Antibody drug conjugates as targeted cancer therapy: past development, present challenges and future opportunities

IF 6.9 3区 医学 Q1 CHEMISTRY, MEDICINAL Archives of Pharmacal Research Pub Date : 2023-04-18 DOI:10.1007/s12272-023-01447-0
Ritwik Maiti, Bhumika Patel, Nrupesh Patel, Mehul Patel, Alkesh Patel, Nirav Dhanesha
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引用次数: 2

Abstract

Antibody drug conjugates (ADCs) are promising cancer therapeutics with minimal toxicity as compared to small cytotoxic molecules alone and have shown the evidence to overcome resistance against tumor and prevent relapse of cancer. The ADC has a potential to change the paradigm of cancer chemotherapeutic treatment. At present, 13 ADCs have been approved by USFDA for the treatment of various types of solid tumor and haematological malignancies. This review covers the three structural components of an ADC—antibody, linker, and cytotoxic payload—along with their respective structure, chemistry, mechanism of action, and influence on the activity of ADCs. It covers comprehensive insight on structural role of linker towards efficacy, stability & toxicity of ADCs, different types of linkers & various conjugation techniques. A brief overview of various analytical techniques used for the qualitative and quantitative analysis of ADC is summarized. The current challenges of ADCs, such as heterogeneity, bystander effect, protein aggregation, inefficient internalization or poor penetration into tumor cells, narrow therapeutic index, emergence of resistance, etc., are outlined along with recent advances and future opportunities for the development of more promising next-generation ADCs.

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抗体药物偶联物作为靶向癌症治疗:过去的发展,目前的挑战和未来的机遇
抗体药物偶联物(adc)是一种很有前景的癌症治疗药物,与单独的小细胞毒性分子相比,它的毒性很小,并且已经显示出克服肿瘤耐药性和防止癌症复发的证据。ADC有可能改变癌症化疗治疗的模式。目前,已有13种adc被美国fda批准用于治疗各种类型的实体瘤和血液系统恶性肿瘤。本文综述了adc的三种结构成分——抗体、连接体和细胞毒性有效载荷,以及它们各自的结构、化学、作用机制和对adc活性的影响。它涵盖了对连接器在功效,稳定性和amp方面的结构作用的全面见解;adc、不同类型连接器的毒性;各种共轭技术。简要概述了用于ADC定性和定量分析的各种分析技术。本文概述了adc目前面临的挑战,如异质性、旁观者效应、蛋白质聚集、肿瘤细胞内化效率低或渗透能力差、治疗指数窄、耐药性的出现等,以及更有前景的下一代adc的最新进展和未来发展机遇。
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来源期刊
CiteScore
13.40
自引率
9.00%
发文量
48
审稿时长
3.3 months
期刊介绍: Archives of Pharmacal Research is the official journal of the Pharmaceutical Society of Korea and has been published since 1976. Archives of Pharmacal Research is an interdisciplinary journal devoted to the publication of original scientific research papers and reviews in the fields of drug discovery, drug development, and drug actions with a view to providing fundamental and novel information on drugs and drug candidates.
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