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抗体药物偶联物用于癌症治疗:从金属药物到自然启发载荷

英文原题:Antibody Drug Conjugates for Cancer Therapy: From Metallodrugs to Nature-Inspired Payloads.

查看英文原题

Antibody Drug Conjugates for Cancer Therapy: From Metallodrugs to Nature-Inspired Payloads.

PubMed 2024/08/08(内容时间) Int J Mol Sci Q1 · IF 5.6(JCR 2025)

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中文摘要

本综述重点介绍了配备金属基和自然启发有效载荷的抗体-药物偶联物(ADCs)的重大进展,聚焦于抗体偶联的合成策略。传统方法如马来酰亚胺和琥珀酰亚胺偶联以及经典缩合反应在金属药物和天然化合物中较为普遍。

然而,新兴的非传统策略如光偶联因其更温和的条件以及在最小化副反应方面选择性形成ADC而日益受到关注。本综述还总结了这些ADCs的治疗和诊断特性,强调其相较于非偶联有效载荷在癌症治疗中增强的选择性和减少的副作用。ADCs结合了单克隆抗体的特异性和化疗药物的细胞毒性,提供了一种靶向消除癌细胞同时保护健康组织的方法。这种靶向机制在多种恶性肿瘤中已展现出令人印象深刻的临床疗效。未来的关键进展包括改进连接子技术以增强稳定性和控制细胞毒性剂的释放,引入新型、更强效的细胞毒性剂,以及通过基因组和蛋白质组技术鉴定新的癌症特异性抗原。ADCs也有望在与免疫检查点抑制剂、CAR-T 细胞和小分子抑制剂的联合治疗中发挥关键作用,从而带来更持久且可能治愈的结果。正在进行的研究和临床试验正在扩展其能力,为更有效、更安全、更个性化的治疗铺平道路,使ADCs成为现代医学的基石,并为患者带来新的希望。

展开英文摘要原文

This review highlights significant advancements in antibody-drug conjugates (ADCs) equipped with metal-based and nature-inspired payloads, focusing on synthetic strategies for antibody conjugation. Traditional methods such us maleimide and succinimide conjugation and classical condensation reactions are prevalent for metallodrugs and natural compounds.

However, emerging non-conventional strategies such as photoconjugation are gaining traction due to their milder conditions and, in an aspect which minimizes side reactions, selective formation of ADC. The review also summarizes the therapeutic and diagnostic properties of these ADCs, highlighting their enhanced selectivity and reduced side effects in cancer treatment compared to non-conjugated payloads. ADCs combine the specificity of monoclonal antibodies with the cytotoxicity of chemotherapy drugs, offering a targeted approach to the elimination of cancer cells while sparing healthy tissues. This targeted mechanism has demonstrated impressive clinical efficacy in various malignancies.

Key future advancements include improved linker technology for enhanced stability and controlled release of cytotoxic agents, incorporation of novel, more potent, cytotoxic agents, and the identification of new cancer-specific antigens through genomic and proteomic technologies.

ADCs are also expected to play a crucial role in combination therapies with immune checkpoint inhibitors, CAR-T cells, and small molecule inhibitors, leading to more durable and potentially curative outcomes. Ongoing research and clinical trials are expanding their capabilities, paving the way for more effective, safer, and personalized treatments, positioning ADCs as a cornerstone of modern medicine and offering new hope to patients.

论文信息

作者
Tonon G、Rizzolio F、Visentin F、Scattolin T
第一作者单位
Department of Molecular Sciences and Nanosystems, Università Ca' Foscari Campus Scientifico, Via Torino 155, 30174 Venezia-Mestre, Italy.Italy
通讯作者单位
Dipartimento di Scienze Chimiche, Università degli Studi di Padova, Via Marzolo 1, 35131 Padova, Italy.Italy
文献类型
综述
期刊
International journal of molecular sciences2024 Aug 8
原文标识
PubMed 39201338 · DOI 10.3390/ijms25168651