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海洋抗体-药物偶联物:设计策略与研究进展

Marine Antibody-Drug Conjugates: Design Strategies and Research Progress.

作者信息

Wang Yu-Jie, Li Yu-Yan, Liu Xiao-Yu, Lu Xiao-Ling, Cao Xin, Jiao Bing-Hua

机构信息

Department of Biochemistry and Molecular Biology, Second Military Medical University, Shanghai 200433, China.

Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China.

出版信息

Mar Drugs. 2017 Jan 13;15(1):18. doi: 10.3390/md15010018.

Abstract

Antibody-drug conjugates (ADCs), constructed with monoclonal antibodies (mAbs), linkers, and natural cytotoxins, are innovative drugs developed for oncotherapy. Owing to the distinctive advantages of both chemotherapy drugs and antibody drugs, ADCs have obtained enormous success during the past several years. The development of highly specific antibodies, novel marine toxins' applications, and innovative linker technologies all accelerate the rapid R&D of ADCs. Meanwhile, some challenges remain to be solved for future ADCs. For instance, varieties of site-specific conjugation have been proposed for solving the inhomogeneity of DARs (Drug Antibody Ratios). In this review, the usages of various natural toxins, especially marine cytotoxins, and the development strategies for ADCs in the past decade are summarized. Representative ADCs with marine cytotoxins in the pipeline are introduced and characterized with their new features, while perspective comments for future ADCs are proposed.

摘要

抗体药物偶联物(ADCs)由单克隆抗体(mAbs)、连接子和天然细胞毒素构建而成,是为肿瘤治疗开发的创新药物。由于兼具化疗药物和抗体药物的独特优势,ADCs在过去几年取得了巨大成功。高特异性抗体的开发、新型海洋毒素的应用以及创新连接子技术都加速了ADCs的快速研发。与此同时,未来的ADCs仍有一些挑战有待解决。例如,为解决药物抗体比(DARs)的不均一性,已提出了多种位点特异性偶联方法。在本综述中,总结了各种天然毒素,特别是海洋细胞毒素的用途,以及过去十年中ADCs的开发策略。介绍了正在研发的具有海洋细胞毒素的代表性ADCs,并对其新特性进行了表征,同时对未来的ADCs提出了前瞻性评论。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f73/5295238/5afc22ab86dd/marinedrugs-15-00018-g001.jpg

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