Preparation and characterization of antibody-drug conjugates acting on HER2-positive cancer cells

Zu Chian Chiang, Yi Kai Chiu, Cheng Chung Lee, Nai Shu Hsu, Yueh Liang Tsou, Hong Sen Chen, Horng Ru Hsu, Tzung Jie Yang, An Suei Yang, Andrew H.J. Wang

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)


Two systems of antibody-drug conjugates (ADCs), noncleavable H32-DM1 and cleavable H32-VCMMAE, were developed by using different linkers and drugs attached to the antiHER2 antibody H32, which is capable of cell internalization. Activated functional groups, including an N-hydroxysuccinimidyl (NHS) ester and a maleimide, were utilized to make the ADCs. Mass spectrometry, hydrophobic interaction chromatography, polyacrylamide gel electrophoresis, and in vitro cell assays were performed to analyze and optimize the ADCs. Several H32-VCMMAE ADCs were established with higher DARs and greater synthetic yields without compromising potency. The anticancer efficacy of H32-DM1 was 2- to 8-fold greater than that of Kadcyla®. The efficacy of H32-VCMMAE was in turn better than that of H32-DM1. The anticancer efficacy of these ADCs against N87, SK-BR-3 and BT474 cells was in the following order: H32-VCMMAE series > H32-DM1 series > Kadcyla®. The optimal DAR for H32-VCMMAE was found to be 6.6, with desirable attributes including good cell penetration, a releasable payload in cancer cells, and high potency. Our results demonstrated the potential of H32-VCMMAE as a good ADC candidate.

Original languageEnglish
Article numbere0239813
JournalPLoS ONE
Issue number9 September
Publication statusPublished - Sept 2020
Externally publishedYes

ASJC Scopus subject areas

  • General


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