Efficacy of anti-death receptor 5 (DR5) antibody (TRA-8) against primary human ovarian carcinoma using a novel ex vivo tissue slice model

摘要: Abstract Objectives. The purpose of this study was to evaluate the cytotoxicity a death receptor 5 (DR5) targeting monoclonal antibody (TRA-8) in primary ovarian cancer specimens utilizing tissue slice technique that allows for assessment anti-tumor activity three-dimensional ex vivo model. Methods. Nineteen tumor were obtained at time cytoreductive surgery and slices prepared with Krumdieck slicer. Tumor incubated TRA-8 24 h dose–response curve established each specimen using non-linear modeling, IC 50 values used as parameter sensitivity. In parallel ATP viability assays, treated untreated assessed by immunohistochemistry (IHC) western blot analysis confirm apoptosis induction. Results. Incubation 0–1000 ng/ml resulted dose response maximum killing observed 1000 ng/ml compared control slices. 6.0 >1000 ng/ml calculated individual specimens. H&E, IHC, demonstrated TRA-8-induced cellular dose-dependent fashion via activation caspases 3, 8, 9. produced varying concentrations confirmed TUNEL technique. Treatment markedly reduced proliferation cells measured expression Ki-67/SP6. Conclusions. This demonstrates DR5 decreases proliferation, increases caspase activation, induces novel model cancer.