RE:RE:RE:AstraZeneca's ADC disappoints - on severe adverse eventsNovember 27, 2023 - Experts caution that there are challenges with ADCs that still need to be overcome, including toxicities and the tumor microenvironment itself.
Nathan Tumey, associate professor at the School of Pharmacy and Pharmaceutical Sciences at Binghamton University, said there are still a lot of questions about what drives ADC toxicity. Previously, it was believed that the main driver was premature payload release, but he said this is no longer considered the main or only issue.
“Even very, very stable ADCs have toxicity problems,” Tumey said. “Developing an understanding of the molecular basis for ADC toxicity would be a major step forward.”
Senior biotech analyst at Piper Sandler & Co. Joe Catanzaro added that another challenge is the limited number of tumor-specific antigens in solid tumors. Due to the heterogeneity of solid tumors, ADCs have limited tumor targets that can be effected, like in advanced or metasttic breast cancer. (mBC) which is significantly hetergeneous, for example, and prone to tumor escape/ cancer treatment relapse.
https://www.biospace.com/article/next-generation-adcs-aim-to-overcome-toxicities-payload-problems-/