Zheng Su, Dian Xiao, Fei Xie, Lianqi Liu, Yanming Wang, Shiyong Fan, Xinbo Zhou, Song Li. Antibody-drug conjugates: Recent advances in linker chemistry[J]. Acta Pharmaceutica Sinica B, 2021, 11(12): 3889-3907

Antibody-drug conjugates: Recent advances in linker chemistry
Zheng Sua,b, Dian Xiaob, Fei Xieb, Lianqi Liub, Yanming Wangb, Shiyong Fanb, Xinbo Zhoub, Song Lia,b
a. School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, China;
b. National Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China
Antibody–drug conjugates (ADCs) are gradually revolutionizing clinical cancer therapy. The antibody–drug conjugate linker molecule determines both the efficacy and the adverse effects, and so has a major influence on the fate of ADCs. An ideal linker should be stable in the circulatory system and release the cytotoxic payload specifically in the tumor. However, existing linkers often release payloads nonspecifically and inevitably lead to off-target toxicity. This defect is becoming an increasingly important factor that restricts the development of ADCs. The pursuit of ADCs with optimal therapeutic windows has resulted in remarkable progress in the discovery and development of novel linkers. The present review summarizes the advance of the chemical trigger, linker-antibody attachment and linker-payload attachment over the last 5 years, and describes the ADMET properties of ADCs. This work also helps clarify future developmental directions for the linkers.
Key words:    Antibody–drug conjugate    Linker    Chemical trigger    Linker-antibody attachment    Linker-payload attachment   
Received: 2021-01-18     Revised: 2021-03-17
DOI: 10.1016/j.apsb.2021.03.042
Funds: This work was funded by the Chinese National Natural Science Foundation (Grant Nos. 81872736 and 81903451), and the China Postdoctoral Science Foundation (Grant No. 2019M664015).
Corresponding author: Shiyong Fan,;Xinbo Zhou,;
Author description:
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Zheng Su
Dian Xiao
Fei Xie
Lianqi Liu
Yanming Wang
Shiyong Fan
Xinbo Zhou
Song Li

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