1. Duocarmycin-based antibody–drug conjugates as an emerging biotherapeutic entity for targeted cancer therapy: Pharmaceutical strategy and clinical progress.
- Author
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Yao, Hang-Ping, Zhao, Hui, Hudson, Rachel, Tong, Xiang-Min, and Wang, Ming-Hai
- Subjects
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ANTIBODY-drug conjugates , *TARGETED drug delivery , *CANCER treatment - Abstract
• Duocarmycins and analogues are DNA-alkylators highly cytotoxic to cancer cells. • Up to now, none of duocarmycins have not been approved for oncological practice. • Novel features make duocarmycins an ideal payload for targeted drug delivery. • Various duocarmycin-based antibody-drug conjugates are in clinical development. • An emerging era of duocarmycin-based anticancer biotherapeutics is in the horizon. Duocarmycins are a class of DNA minor-groove-binding alkylating molecules. For the past decade, various duocarmycin analogues have been used as payloads in the development of antibody–drug conjugates (ADCs). Currently, more than 15 duocarmycin-based ADCs have been studied preclinically, and some of them such as SYD985 have been granted Fast-Track Designation status. Nevertheless, progress in duocarmycin-based ADCs also faces challenges, with setbacks including the termination of BMS-936561/MDX-1203. In this review, we discuss issues associated with the efficacy, pharmacokinetic profile, and toxicological activity of these biotherapeutics. Furthermore, we summarize the latest advances in duocarmycin-based ADCs that have different target specificities and linker chemistries. Evidence from preclinical and clinical studies has indicated that duocarmycin-based ADCs are promising biotherapeutics for oncological application in the future. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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