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抗体药物偶联物作为新型化疗形式的益处和挑战。

Benefits and challenges of antibody drug conjugates as novel form of chemotherapy.

机构信息

Enzyme and Microbial Biochemistry Laboratory, Department of Chemistry, Indian Institute of Technology Delhi, New Delhi 110016, India.

Enzyme and Microbial Biochemistry Laboratory, Department of Chemistry, Indian Institute of Technology Delhi, New Delhi 110016, India.

出版信息

J Control Release. 2022 Jan;341:555-565. doi: 10.1016/j.jconrel.2021.12.013. Epub 2021 Dec 11.

DOI:10.1016/j.jconrel.2021.12.013
PMID:34906604
Abstract

Antibody drug conjugates (ADCs) are an emerging therapeutic modality for targeted cancer treatment. They represent the unique amalgamation of chemotherapy and immunotherapy. ADCs comprise of monoclonal antibodies linked with drugs (payloads) through a chemical linker designed to deliver the cytotoxic moiety to the cancer cells. The present paper is a review of recent clinical advances of each component of ADCs (antibody/linker/payload) and how the individual component influences the activity of ADCs. The review discusses opportunities for improving ADCs efficiency and ways to have a better antibody-based molecular platform, which could substantially increase chemotherapy outcomes. This review casts an outlook on how ADCs enhancement in terms of their pharmacokinetics, therapeutic indexes and safety profiles can overcome the prevailing challenges like drug resistance in cancer treatment. A novel strategy of augmenting antibodies with nanoparticles anticipates a huge success in terms of targeted delivery of drugs in several diseases. Antibody conjugated nanoparticles (ACNPs) are a very promising strategy for the cutting-edge development of chemo/immunotherapies for efficient delivery of payloads at the targeted cancer cells. The avenues of a high drug to antibody ratio (DAR) owing to the selection of broad chemotherapy payloads, regulating drug release eliciting higher avidity of ACNPs over ADCs will be the modern immunotherapeutics. ACNPs carry immense potential to mark a paradigm shift in cancer chemotherapy that may be a substitute for ADCs.

摘要

抗体药物偶联物 (ADC) 是一种新兴的靶向癌症治疗方法。它们是化疗和免疫疗法的独特结合。ADC 由单克隆抗体与药物(有效载荷)通过化学连接子连接而成,旨在将细胞毒性部分递送到癌细胞中。本文综述了 ADC 的每个组成部分(抗体/连接子/有效载荷)的最新临床进展,以及各个组成部分如何影响 ADC 的活性。讨论了提高 ADC 效率的机会以及如何拥有更好的基于抗体的分子平台,这可以大大提高化疗效果。本文展望了如何通过改善 ADC 的药代动力学、治疗指数和安全性特征来克服癌症治疗中耐药性等普遍挑战。一种通过纳米颗粒增强抗体的新策略预计将在几种疾病的药物靶向递送上取得巨大成功。抗体偶联纳米颗粒 (ACNP) 是开发化学/免疫治疗的一种很有前途的策略,可有效将有效载荷递送至靶向癌细胞。由于选择了广泛的化疗有效载荷,从而实现了高药物与抗体比 (DAR),这将调节药物释放,使 ACNP 对 ADC 的亲和力更高,成为现代免疫疗法。ACNP 具有在癌症化疗中实现范式转变的巨大潜力,可能成为 ADC 的替代品。

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