Combretastatin A4-derived payloads for antibody-drug conjugates
Rong Huang1, Yao Sheng2, Zili Xu1
1Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, 393 Middle Huaxia Road, Pudong, Shanghai, 201210, China; University of Chinese Academy of Sciences, 19A Yuquan Road, Shijingshan District, Beijing, 100049, China.
Abstract:
We describe the use of natural product combretastatin A4 (CA4) as a versatile new payload for the construction of antibody-drug conjugates (ADCs). Cetuximab conjugates consisting of CA4 derivatives were site-specially prepared by disulfide re-bridging approach using cleavable and non-cleavable linkers. These ADCs retained antigen binding and internalization efficiency and exhibited high potencies against cancer cell lines in vitro. The conjugates also demonstrated significant antitumor activities in EGFR-positive xenograft models without observed toxicities. CA4 appears to be a viable payload option for ADCs research and development.
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