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Antibody-Drug Conjugates: Possibilities and Challenges

机译:抗体-药物结合物:可能性和挑战

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摘要

The design of Antibody Drug Conjugates (ADCs) as efficient targeting agents for tumor cell is still in its infancy for clinical applications. This approach incorporates the antibody specificity and cell killing activity of chemically conjugated cytotoxic agents. Antibody in ADC structure acts as a targeting agent and a nanoscale carrier to deliver a therapeutic dose of cytotoxic cargo into desired tumor cells. Early ADCs encountered major obstacles including, low blood residency time, low penetration capacity to tumor microenvironment, low payload potency, immunogenicity, unusual off-target toxicity, drug resistance, and the lack of stable linkage in blood circulation. Although extensive studies have been conducted to overcome these issues, the ADCs based therapies are still far from having high-efficient clinical outcomes. This review outlines the key characteristics of ADCs including tumor marker, antibody, cytotoxic payload, and linkage strategy with a focus on technical improvement and some future trends in the pipeline.
机译:作为肿瘤细胞有效靶向剂的抗体药物缀合物(ADC)的设计仍处于临床应用初期。该方法结合了化学缀合的细胞毒剂的抗体特异性和细胞杀伤活性。 ADC结构中的抗体充当靶向剂和纳米级载体,以将治疗剂量的细胞毒性货物递送到所需的肿瘤细胞中。早期的ADC遇到主要障碍,包括血液停留时间短,对肿瘤微环境的渗透能力低,有效载荷效力低,免疫原性,异常的脱靶毒性,耐药性以及血液循环中缺乏稳定的联系。尽管已进行了广泛的研究来克服这些问题,但基于ADC的疗法仍远未达到高效的临床效果。这篇综述概述了ADC的关键特征,包括肿瘤标志物,抗体,细胞毒性有效载荷和连锁策略,重点是技术改进和开发中的一些未来趋势。

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