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Bioproduction of Antibody-Drug Conjugate Payload Precursors by Engineered Cell Factories
Jie Wang1, Han Xiao1, Zhi-Gang Qian1
1State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic and Developmental Sciences, and Laboratory of Molecular Biochemical Engineering and Advanced Fermentation Technology, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, 800 Dong-Chuan Road, Shanghai, 200240, China.
Abstract:
Antibody-drug conjugates (ADCs), which combine the exquisite specificity of antibodies with the cell-killing ability of cytotoxic drug payloads, have emerged as an attractive means for treating cancers. All (pre)clinical ADCs employ biosynthesized cytotoxins as their ADC payload precursors (APPs). The cost-effective bioproduction of APPs is receiving great interest from both academia and industry. Given the lack of systematic overviews of the topic, we provide the current status of APPs and focus on their state-of-the-art bioproduction strategies, illustrated with typical examples and critical analyses. Challenges in further enhancing the bioproduction efficiency of APPs and other cytotoxins are also discussed. This research has implications for bioprocess and metabolic engineering, systems and synthetic biology, and biopharmaceutical drug discovery, development, and industrialization.