更新于：2024-11-01

KIR3DL1 x LILRB2 x LILRB1

更新于：2024-11-01

基本信息

关联

项与 KIR3DL1 x LILRB2 x LILRB1 相关的药物

ios H2

靶点

KIR3DL1 x LILRB1 x LILRB2

作用机制

KIR3DL1抑制剂 [+2]

在研机构

ImmunOs Therapeutics AG初创企业

原研机构

ImmunOs Therapeutics AG初创企业

在研适应症

晚期恶性实体瘤 [+1]

非在研适应症-

最高研发阶段临床1期

首次获批国家/地区-

首次获批日期1800-01-20

Bispecific AntiTumor Molecules(ImmunOs)

靶点

KIR3DL1 x LILRB1 x LILRB2 x SIRPα

作用机制

KIR3DL1抑制剂 [+3]

在研机构

ImmunOs Therapeutics AG初创企业

原研机构

ImmunOs Therapeutics AG初创企业

在研适应症

肿瘤

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

项与 KIR3DL1 x LILRB2 x LILRB1 相关的临床试验

NCT05763004 / Recruiting临床1期

A Phase 1a/1b, First-in-human, Open-label, Non-randomized, Multicenter, Dose Escalation and Cohort Expansion Study to Evaluate the Safety, Tolerability, Efficacy, Immunogenicity, Pharmacokinetics, and Pharmacodynamics of IOS 1002 Administered Alone and in Combination with Pembrolizumab, a PD-1 Monoclonal Antibody in Advanced Solid Tumors

The goal of this clinical trial is to learn about IOS-1002 in patients with solid tumors.
The main questions it aims to answer are:
* To determine the safety and tolerability of various doses of IOS-1002 administered alone and/or in combination with KEYTRUDA® (pembrolizumab) in a single dose escalation scheme
* To determine the safety, tolerability and efficacy of a selected dose of IOS-1002 administered every 2 weeks alone and in combination with a PD-1 Antibody
The study will be conducted in 3 parts:
* Part A (Phase 1a, monotherapy and combination therapy dose escalation): IOS-1002 alone and IOS-1002 plus PD-1 mAb in patients with advanced solid tumors
* Part B (Phase 1b, monotherapy cohort expansion): IOS-1002 alone in patients with advanced solid tumors
* Part C (Phase 1b, combination therapy cohort expansion): IOS-1002 plus PD-1 mAb in patients with advanced solid tumors.

开始日期2023-03-15

申办/合作机构

ImmunOs Therapeutics AG初创企业

[+1]

100 项与 KIR3DL1 x LILRB2 x LILRB1 相关的临床结果

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100 项与 KIR3DL1 x LILRB2 x LILRB1 相关的转化医学

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0 项与 KIR3DL1 x LILRB2 x LILRB1 相关的专利（医药）

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项与 KIR3DL1 x LILRB2 x LILRB1 相关的文献（医药）

2007-05-01·European Journal of Immunology3区 · 医学

Interaction of HLA‐B27 homodimers with KIR3DL1 and KIR3DL2, unlike HLA‐B27 heterotrimers, is independent of the sequence of bound peptide

3区 · 医学

Article

作者: Li Ye Chen ; Kati di Gleria ; Cynthia Wright ; Antoni Chan ; Paul Bowness ; Simon Kollnberger ; Andrew McMichael ; Mei-Yi Sun

