Treatment of experimental pancreatic cancer with 213-Bismuth-labeled chimeric antibody to single-strand DNA

Background: Novel approaches to treatment of pancreatic cancer (PCa) are urgently needed. A chimeric monoclonal antibody (mAb) chTNT3 binds to single-strand DNA (ssDNA) and RNA released from the non-viable cells in fast growing tumors. Here the authors investigated whether radioimmunotherapy (RIT) using chTNT3 mAb radiolabeled with 213-Bismuth (Bi-213) could be effective in treatment of experimental PCa. Methods: Two human PCa cell lines, Panc1 and MiaPaCa-2, were used for in vitro experiments. The xenografts in mice were established using MiaPaCa-2 cells. Therapy compared Bi-213-chTNT3 (700 mu Ci) to gemcitabine or cisplatin, untreated controls and 'cold' chTNT3. Results: RIT abrogated the tumors growth while tumors in control groups grew aggressively. Chemotherapy was less effective than RIT and toxic to mice while RIT did not have any side effects. Conclusions: RIT with Bi-213-chTNT3 was safe and effective in the treatment of experimental PCa in comparison with chemotherapy. This makes alpha-RIT targeting ssDNA a promising modality for further development.