Therapeutic Targets of the TNF Superfamily

Therapeutic Targets of the TNF Superfamily pdf epub mobi txt 电子书 下载 2026

出版者:
作者:Grewal, Iqbal S. 编
出品人:
页数:237
译者:
出版时间:2009-2
价格:$ 247.47
装帧:
isbn号码:9780387895192
丛书系列:
图书标签:
  • TNF superfamily
  • Therapeutic targets
  • Immunology
  • Drug discovery
  • Inflammation
  • Cancer
  • Autoimmune diseases
  • Receptor signaling
  • Biomarkers
  • Target validation
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具体描述

TNF superfamily has been the most highly investigated area of basic medical research for over two decades. These investigations have benefited from the enormous growth in our understanding of the principal functions of the immune system and the explosion in the knowledge involved in regulation of normal and pathological immune response. In addition, much has been learned about the molecular mechanisms of programmed cell death and the escape of tumor cells from apoptotic demise and from discovery of the key role played by TNF ligands in this process. As the functioning of these superfamily members is very complex, understanding TNF ligands and their receptor biology requires a melange of research activities in many different disciplines including organ development, molecular biology, experimental pathology, and immunology. As a consequence of intensive studies in multiple areas over many years, much has been learned. A key role of members of this superfamily in normal functioning of the immune system, autoimmunity, and other fundamental cellular process by which tumor cells develop has been established. Many novel mechanisms involving TNF superfamily members in the disease development process have been defined, and a unified concept and new perspectives have also emerged. For example, abrasions in the innate immune system, so far not considered critical in autoimmunity, have found increasing attention, and TNF-directed and not antigen directed therapy has emerged as the most impressive therapeutic advance in managing autoimmunity in humans. These findings provide a foundation for novel drug design efforts that are poised to utilize newly acquired knowledge. Several of these strategies have already materialized into successful therapeutics such as use of TNF for cancers and anti-TNFa antibodies and TNFR-Fc for autoimmune diseases, and many have advanced to human clinical trials, while many more are still being tested in preclinical settings. As in other rapidly evolving fields, these advances are not necessarily congruent and are often difficult to organize into a cogent whole. The aim of Therapeutic Targets of the TNF Superfamily is to make readily available the major research important in the exploitation of this family for developing therapeutic strategies for human diseases, in a single volume. In this volume, a number of leading scientists in the field cover many aspects of biology of TNF superfamily members, ranging from the cloning and characterization of TNF ligands and their receptors, through the use of animal models to study their functions in vivo and their exploitation for human therapeutic use. Each chapter also includes relevant background information and provides useful bibliography for a more detailed analysis, making the study of TNF ligands/receptors accessible at all levels of expertise. This volume presents the state-of-the art account on the role of TNF superfamily members in the pathogenesis and their use in current intervention of cancers and autoimmune disease. This text will be highly valuable for investigators to understand the disease processes regulated by TNF superfamily members and to develop effective therapeutics. A view into the future, inspired by the comprehensive work presented in this volume, predicts that researchers studying TNF superfamily members will continue to make rapid progress in identifying relevant components to the disease process and new therapeutic strategies to target many human diseases including cancers, autoimmune disease and others.

