基于达雷妥尤单抗和美登素的抗 CD38 抗体药物偶联物的设计、合成与评价。
Design, synthesis and evaluation of anti-CD38 antibody drug conjugate based on Daratumumab and maytansinoid.
机构信息
Division of Pharmaceutics & Pharmaceutical Chemistry, College of Pharmacy, The Ohio State University, Columbus, OH 43210, United States; State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116024, China.
Division of Pharmaceutics & Pharmaceutical Chemistry, College of Pharmacy, The Ohio State University, Columbus, OH 43210, United States.
出版信息
Bioorg Med Chem. 2019 Feb 1;27(3):479-482. doi: 10.1016/j.bmc.2018.12.024. Epub 2018 Dec 16.
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 of 0.88 µg/mL post 72 hr treatment. These results support a promising ADCs strategy for multiple myeloma treatment.
达雷妥尤单抗是一种获得 FDA 批准的抗体药物，对过度表达 CD38 的异常白细胞具有特异性靶向能力，为多发性骨髓瘤提供了有效的治疗方法。在这里，为了实现多发性骨髓瘤的缓解效果增强，我们通过二硫键将达雷妥尤单抗和 DM4 连接起来，设计了抗体药物偶联物（ADC）达雷妥尤单抗-DM4。达雷妥尤单抗-DM4 在 72 小时处理后对过度表达 CD38 的 MM1S 细胞的细胞摄取和抑制效果显著提高，IC 为 0.88μg/mL。这些结果支持了一种有前途的用于多发性骨髓瘤治疗的 ADCs 策略。
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