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.

开始日期2018-03-21

申办/合作机构

Incyte Corp.

NCT03341936 / Active, not recruiting临床2期IIT

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

开始日期2018-03-15

申办/合作机构

Dana-Farber Cancer Institute, Inc.

[+1]

NCT03203876 / Completed临床1期

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

开始日期2017-07-14

申办/合作机构

Bristol Myers Squibb Co.

[+1]

100 项与 KIR2DL3 相关的临床结果

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100 项与 KIR2DL3 相关的转化医学

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0 项与 KIR2DL3 相关的专利（医药）

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项与 KIR2DL3 相关的文献（医药）

2024-08-27·Clinical Chemistry and Laboratory Medicine (CCLM)

The role of Killer immunoglobulin-like receptors (KIRs) in the genetic susceptibility to non-celiac wheat sensitivity (NCWS)

Article

作者: Agnello, Luisa ; Vidali, Matteo ; Giuliano, Alessandra ; Tamburello, Martina ; Candore, Giuseppina ; Carroccio, Antonio ; Lo Sasso, Bruna ; Ciaccio, Marcello ; Masucci, Anna ; Vassallo, Roberta ; Gambino, Caterina Maria ; Scazzone, Concetta ; Ciaccio, Anna Maria ; Mansueto, Pasquale ; Massa, Davide ; Seidita, Aurelio

AbstractObjectivesNon-celiac wheat sensitivity (NCWS) is an emerging clinical condition characterized by gastrointestinal and extraintestinal symptoms following the ingestion of gluten-containing foods in patients without celiac disease (CD) or wheat allergy. Despite the great interest for NCWS, the genetic risk factors still need to be fully clarified. In this study, we first assessed the possible contribution of KIR genes and KIR haplotypes on the genetic predisposition to NCWS.MethodsFifty patients with NCWS, 50 patients with CD, and 50 healthy controls (HC) were included in this study. KIR genes and KIR genotyping were investigated in all subjects by polymerase chain reaction with the sequence oligonucleotide probe (PCR-SSOP) method using Luminex technology.ResultsWe found a statistically different distribution of some KIR genes among NCWS, CD, and HC. Specifically, NCWS showed a decreased frequency of KIR2DL1, −2DL3, −2DL5, −2DS2, −2DS3, −2DS4, −2DS5, and −3DS1 genes, and an increased frequency of -3DL1 gene respect to both CD and HC. No difference was detected in the KIR haplotype expression. At the multivariate analysis, KIR2DL5, −2DS4, and −2DS5 were independent predictors of NCWS.ConclusionsOur findings suggest a role of KIR genes in NCWS susceptibility, with KIR2DL5, −2DS4, and −2DS5 having a protective effect. Further large-scale multicentric studies are required to validate these preliminary findings.

2024-08-01·HLA

Killer‐cell immunoglobulin‐like receptor polymorphism is associated with COVID‐19 outcome: Results of a pilot observational study

Article

作者: Bartol‐Sánchez, M. R. ; Alcoceba, M. ; Presa, D. ; Gil‐Etayo, F. J. ; López‐Sánchez, E. ; Sánchez, P. L. ; Chillón, M. C. ; González, M. ; Muñoz, J. L. ; García‐Sanz, R. ; Gutiérrez‐Zufiaurre, M. N. ; Niño‐Ramírez, J. E. ; Boix, F. ; González‐Calle, D. ; García‐Álvarez, M. ; López‐Bernús, A. ; Compán‐Fernández, O. ; Terradillos‐Sánchez, P. ; Eiros, R. ; Marcos, M.

