Design, synthesis and evaluation of anti-CD38 antibody drug conjugate based on Daratumumab and maytansinoid

基于达雷木单抗和美登木素的抗CD38抗体药物偶联物的设计、合成及评价

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作者:Xinfu Zhang, Chengxiang Zhang, Xiaomei Yang, Xucheng Hou, Weiyu Zhao, Don Benson, Jianhua Yu, Yizhou Dong

Abstract

Daratumumab, an FDA approved antibody drug, displays specific targeting ability to abnormal white blood cells overexpressing CD38 and provides efficacious therapy for multiple myeloma. Here, in order to achieve enhanced remission of multiple myeloma, we designed Dara-DM4, antibody drug conjugates (ADCs) by conjugating Daratumumab and DM4 via a disulfide linker. Dara-DM4 showed significantly higher cellular uptake and inhibitory efficacy on MM1S cells that overexpressing CD38 with an IC50 of 0.88 µg/mL post 72 hr treatment. These results support a promising ADCs strategy for multiple myeloma treatment.

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