54. Combination Therapy Using DR4 and DR5 TRAIL Antibodies, Gemcitabine, and Radiation Inhibits Pancreatic Cancer Growth in an Animal Model

Abstract

Introduction: TRA-8 is a monoclonal TRAIL agonistic antibody with specificity for the DR5 receptor, while 2E12 is an anti-DR4 antibody. Binding of TRA-8 and 2E12 to their respective receptors leads to activation of the death receptor pathway and apoptosis. Both TRA-8 and 2E12 have pro-apoptotic activity both in vitro and in vivo against pancreatic cancer cells, and we have also demonstrated that TRA-8 is a radiation sensitizer. We hypothesized that TRA-8/2E12 combination therapy could significantly enhance induction of apoptosis in vitro and increase the efficacy of gemcitabine and radiation therapy in a pancreatic cancer animal model.