The pathogenesis of COVID‐19 warrants unravelling. Genetic polymorphism analysis may help answer the variability in disease outcome. To determine the role of KIR and HLA polymorphisms in susceptibility, progression, and severity of SARS‐CoV‐2 infection, 458 patients and 667 controls enrolled in this retrospective observational study from April to December 2020. Mild/moderate and severe/death study groups were established. HLA‐A, ‐B, ‐C, and KIR genotyping were performed using the Lifecodes® HLA‐SSO and KIR‐SSO kits on the Luminex® 200™ xMAP fluoroanalyser. A probability score using multivariate binary logistic regression analysis was calculated to estimate the likelihood of severe COVID‐19. ROC analysis was used to calculate the best cut‐off point for predicting a worse clinical outcome with high sensitivity and specificity. A p ≤ 0.05 was considered statistically significant. KIR AA genotype protected positively against severity/death from COVID‐19. Furthermore, KIR3DL1, KIR2DL3 and KIR2DS4 genes protected patients from severe forms of COVID‐19. KIR Bx genotype, as well as KIR2DL2, KIR2DS2, KIR2DS3 and KIR3DS1 were identified as biomarkers of severe COVID‐19. Our logistic regression model, which included clinical and KIR/HLA variables, categorised our cohort of patients as high/low risk for severe COVID‐19 disease with high sensitivity and specificity (Se = 94.29%, 95% CI [80.84–99.30]; Sp = 84.55%, 95% CI [79.26–88.94]; OR = 47.58, 95%CI [11.73–193.12], p < 0.0001). These results illustrate an association between KIR/HLA ligand polymorphism and different COVID‐19 outcomes and remarks the possibility of use them as a surrogate biomarkers to detect severe patients in possible future infectious outbreaks.

2024-07-01·Heliyon

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

Article

作者: 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.