AbstractHLA‐B27 can form beta‐2 microglobulin (β2m)‐associated heterotrimers (HLA‐B27) and β2m‐free homodimers (B272). Here, we study the role of complexed peptide in the interaction of these forms of B27 with the killer cell immunoglobulin (Ig)‐like receptors KIR3DL1 and KIR3DL2 and with Ig‐like transcripts LILRB1 and LILRB2. HLA‐B27 tetramers complexed with three of five different naturally processed self peptides and three of seven pathogen‐derived epitopes bound to KIR3DL1‐expressing transfectants and NK cells. Heterotrimeric complexes containing peptides with charged amino acids at position 8 did not bind to KIR3DL1; however, studies with analogue peptides demonstrated that these are not the only peptide residues involved in binding. KIR3DL1 ligation by HLA‐B27 inhibited NK cell IFN‐γ production in a peptide‐dependent fashion. B27 but not HLA‐A2, B7 or B57 heavy chains formed homodimers in the presence of peptide epitopes. B272 bound to KIR3DL1, KIR3DL2 and LILRB2 but not LILRB1. KIR3DL2 ligation by B272 inhibited NK and T cell IFN‐γ production. By contrast with HLA heterotrimers, B272 binding to KIR did not depend on the sequence of the bound peptide. Differences in KIR binding to classical HLA and B272 could be involved in the pathogenesis of spondyloarthritis.

2002-11-01·Arthritis & Rheumatism

Cell‐surface expression and immune receptor recognition of HLA–B27 homodimers

Article

作者: Simon Kollnberger ; Andrew McMichael ; Christelle Retiere ; Paul Bowness ; Lucy Bird ; Mei-Yi Sun ; Veronique M. Braud

AbstractObjectiveHLA–B27 is capable of forming in vitro a heavy‐chain homodimer structure lacking β2‐microglobulin. We undertook this study to ascertain if patients with spondylarthritis express β2‐microglobulin–free HLA–B27 heavy chains in the form of homodimers and receptors for HLA–B27 homodimers.MethodsExpression of HLA–B27 heavy chains by mononuclear cells was analyzed by fluorescence‐activated cell sorter staining, Western blotting with the monoclonal antibody HC‐10, and 2‐dimensional isoelectric focusing. Fluorescence‐labeled tetrameric complexes of HLA–B27 heavy‐chain homodimers were constructed in which each dimer comprised one His‐tagged heavy chain and one biotinylated heavy chain, and were used to stain patient and control mononuclear cells and transfected cell lines.ResultsPatients with spondylarthritis expressed cell‐surface HLA–B27 homodimers. Populations of synovial and peripheral blood monocytes, and B and T lymphocytes from patients with spondylarthritis, and controls carried receptors for HLA–B27 homodimers. Experiments with transfected cell lines demonstrated that KIR3DL1 and KIR3DL2, and immunoglobulin‐like transcript 4 (ILT4), but not ILT2, are receptors for HLA–B27 homodimers.ConclusionPatients with spondylarthritis express both HLA–B27 heavy‐chain homodimers and receptors for HLA–B27 homodimers. This may be of significance with regard to disease pathogenesis.

2001-11-15·The Journal of Immunology2区 · 医学

Cutting Edge: Leukocyte Receptor Complex-Encoded Immunomodulatory Receptors Show Differing Specificity for Alternative HLA-B27 Structures

2区 · 医学

Article

作者: Trowsdale, John ; Wilson, Michael J. ; Haude, Anja ; Allen, Rachel L. ; Raine, Tim

AbstractWe studied recognition of the disease-associated HLA-B27 allele by immunomodulatory receptors encoded within the leukocyte receptor complex. HLA class I are ligands for members of the killer Ig receptor (KIR) and Ig-like transcript (ILT)/LIR/LILR families (the new LILR nomenclature is described at www. gene.ucl.ac.uk/nomenclature/genefamily/lilr.html). Members of these families bound HLA-B27 in both classical and β2 microglobulin-independent forms. Classical complexes bound ILT2, ILT4, and LIR6 transfectants but not ILT1, ILT3, or ILT5. A free H chain form of HLA-B27 bound ILT4 and LIR6. Both forms of HLA-B27 bound KIR3DL1 transfectants. HLA-B27 free H chain bound CD14+ cells in PBL from healthy controls, consistent with ILT4 expression on monocytes. Alternative recognition of different forms of HLA-B27 by KIR or ILT could influence their immunomodulatory function and may imply a role in inflammatory disease.