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特刊前言:“下一代抗体药物偶联物的新兴策略、技术和方法”

Preface for special issue: "Emerging strategies, technologies, and approaches for the next generation ADCs".

作者信息

Walles Markus, Xu Keyang

机构信息

Pharmacokinetic Sciences, Biomedical Research, Novartis, Basel, Switzerland.

BioAnalytical Sciences, Genentech Inc, South San Francisco, CA, USA.

出版信息

Xenobiotica. 2024 Aug;54(8):439-441. doi: 10.1080/00498254.2024.2386407. Epub 2024 Sep 27.

DOI:10.1080/00498254.2024.2386407
PMID:39073838
Abstract

1. Antibody-drug conjugates (ADCs) represent an advanced category of biotherapeutic agents, typically consisting of an antibody bound to a biologically-active cytotoxic agent. Since the first ADC, Mylotarg, was approved in 2000, there have been fifteen ADCs sanctioned to date, with thirteen receiving approval from the FDA for the treatment of a variety of cancers, including blood malignancies and solid tumors. 2. In this Special Issue of Xenobiotica focusing on ADCs, our goal is to compile a collection of papers, featuring both original research and review articles authored by specialists in academia and the pharmaceutical industry, to showcase some of the historical insights gained, current progress, and future prospects to enhance comprehension and tackle obstacles in the field of ADC development for cancer therapy. 3. This special issue features articles that evaluate key components of ADC development, including payload design, innovative linker chemistries, and the use of new technologies for site-specific conjugations beyond traditional engineered cysteines. It also spotlights cutting-edge ADC structures like bispecific ADCs, dual-payload ADCs, targeted nanoparticles and antibody oligonucleotide conjugates (AOCs). 4. Several other papers discuss bioanalytical and ADME strategies for ADCs as well. In addition, approaches to improve the translation of pharmacokinetics, safety, and therapeutic index (TI) of ADCs are presented.

摘要
  1. 抗体药物偶联物(ADCs)是一类先进的生物治疗药物,通常由与生物活性细胞毒性药物结合的抗体组成。自2000年首个ADC药物麦罗塔(Mylotarg)获批以来,截至目前已有15种ADC药物获得批准,其中13种获得美国食品药品监督管理局(FDA)批准用于治疗多种癌症,包括血液系统恶性肿瘤和实体瘤。2. 在这本聚焦于ADCs的《异生物质》特刊中,我们的目标是汇编一系列论文,既有原创研究论文,也有来自学术界和制药行业专家撰写的综述文章,以展示在ADC癌症治疗研发领域所获得的一些历史见解、当前进展以及未来前景,从而增进对该领域的理解并克服其中的障碍。3. 本期特刊的文章评估了ADC研发的关键组成部分,包括载荷设计、创新的连接子化学以及除传统工程化半胱氨酸之外用于位点特异性偶联的新技术的应用。它还聚焦于前沿的ADC结构,如双特异性ADC、双载荷ADC、靶向纳米颗粒和抗体寡核苷酸偶联物(AOCs)。4. 其他几篇论文也讨论了ADC的生物分析和药物代谢动力学及药物处置(ADME)策略。此外,还介绍了改善ADC药物代谢动力学、安全性和治疗指数(TI)转化的方法。

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