Death Ligands Designed to Kill: Development and Application of Targeted Cancer Therapeutics Based on Proapoptotic TNF Family Ligands
Death Ligands Designed to Kill: Development and Application of Targeted Cancer Therapeutics Based on Proapoptotic TNF Family Ligands
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DOI：
10.1007/400_2008_22
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发表时间：
2009-01-01
期刊：
影响因子：
--
通讯作者：
Pfizenmaier, Klaus
中科院分区：
文献类型：
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作者：
Gerspach, Jeannette;Wajant, Harald;Pfizenmaier, Klaus
与癌症发展或进展相关的分子标志物的鉴定开启了治疗学发展的新时代。一些具有靶向作用的低分子量化学品和重组蛋白治疗剂成功引入临床实践，使人们对在总体临床反应和耐受性方面广泛改善癌症治疗寄予厚望。靶向恶性细胞的凋亡机制是对抗癌症的一个有吸引力的概念，目前在临床前和临床开发的各个阶段将其用于TNF配体家族的促凋亡成员。本文综述了近年来肿瘤坏死因子（TNF）、CD95L和肿瘤坏死因子相关凋亡配体（TRAIL）的相关蛋白配体、受体特异性抗体和基因治疗方法在肿瘤坏死因子（TNF）、CD95L和TRAIL死亡受体生物学治疗领域的研究进展。还将讨论基于这些死亡配体的新衍生变体和融合蛋白的临床前数据，这些变体和融合蛋白旨在以肿瘤限制的方式起作用，从而防止系统性的潜在有害作用。
The identification of molecular markers associated with cancer development or progression, opened a new era in the development of therapeutics. The successful introduction of a few low molecular weight chemicals and recombinant protein therapeutics with targeted actions into clinical practice have raised great expectations to broadly improve cancer therapy with respect to both overall clinical responses and tolerability. Targeting the apoptotic machinery of malignant cells is an attractive concept to combat cancer, which is currently exploited for the proapoptotic members of the TNF ligand family at various stages of preclinical and clinical development. This review summarizes recent progress in this rapidly progressing field of "biologic" therapies targeting the death receptors of TNF, CD95L, and TRAIL by means of its cognate protein ligands, receptor specific antibodies, and gene therapeutic approaches. Preclinical data on newly derived variants and fusion proteins based on these death ligands, designed to act in a tumor restricted manner, thereby preventing a systemic, potentially harmful action, will also be discussed.