Identification Of New Classes Of Maytansinoid Payloads For ADCs That Display In Vivo Activity

By Francisco Velázquez ,* Thomas Nittoli ,* Frank Delfino , Marcus Kelly , Serena Carosso , Thomas Markotan , Arthur Kunz , Zhaoyuan Chen , Shu Mao , Jing Shan , Elizabeth Navarro , Feng Zhao , Sosin, Makonnen , Carlos Hickey , Jan Spink , William Olson , Jessica Kirshnerb , Gavin Thurston , Nicholas Papadopoulos.

Developing next-generation Antibody-Drug Conjugates (ADCs) requires designing novel payloads with superior characteristics, such as enhanced cell permeability to achieve a robust "bystander killer effect." This case study details a successful research collaboration focused on advancing ADC payload technology for cancer therapy.

The project centered on designing and synthesizing novel tubulin inhibitors based on the potent maytansine core. Unlike previous designs, the new payloads were engineered for improved cell permeation. The most potent candidates were then attached to cleavable linkers and conjugated to an antibody targeting the ovarian cancer antigen, MUC16. Discover how expert CRO support can accelerate the discovery of customized, high-potency payloads for your complex ADC programs. Learn more about the design strategy and outcomes of this successful partnership.