The development and characterization of a functional monoclonal antibody that shows efficacy in both ovarian and colon xenograft tumor models

710 Functional monoclonal antibodies demonstrating anti-cancer efficacy have demonstrated potential as an alternative to, or in conjunction with, conventional cancer treatment. ARIUS Research Inc. uses a non-traditional method of drug discovery that focuses on anti-cancer activity rather than target affinity and has created a library of functional monoclonal antibodies that demonstrate killing in cancer but not in normal cells in vitro. One of these antibodies, AR6BD-25, was selected for study in vivo based on its in vitro killing of ovarian and colon cancer cell lines, despite the fact that it did not show binding via FACS, ELISA or IHC in preliminary studies. The in vivo efficacy of AR6BD-25 was evaluated in two xenograft models. In the OVCAR-3 xenograft model, increasing body weight due to ascites formation was used as a surrogate measure of tumor progression. At 12 days post-treatment, the weight gain of the AR6BD-25 treated animals was 50% less than control treated animals (p=0.0055). AR6BD-25 has also demonstrated anti-tumor activity in a SW1116 colon preventative tumor xenograft model. Treated animals had a mean tumor volume that was 54% smaller than isotype control treated mice at the end of treatment, p=0.0007. Subsequent characterization of the binding protein revealed that AR6BD-25 binds to a specific protein present in lysates from OVCAR-3 cells. Active identification of this protein antigen is ongoing. AR6BD-25, is a functional antibody that has demonstrated efficacy in models of both human ovarian and colon cancer and would not have been discovered using a traditional approach based on binding as a necessary criteria.