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更新于：2025-05-07

TRAIL受体 x TWEAKR

更新于：2025-05-07

基本信息

关联

项与 TRAIL受体 x TWEAKR 相关的药物

TSCP-2

靶点

TRAIL受体 x TWEAKR

作用机制

TRAIL受体调节剂 [+1]

在研机构

KAHR Medical Ltd.

原研机构

KAHR Medical Ltd.

在研适应症

类风湿关节炎

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

100 项与 TRAIL受体 x TWEAKR 相关的临床结果

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100 项与 TRAIL受体 x TWEAKR 相关的转化医学

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0 项与 TRAIL受体 x TWEAKR 相关的专利（医药）

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项与 TRAIL受体 x TWEAKR 相关的文献（医药）

2017-08-01·Cancer Letters1区 · 医学

Fn14·TRAIL fusion protein is oligomerized by TWEAK into a superefficient TRAIL analog

1区 · 医学

Article

作者: Makdasi, Efi ; Szafer, Fanny ; Dranitzki Elhalel, Michal ; Tzdaka, Kobi ; Shani, Noam ; Prigozhina, Tatyana B ; Aronin, Alexandra ; Amsili, Shira

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) demonstrates specific anti-cancer activity, but insufficient efficacy in patients. A fusion protein Fn14·TRAIL, that combines soluble TRAIL molecule with a specific TWEAK receptor Fn14, is a better apoptosis-inducer for hepatocellular carcinomas than soluble TRAIL. However, Fn14·TRAIL does not effectively induce apoptosis in tumors of the lymphoid origin. As malignant cell apoptosis is strongly enhanced by secondary oligomerization of TRAIL, we tested the hypothesis that soluble Fn14·TRAIL can be oligomerized and become more active by adding TWEAK, a cytokine secreted in the tumor environment. We revealed that TWEAK and Fn14·TRAIL spontaneously formed a stable complex that induced apoptosis of malignant lymphoblasts earlier and more efficiently than TRAIL. The TWEAK-modified Fn14·TRAIL oligomer bound to target cells and delivered apoptotic signaling via TRAIL receptors. The oligomer induced faster and stronger cleavage of procaspase-8, -9, and -3; BID; poly-ADP ribose polymerase; and RIP compared to TRAIL. The oligomer also reduced expression of the anti-apoptotic proteins c-FLIP short and cIAP-1. Our data indicate that Fn14·TRAIL can be converted into a highly effective TRAIL oligomer upon binding to TWEAK.

2015-01-01·International journal of clinical and experimental medicine

Comparison of cytokine expressions in acute myocardial infarction and stable angina stages of coronary artery disease.

Article

作者: Wang, Lemin ; Yan, Wenwen ; Wen, Siwan ; Duan, Qianglin ; Ding, Lin

OBJECTIVETo investigate the differential gene expression of cytokines and compare their impacts on the immune functions among the acute myocardial infarction patients (AMI), the stable angina patients (SA) and the controls.METHODS20 patients with AMI, 20 patients with SA and 20 healthy volunteers were recruited into the study. Whole human genome microarray analysis was used to detect the gene expression differences in interferons, interleukins, chemokines, tumor necrosis factors and associated receptors in peripheral blood mononuclear cells (PBMCs) among three groups.RESULTSCompared with SA patients and the controls respectively, in AMI patients, IFNα2, IFNαR1, IFNαR2, IFNγR1, IFNγR2, L1β, IL16, IL18, Cxcl1, Cxcl2, Cxcl6, CxcR2, CxcR4, LIGHT, TNFR1, LT-βR, CD137, TRAILR, and TWEAKR mRNA expressions were significantly up-regulated (P<0.05), while Ccl5, Ccl24, Ccl28, CcR5, TWEAK, CD40, CD27, and BAFFR mRNA expressions were significantly down-regulated (P<0.05). But, there was no significant difference in cytokine expression between the SA patients and the controls.CONCLUSIONIn AMI patients, mRNA expression levels of cytokines were imbalanced, indicating the dysfunction of the immune system. Together with no significant change of cytokines was observed between the SA and controls, showing the different cytokine related immune activity in the AMI and SA patients.

2013-12-01·Journal of Neuroinflammation1区 · 医学

Amelioration of autoimmune neuroinflammation by the fusion molecule Fn14·TRAIL

1区 · 医学

ArticleOA

作者: Michal Irony-Tur-Sinai ; Hodaya Prinz-Hadad ; Tatyana B Prigozhina ; Talma Brenner ; Tehila Mizrachi ; Michal Dranitzki-Elhalel ; Alexandra Aronin

AbstractBackgroundMultiple sclerosis (MS) is a, T cell-mediated autoimmune disease, the management of which remains challenging. The recently described fusion protein, Fn14·TRAIL, combining the extracellular domain of Fn14 (capable of blocking the pro-inflammatory TWEAK ligand) fused to the extracellular domain of the TRAIL ligand (capable of sending apoptotic signals through its receptors on activated inflammatory cells) was designed to modulate the immune system as an anti-inflammatory agent. The present study explores the efficacy of this purified protein as an anti-inflammatory agent, using the animal model of MS - experimental autoimmune encephalomyelitis (EAE).MethodsEAE was induced by myelin oligodendrocyte glycoprotein (MOG). Fn14·TRAIL or vehicle were injected daily for 4 to 16 days, at different time points after disease induction. Animals were examined daily and evaluated for EAE clinical signs. Lymphocytes were analyzed for ex vivo re-stimulation, cytokine secretion, transcription factor expression and subtype cell analysis. Spinal cords were checked for inflammatory foci. The Mann- Whitney rank sum test, Student’s t-test or ANOVA were used for statistical analysis.ResultsSignificant improvement of EAE in the group treated with Fn14·TRAIL was noted from day 6 of disease onset and lasted until the end of follow-up (day 40 from disease induction), even in animals treated for 4 days only. Clinical improvement was linked to decreased lymphocyte infiltrates in the central nervous system (CNS) and to decreased Th1 and Th17 responses and to increased number of T- regulatory in the treated mice. No liver or kidney toxicity was evident. In vitro assays established the ability of Fn14·TRAIL to induce apoptosis of T cell lines expressing TRAIL receptors and TWEAK.ConclusionsIn this study we established the potency of Fn14·TRAIL, a unique fusion protein combining two potentially functional domains, in inhibiting the clinical course of EAE, even when given for a short time, without apparent toxicity. These findings make Fn14·TRAIL a highly promising agent to be used for targeted amelioration of neuro-inflammatory processes, as well as other autoimmune pathologies.

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