Antibody Drug Conjugates of Cleavable Amino-alkyl and Aryl Maytansinoids - Abzena

Antibody Drug Conjugates of Cleavable Amino-alkyl and Aryl Maytansinoids

Authors: Thomas Nittolia, Marcus Kelly, Frank Delfino, John Rudge, Arthur Kunz, Thomas Markotanb, Jan Spink, Zhaoyuan Chena, Jing Shan, Elizabeth Navarro, Michele Tait, Kathleen Provoncha, Jason Giurleo, Feng Zhao, Xiaobo Jiang, Donna Hylton, Sosina Makonnena, Carlos Hickey and Nicholas Papadopoulos

Publication: Bioorganic & Medicinal Chemistry

First published: 15 May 2018

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.

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