![]() Valine-citrulline-monomethyl auristatin EĪccording to the World Health Organization, cancer was the second leading cause of death globally in 2018. Succinimidyl 4-(N-maleimidomethyl)cyclohexane-1-carboxylate TCEP,Īdo-trastuzumab emtansine (Kadcyla ®) VCMMAE, Half-maximal inhibitory concentration LDS, Hydrophobic interaction chromatography IC 50, Half-maximal effective concentration ESI, The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Ĭompeting interests: The authors have declared that no competing interests exist. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.ĭata Availability: All relevant data are within the manuscript and its Supporting Information files.įunding: This work was supported by the Ministry of Science and Technology (MOST107-01) and the Program for Translational Innovation of Biopharmaceutical Development–Technology Supporting Platform Axis (AS-KPQ-106-TSPA). Received: AugAccepted: SeptemPublished: September 28, 2020Ĭopyright: © 2020 Chiang et al. Pizzo, Duke University School of Medicine, UNITED STATES (2020) Preparation and characterization of antibody-drug conjugates acting on HER2-positive cancer cells. Our results demonstrated the potential of H32-VCMMAE as a good ADC candidate.Ĭitation: Chiang Z-C, Chiu Y-K, Lee C-C, Hsu N-S, Tsou Y-L, Chen H-S, et al. 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. ![]() 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 efficacy of H32-VCMMAE was in turn better than that of H32-DM1. The anticancer efficacy of H32-DM1 was 2- to 8-fold greater than that of Kadcyla ®. Several H32-VCMMAE ADCs were established with higher DARs and greater synthetic yields without compromising potency. Mass spectrometry, hydrophobic interaction chromatography, polyacrylamide gel electrophoresis, and in vitro cell assays were performed to analyze and optimize the ADCs. Activated functional groups, including an N-hydroxysuccinimidyl (NHS) ester and a maleimide, were utilized to make the ADCs. 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 anti-HER2 antibody H32, which is capable of cell internalization.
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