康普瑞汀 A4 衍生的载药用于抗体药物偶联物。
Combretastatin A4-derived payloads for antibody-drug conjugates.
机构信息
Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, 393 Middle Huaxia Road, Pudong, Shanghai, 201210, China; University of Chinese Academy of Sciences, 19A Yuquan Road, Shijingshan District, Beijing, 100049, China.
Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, 393 Middle Huaxia Road, Pudong, Shanghai, 201210, China.
出版信息
Eur J Med Chem. 2021 Apr 15;216:113355. doi: 10.1016/j.ejmech.2021.113355. Epub 2021 Mar 6.
We describe the use of natural product combretastatin A4 (CA4) as a versatile new payload for the construction of antibody-drug conjugates (ADCs). Cetuximab conjugates consisting of CA4 derivatives were site-specially prepared by disulfide re-bridging approach using cleavable and non-cleavable linkers. These ADCs retained antigen binding and internalization efficiency and exhibited high potencies against cancer cell lines in vitro. The conjugates also demonstrated significant antitumor activities in EGFR-positive xenograft models without observed toxicities. CA4 appears to be a viable payload option for ADCs research and development.
我们描述了使用天然产物 combretastatin A4（CA4）作为构建抗体药物偶联物（ADC）的新型有效载荷的用途。使用可裂解和不可裂解接头通过二硫键重新桥接方法，位点特异性制备了包含 CA4 衍生物的西妥昔单抗缀合物。这些 ADC 保留了抗原结合和内化效率，并在体外对癌细胞系表现出高效力。缀合物在没有观察到毒性的情况下，在 EGFR 阳性异种移植模型中也显示出显著的抗肿瘤活性。CA4 似乎是 ADC 研发的可行有效载荷选择。
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