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

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.

SUBMITTER: Zhang X

PROVIDER: S-EPMC6339845 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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

Zhang Xinfu X Zhang Chengxiang C Yang Xiaomei X Hou Xucheng X Zhao Weiyu W Benson Don D Yu Jianhua J Dong Yizhou Y

Bioorganic & medicinal chemistry 20181216 3

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 IC<sub>50</s ...[more]

PMID: 30594452

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