The ovarian cancer is a heterogeneous and most malignant form of gynecologic cancer. Despite surgical intervention and systemic chemotherapy, treatment options for this cancer remain limited. Antibody–drug conjugate (ADC) represents a novel targeted therapy that uses an antibody to specifically deliver toxins to tumor sites. With the approval of the first ADC targeting ovarian cancer, more ADCs are currently under preclinical investigation or clinical trials to expand therapeutic options. In this study, we developed four ADCs targeting epidermal growth factor receptor (EGFR), epidermal growth factor receptor 2 (Her2), trophoblast cell-surface antigen 2 (Trop2), and tissue factor (TF) that are highly expressed on ovarian cancer cells. Our ADCs are constructed using single chain antibody fragments (scFvs) as the antibody backbone, with the cytotoxic agent monomethyl auristatin E conjugated via SNAP-tag technology, offering a high site-specific conjugation efficiency. All four ADCs preliminarily demonstrated specific binding and internalization, as verified by flow cytometry and fluorescence microscopy. Additionally, the ADCs exhibited potent and specific cytotoxicity in a dose-dependent manner in four ovarian cancer cell lines, inducing apoptosis at nanomolar concentrations. These constructs showed encouraging preliminary characteristics, although further studies are required to validate their therapeutic potential.
Zhang et al. (2026) studied this question.