Abstract

Dual Targeting Antibody-Drug Conjugates (ADCs) – Tumors and Their Vasculature

Dimiter Stanchev Dimitrov, Professor, University of Pittsburgh

The speaker will overview ADCs and discuss promising strategies. Targeting the tumor vasculature with ADCs is one such promising anti-cancer strategy.  Dr Dimiter demonstrated an ADC-MMAE targeting CD276 destroyed CD276-positive cancer cells, but was ineffective against tumor vasculature.  In contrast, pyrrolobenzodiazepine-conjugated CD276-ADC killed both cancer cells and tumor vasculature, eradicating large established tumors and metastases, and improving long-term overall survival. CD276 targeted dual-compartment ablation could aid in development of highly selective broad-acting anti-cancer therapies (Seaman S et al. Cancer Cell. 2017 Apr 10;31(4):501-515). Data for ADCs targeting other cancer-related molecules will be also discussed.