Natural products have been used for many medicinal purposes for centuries. Antibody drug conjugates (ADCs) have utilized this rich source of small molecule therapeutics to produce several clinically useful treatments. ADCs based on the natural product maytansine have been successful clinically. The authors further the utility of the anti-cancer natural product maytansine by developing efficacious payloads and linker-payloads for conjugating to antibodies. The success of our approach was realized in the EGFRvIII targeting ADC EGFRvIII-16. The ADC was able to regress tumors in 2 tumor models (U251/EGFRvIII and MMT/EGFRvIII). When compared to a positive control ADC, the efficacy observed was similar or improved while the isotype control ADCs had no effect.

几个世纪以来，天然产物已用于许多医学目的。抗体药物偶联物（ADC）已利用这种丰富的小分子疗法来源来产生几种临床上有用的疗法。基于天然产物美登素的ADC在临床上已经成功。作者通过开发有效的有效载荷和接头有效载荷来缀合抗体，进一步提高了抗癌天然产物美登素的实用性。我们的方法的成功是在靶向ADC EGFRvIII-16的EGFRvIII中实现的。ADC能够使2种肿瘤模型（U251 / EGFRvIII和MMT / EGFRvIII）中的肿瘤消退。当与阳性对照ADC进行比较时，观察到的功效相似或有所提高，而同型对照ADC则没有效果。