项与 KIR2DL3 相关的新闻（医药）

2022-09-08

·佰傲谷BioValley

单细胞功能蛋白组技术在自身免疫病领域的应用

众所周知，大名鼎鼎的药王“修美乐（阿达木单抗）”，连续10年蝉联“药王”，成为全球销售榜首，从2002年获批上市至今，修美乐全球累计销售额近2000亿美元。这个药有何神奇之处呢？它是全球第一个上市的全人源化TNF-α单克隆抗体药，可用于治疗17种自身免疫相关的疾病，包括类风湿关节炎、强直性脊柱炎、银屑病等。由于专利保护期逐渐到期，预计2023年将有8种来自不同厂家的修美乐类似药上市销售，如安进、辉瑞、诺华等，由此可见自身免疫病领域的广大需求。靶向细胞因子的自身免疫性疾病药物开发随着对自身免疫病和炎症性疾病发病机制的深入研究，有越来越多的新靶点被发现，如内体/溶酶体相关蛋白、microRNA，而细胞因子毫无疑问占据非常重要的地位，经典的自身免疫病和炎症相关靶点通路以TNF、IL-17/IL-23、IL-4/IL-13等为代表。此外还有如IL-1β、IL-5、IL-36、IL-39等均可能成为某些自身免疫病的干预靶点。如治疗哮喘的生物制剂中，Mepolizumab（美泊利单抗）和Reslizumab（瑞替珠单抗）是抗IL -5抗体。Benralizumab（贝那利珠单抗）结合IL-5受体α的α链。Dupilumab（度普利尤单抗）结合到IL-4R的α亚基。治疗哮喘的抗体药作用机制图片来自Allergy. 2020 Jul;75(7):1582-1605.更好地了解自身免疫病的发病机理，以及在这些疾病中发挥关键作用的特定细胞因子模式，有助于我们设计靶向治疗策略。借助IsoPlexis单细胞分泌蛋白组技术，可以对分泌细胞因子的各种免疫细胞，在单细胞水平上的分子作用机制进行更深入的探索，挖掘各种自身免疫疾病在发病、疾病进展和缓解过程中的细胞和分子机制变化，为药物开发提供强有力的依据，同时可也帮助发现新的生物标志物，为开发自免病疗法保驾护航。图示IsoPlexis单细胞功能蛋白组技术检测原理什么是IsoPlexis单细胞分泌蛋白组技术？IsoPlexis单细胞分泌蛋白组技术，首次实现在单细胞水平对免疫细胞分泌的多达32种细胞因子进行分析，找到在免疫应答反应中具有超强作战能力的“超级英雄细胞”。通过独特的“细胞多功能指数（PSI）”更全面地分析免疫细胞的综合功能，以加深对免疫相关疾病的作用机制研究，推进免疫相关疗法的开发，用于肿瘤、抗感染、自身免疫病等领域。在多种自身免疫性疾病研究中，常常发现病人体内存在各种类型的多功能免疫细胞（T细胞、单核细胞等），多功能T细胞是指能同时分泌两种及以上细胞因子的细胞，它们往往比单功能细胞（只分泌一种细胞因子）介导更强烈的免疫反应，从而与自身免疫病的发生或进展密切相关。“多功能细胞”在自身免疫性疾病中的作用1. 类风湿性关节炎与多功能T细胞美国康涅狄格州三一学院（Trinity College）分子风湿病学系的Ursula Fearon教授研究团队2022年在Annals of the Rheumatic Diseases 期刊（影响因子：19.103）发表以下文章，探讨类风湿性关节炎 (RA)、高危个体 (IAR) 和健康对照 (HC) 人群中滑膜组织活检中的致病性和保护性多功能T细胞反应，并确定在临床炎症发展之前在RA关节中富集的新的致病性多功能T细胞群的存在。研究方法：对来自风湿性关节炎（RA，n=118）、高危个体（IAR，n=20）和健康人（HC，n=44）的滑膜活检样本进行单细胞多组学分析，包括RNAseq和流式细胞分析。研究结果：1.在RA患者滑膜组织中，Tfh细胞可塑性增加，CD4 T细胞多功能性增强，Treg细胞记忆反应增强。2. 滑膜组织RNAseq分析显示，T细胞激活和分化途径的富集早于RA疾病前发生。3. 在IAR和RA患者的滑膜组织中，由IL-4和GM-CSF主导的潜在保护性多功能性CD4 T细胞反应向致病性多功能性T细胞反应转变明显。4. 聚类分析显示，高度多功能性CD4+ CD8dim T细胞在IAR和RA中累积，而在健康人滑膜组织中没有。CD4+ CD8dim T细胞显示氧化磷酸化利用增加，这是代谢启动的记忆T细胞的特征。滑膜CD4+ CD8dim T细胞频率与RA疾病活性相关。研究结论：从潜在保护性T细胞转变为致病性T细胞多功能性早于RA临床炎症的发作，为RA的治疗干预提供了机会。2. 克罗恩病克罗恩病是炎症性肠病的一种，属于原因不明的肠道炎症性疾病，是多种因素引起易感人群的自身免疫反应。由于克罗恩病的病因尚未明确，所以疾病仍然难以攻克。研究疾病的发病机制，能够让医疗人员有针对的制定相关的治疗方案，对于病人的治疗非常关键。