Anti-tumor activity of TRA-8 anti-death receptor 5 (DR5) monoclonal antibody in combination with chemotherapy and radiation therapy in a cervical cancer modeli

Objectives. There is substantial evidence that tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) causes apoptosis via activation of death receptors 4 and 5 (DR4 and DR5). We sought to determine the therapeutic potential of TRA-8 (anti-DR5 monoclonal antibody) in combination with chemotherapy and radiation therapy in a cervical cancer model. Methods. DR5 expression in 7 human cervical cancer cell lines was analyzed by indirect immunofluorescence using murine TRA-8 in combination with flow cytometry. Cell lines were treated with TRA-8 alone or in combination with cisplatin, topotecan, or radiation, and cytotoxicity assays were performed. Mice were inoculated with ME-180 cancer cells and treated with different combinations of therapy. Animals receiving antibody were injected intraperitoneally with 200 Ag of TRA-8. Animals received 9 Gy 60Co radiation divided into 3 fractions and 3