Shalom D Goldberg, Tero Satomaa, Olulanu Aina, Olli Aitio, Krista Burke, Vadim Dudkin, Brian Geist, Onyi Irrechukwu, Anna-Liisa Hänninen, Annamari Heiskanen, Jari Helin, Jukka O Hiltunen, Jacqueline Kinyamu-Akunda, Donna M Klein, Neeraj Kohli, Titta Kotiranta, Tuula Lähteenmäki, Ritva Niemelä, Virve Pitkänen, Henna Pynnönen, William Rittase, Kristen Wiley, Junguo Zhou, Juhani Saarinen
PURPOSE: Antibody-drug conjugates (ADCs) have shown impressive clinical activity with approval of many agents in hematological and solid tumors. However, challenges remain with both efficacy and safety of ADCs. This study describes novel trastuzumab-auristatin conjugates with the hydrophilic MMAE prodrug MMAU, and optimization of a glycopeptide linker leading to a wider therapeutic window. EXPERIMENTAL DESIGN: Trastuzumab was conjugated with auristatin payloads via a series of linkers using a stabilized maleimide handle...
February 7, 2024: Molecular Cancer Therapeutics