast cancer (BC) of novel genetic biomarkers regulating natural killer (NK) cell function, including the HLA, KIR, and CD16A (FCGR3A), may be still a challenge.Objective:We aimed to evaluate whether the combined effect of these polymorphisms has an impact on BC susceptibility and progression.Methods:47 BC Italian patients and healthy individuals (39 females and 66 males/ females) were genotyped by Sanger sequencing (HLA-C exon 2-4 and FCGR3A- 158V/F, 48L/R/H) and PCR-SSP typing (KIR genes).Results:HLA-C gene allele analysis showed the group C1, with HLA-C*07:02:01 allele, to be significantly associated with tumor progression (16.7% vs. 4.0%, p=0.04, OR=4.867), and instead, group C2, with HLA-C*05:01:01, was protective against disease susceptibility (0.0% vs. 7.2%, p=0.019, OR=0.087). In addition, we highlighted a significant reduction of the KIR2DS4ins in BC patients (pcorr.=0.022) and an increased combined presence of KIR2DL1 and KIR2DS1 genes in advanced BC patients compared to earlier stages (66.7% vs. 19.2%, p=0.002). The concurrent lack of KIR2DL2 and KIR2DS4 genes in the presence of HLA-C2 alleles was significantly associated with increased susceptibility to BC (p=0.012, OR=5.020) or with lymph node involvement (p=0.008, OR=6.375). Lastly, we identified different combinations of the FCGR3A-48/158 variants and KIR genes in BC patients compared to controls.Conclusion:Our findings suggest that in the development of BC probably exists a disorder of the NK innate immunity influenced by KIR/HLA-C gene content and FCGR3A-158 polymorphisms and that the combined analysis of these biomarkers might help predict genetic risk scores for tailored screening of BC patients in therapy.

01 Jul 2024·Heliyon

Association between Killer Immunoglobulin-like receptor genes and susceptibility to inflammatory bowel disease: An updated meta-analysis

Article

Author: García-Torreros, César ; Graciano-Machuca, Omar ; Recendiz-Nuñez, Miguel Ángel ; Huerta-Olvera, Selene Guadalupe ; Enciso-Vargas, Moisés ; Sifuentes-Franco, Sonia ; Ponce, Giovanna Isabel ; Rodríguez-Sánchez, Irám Pablo

BackgroundSeveral studies have associated members of the KIR genes as susceptibility factors to inflammatory bowel diseases (IBD): ulcerative colitis (UC) and Crohn's disease (CD).ObjectivesTo assess the association between the presence and absence KIR genes and IBD susceptibility through a meta-analysis.MethodA systematic search was performed through the PubMed, Scopus, and Web of Science databases to obtain relevant articles published before March 2024. Associations between genes and susceptibility to IBDs were estimated by OR with 95 % CI.ResultsWe found positive associations of the KIR2DS1 and KIR2DS3 genes with susceptibility to UC, while the KIR2DL3 and KIR2DS4 ^full genes showed a negative association. In addition, the KIR2DS1, KIR2DS3, KIR2DS4, KIR2DS5, and KIR3DS1 genes showed a positive association with susceptibility to CD, whereas the KIR2DL1 gene showed a negative association.ConclusionsOur meta-analysis indicates that individuals carrying the KIR2DS1 and KIR2DS3 genes exhibit increased susceptibility to UC, whereas carriers of the KIR2DS1, KIR2DS3, KIR2DS4, KIR2DS5, and KIR3DS1 genes are more prone to CD. However, further studies are required to clarify the role of the KIR genes and their corresponding ligands in the pathology of IBD.

01 Apr 2024·Placenta

HLA-G isoforms, HLA-C allotype and their expressions differ between early abortus and placenta in relation to spontaneous abortions

Article

Author: Singha, Sushmita ; Hazarika, Sumita Gogoi ; Baruah, Shashi ; Bora, Mayuri ; Madan, Taruna ; Deka, Gitanjali

INTRODUCTIONSpontaneous abortion (SAB) affects approximately 10% of clinically recognized pregnancies. Fetal trophobalst invasion and remodeling of maternal spiral arteries is reported to be dependent on crosstalk between HLA-C/HLA-G expressed on extra villous trophoblast (EVTs)and Killer cell Immunoglobin like receptors (KIRs) of decidual NK (dNK). Immune dysfunction in decidua contributes to early miscarriage.METHODOLOGYThe study used mother neonate paired cord blood and term placenta samples (n = 46), elective abortus (n = 17,gestational age = 10-12 weeks of pregnancy) and SAB abortus (n = 24, gestational age = 12-15 weeks of pregnancy) for HLA-G, KIR2D and HLA-C. In addition, term placenta was collected from women with history of spontaneous pregnancy loss (n = 24) and women with history of live birth (n = 32). SSP-PCR was used for genotyping, RT-PCR for gene expression, copy number variation (CNVs) and HLA-C allotyping and ELISA for protein expression studies.RESULTSMembrane bound HLA-G4 isoform proportion was higher 39.28%, p = 0.02) in term placenta. SAB abortus had higher proportion of HLA-G3 (50%),while elective abortus exhibited higher proportion of soluble isoforms (HLA-G5, = 5.9, HLA-G6 = 5.9%, HLA-G7 = 11.8%). Higher inhibitory KIR2DL1 content and copy numbers with lower HLA-C2 in SAB contrasted with higher copy numbers of KIR2DS1(p = 0.001), KIR2DS1⁺/2DL1⁺- HLA-C2 combined genotype in healthy placenta. Elevated KIR2D protein levels (p = 0.001), and concurrently, HLA-C levels were upregulated in healthy placenta.CONCLUSIONOur data supports lower cognate receptor ligand KIR2DS1+/2DL1+ HLA-C2 together with predominance of HLA-G3 isoform in SAB as confounding factors in spontaneous pregnancy loss. HLA-G isoforms and expression differed between first trimester abortus and term placenta suggesting temporal modulation and marks novelty of the study.

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KIR2DS1

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