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

By Francisco Velázqueza,* Thomas Nittolib,* Frank Delfinob, Marcus Kellyb, Serena Carossoa, Thomas Markotana, Arthur Kunzb, Zhaoyuan Chenb, Shu Maob, Jing Shanb, Elizabeth Navarrob, Feng Zhaob, Sosina Makonnenb, Carlos Hickeyb, Jan Spinka, William Olsonb, Jessica Kirshnerb, Gavin Thurstonb, Nicholas Papadopoulosb.

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.