免疫系统调控与疾病治疗:靶向细胞因子网络的新策略 图书名称: 免疫系统调控与疾病治疗:靶向细胞因子网络的新策略 简介: 本书全面深入地探讨了人体免疫系统的复杂调控机制,特别聚焦于细胞因子网络在生理稳态维持以及多种疾病发生发展中所扮演的关键角色。本书旨在为免疫学研究人员、临床医生以及生物制药领域的专业人士提供一个前沿且实用的参考框架,以理解如何通过精准干预细胞因子信号通路,开发出更有效、副作用更小的治疗策略。 第一部分:免疫系统调控的基石——细胞因子信号通路解析 本部分从分子层面详细剖析了免疫细胞间通讯的核心工具——细胞因子。首先,我们系统梳理了细胞因子的分类(如白细胞介素、干扰素、趋化因子及生长因子等),阐述了它们的多效性(Pleiotropy)和冗余性(Redundancy),解释了这些特性如何赋予免疫系统强大的适应性和反应灵活性。 随后,本书深入介绍了细胞因子信号传导的分子机制。重点讲解了细胞因子受体家族(如I型和II型细胞因子受体、趋化因子受体及TNF受体超家族成员)的结构特性,以及下游信号转导通路,特别是JAK-STAT通路、MAPK通路和NF-$kappa$B通路的激活、负反馈调控和跨细胞的信号串扰。我们特别关注了信号转导中的“动态平衡”:如何通过蛋白酪氨酸磷酸酶(PTPs)、去泛素化酶以及特异性抑制因子(如SOCS家族蛋白)来精确地“刹车”信号,维持组织稳态。 此外,本部分也涵盖了细胞因子在免疫细胞发育和分化过程中的作用,例如T细胞(Th1/Th2/Th17/Treg)、B细胞以及先天免疫细胞(如巨噬细胞和树突状细胞)的表型决定和功能极化。对这些基础机制的深入理解,是设计精准靶向疗法的逻辑起点。 第二部分:炎症性疾病的细胞因子驱动力 本部分将理论知识应用于临床实践,详细剖析了细胞因子在几种主要慢性炎症性疾病中的致病机制。 类风湿性关节炎(RA)与关节病变: 我们着重分析了白介素-6 (IL-6)、白介素-1 (IL-1) 和肿瘤坏死因子(TNF)在滑膜炎、软骨破坏和骨侵蚀中的级联效应。本书探讨了如何通过阻断这些关键细胞因子的生物学活性,实现对疾病进程的有效控制,并评估了不同靶向药物的临床效能和耐受性差异。 炎症性肠病(IBD): 详细区分了克罗恩病(CD)和溃疡性结肠炎(UC)中异常激活的免疫回路。重点讨论了Th1/Th17细胞分泌的细胞因子(如IL-12, IL-23, IFN-$gamma$)在肠道黏膜屏障损伤中的作用。此外,我们还探讨了肠道微生物群如何通过介导固有免疫细胞的活化,间接影响细胞因子分泌,从而驱动慢性炎症。 银屑病与慢性皮肤炎症: 聚焦于IL-23/Th17轴在角质形成细胞过度增殖和炎症浸润中的核心地位。本书分析了针对该轴线上关键信号分子(如IL-17A, IL-23p19)的靶向抑制剂如何重塑皮肤免疫微环境,恢复正常角化过程。 第三部分:癌症免疫治疗的新前沿——细胞因子与肿瘤微环境 在肿瘤学领域,细胞因子调控着肿瘤的发生、进展以及免疫逃逸。本部分深入探讨了肿瘤微环境(TME)中复杂的细胞因子“对话”。 免疫抑制性细胞因子网络: 详细描述了转化生长因子-$eta$ (TGF-$eta$) 和白介素-10 (IL-10) 如何促进调节性T细胞(Tregs)的扩增和功能,以及对细胞毒性T淋巴细胞(CTLs)的抑制作用。我们分析了肿瘤细胞分泌的趋化因子如何招募骨髓源性抑制细胞(MDSCs)和肿瘤相关巨噬细胞(TAMs),以及这些细胞如何利用细胞因子分泌(如PD-L1上调)建立免疫豁免区。 肿瘤免疫治疗的协同策略: 本书超越了传统的免疫检查点抑制剂(如PD-1/PD-L1单抗),探讨了如何通过靶向细胞因子信号来增强免疫治疗的响应率。例如,如何利用IL-2/IL-15家族激动剂来促进CTL和NK细胞的活化和持久性;或者如何通过中和特定的促炎细胞因子来降低免疫相关不良事件(irAEs)。 第四部分:自身免疫性疾病的精准干预与未来展望 自身免疫性疾病是由于免疫系统对自身抗原的过度反应所致,其核心驱动力往往是特定的病理性细胞因子。 系统性红斑狼疮(SLE)与干扰素信号: 本部分集中分析了I型干扰素(IFN)签名在SLE发病机制中的重要性,以及靶向IFN受体或下游通路在改善患者临床指标中的潜力。 多发性硬化症(MS): 探讨了髓鞘损伤与T细胞介导的炎症之间的关系,重点分析了趋化因子如何引导淋巴细胞浸润中枢神经系统,以及靶向特定白介素(如IL-17, IL-2)在临床试验中的成果和挑战。 未来展望与技术前沿: 本书的最后一部分展望了下一代细胞因子靶向策略。这包括开发新型的细胞因子模拟物和拮抗剂、利用PROTAC技术降解关键信号蛋白、利用mRNA技术精确递送细胞因子调节因子,以及利用单细胞多组学技术来实时解析复杂疾病中的细胞因子动态变化。本书强调,未来的成功将依赖于对不同组织微环境中细胞因子作用的精细解耦和高度特异性的分子干预。

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