Imaging-Guided Therapy Simultaneously Targeting HER2 and EpCAM with Trastuzumab and EpCAM-Directed Toxin Provides Additive Effect in Ovarian Cancer Model

Efficient treatment of disseminated ovarian cancer (OC) is challenging due to its heterogeneity and chemoresistance. Overexpression human epidermal growth factor receptor 2 (HER2) epithelial cell adhesion molecule (EpCAM) in approx. 30% 70% cancers, respectively, allows for co-targeted treatment. The clinical efficacy the monoclonal antibody trastuzumab patients with HER2-positive breast, gastric gastroesophageal cancers makes it readily available as HER2-targeting component. As EpCAM-targeting component, we investigated designed ankyrin repeat protein (DARPin) Ec1 fused a truncated variant Pseudomonas exotoxin A reduced immunogenicity low general toxicity (LoPE). Ec1-LoPE was radiolabeled, evaluated cells vitro biodistribution tumor-targeting properties were studied vivo. therapeutic alone combination mice bearing EpCAM- HER2-expressing SKOV3 xenografts. SPECT/CT imaging enabled visualization EpCAM HER2 expression tumors. Co-treatment using more effective at reducing tumor prolonged median survival compared control monotherapy groups. Repeated administration well tolerated without signs hepatic or kidney toxicity. might be potential strategy HER2- EpCAM-positive OC.