来自加州大学洛杉矶分校大卫·格芬医学院的Jonathan Braun教授研究团队探讨了NK细胞多功能性在克罗恩病中的作用，研究成果“Human Natural Killer Cells Licensed by KIR Genes Have an Altered Cytokine Program That Modifies CD4+ T Cell Function”发表在Journal of Immunology期刊上。研究方法：作者采用微流控单细胞条形码芯片（SCBC）在单细胞水平评估单个NK细胞的细胞因子分泌谱，分析了数千个NK单细胞和分泌的多种蛋白，以研究NK细胞的多功能性，及在不同疾病条件下介导的保护性和炎性免疫反应异质性。研究结果：1. NK细胞“许可”（licensing）由宿主基因组中KIR2DL3和纯合子HLA-C1的存在决定，导致NK细胞的细胞因子重编程，并促进CD4+ T细胞活化和体外Th17分化。2. 单细胞微流控蛋白组分析表明，“经许可”的NK细胞比“未许可”的NK细胞具有更高的多功能性，表现为更倾向于产生促炎细胞因子，包括IFN-γ、TNF-α、CCL-5和巨噬细胞炎症蛋白(MIP)-1β的产生。3. “经许可”NK细胞产生的细胞因子增加了CD4+ T细胞的增殖和IL-17A/IL-22的产生。抗体阻断实验表明IFN-γ、TNF-α和IL-6在增强T细胞增殖反应中起主要作用。研究结论：由KIR2DL2/3和HLA-C1介导的“NK许可”诱导了一种新的NK细胞因子程序，增强NK细胞多功能性，并可激活诱导促炎CD4+ T细胞，从而为KIR相关的克罗恩肠病等慢性炎症疾病的易感性提供了一种新的生物学机制可能性。3. 多发性硬化多发性硬化（multiple sclerosis，MS）是以中枢神经系统白质炎性脱髓鞘病变为主要特点的自身免疫病，病因和发病机制至今尚未完全明确。既往对MS的研究重点主要集中适应性免疫在MS发病机制和治疗中的作用，而关于天然免疫在MS中的作用的文献相对较少。来自美国康涅狄格大学免疫学和医学系的R. B. Clark研究团队探讨了天然免疫在多发性硬化发病中的作用机制，发表题为“Enhanced TLR2 responses in multiple sclerosis”的文章。研究结果：1. 在MS病人体内可能缺乏微生物诱导的天然免疫调节功能，导致对TLR2反应增强，从而在疾病的发病机制中发挥作用。2. MS对TLR2的反应增强主要来自单核细胞，在MS病人外周血单核细胞的多功能性及多功能指数（PSI）显著高于健康对照者，起主要作用的细胞因子是IL-8。PSI可作为判断MS病人的一个潜力检测指标。3. 在治疗后，单核细胞的多功能性显著下调，提示PSI有可能作为预测MS治疗反应的一个指标。研究结论：单细胞分泌蛋白组技术帮助研究人员深入解析单个免疫细胞的功能表型和全面评估免疫功能状态，为进一步揭示MS疾病的细胞作用机制和治疗提供一个有潜力的生物标志物。4. 系统性红斑狼疮系统性红斑狼疮（SLE）是一种多发于青年女性的累及多脏器的自身免疫性和炎性结缔组织病，本病病因至今尚未肯定，其发病可能与遗传、内分泌、感染、免疫异常和一些环境因素有关。近年来研究发现滤泡辅助性T（Tfh）细胞在B细胞分化为浆细胞分泌免疫球蛋白过程中发挥关键作用，在SLE小鼠模型或SLE患者体内都可观察到Tfh细胞的异常扩增。以Tfh细胞为新的治疗靶点可能成为治疗包括SLE在内的自身免疫性疾病的重要方法。研究结果：1. 比较不同T细胞亚群细胞的功能特性：Naïve T细胞，中央记忆性T细胞（Tcm），和滤泡辅助性T细胞（Tfh），有助于发现在系统性红斑狼疮发病中发挥关键作用的细胞亚群和作用机制。2. 在系统性红斑狼疮病人中可见多功能性T细胞增多，其中产生B细胞辅助因子IL-21和效应因子IL-2、IFN-γ和TNF-α分泌水平增高。研究结论：在系统性红斑狼疮病人身上，Tfh细胞的多功能性（IL-21+ IL-2+ IFN-γ+ TNF-α+）显著增强，从而可能通过影响B细胞功能而诱导疾病发生。靶向细胞因子的自身免疫性疾病药物开发不论是流式细胞分析，还是EliSpot技术，在检测分泌细胞因子的多功能细胞时往往一次只能检测3-5种细胞因子，而无法进行更广泛、更深入的研究。利用领先的IsoPlexis单细胞分泌蛋白组技术，结合IsoCode Human Inflammation单细胞芯片，可对分泌不同细胞因子的T细胞亚群（Th1、Th2、Th17、调节性T细胞、细胞毒性T细胞等）在单细胞水平进行更全面的综合性分析，一次分析多达32种细胞因子，便于：★ 全方位评估疾病不同阶段病人体内的免疫状态，并为早期干预提供可能★ 发现以往因为技术局限而无法触及的新发现，推进医学发展★ 为自身免疫性疾病的药物开发提供坚实的基础，发现新靶点和生物标志物图示IsoCode Human Inflammation芯片可检测的细胞因子种类近期热门视频更多精彩视频，尽在佰傲谷视频号，欢迎关注~本周好文推荐如需转载请联系佰傲谷并在醒目位置注明出处﹀点亮在看，传递信息♥

细胞疗法抗体免疫疗法专利到期