A new therapy for highly effective tumor eradication using HVJ-E combined with chemotherapy

Background: Inactivated HVJ ( hemagglutinating virus of Japan; Sendai virus) particles (HVJ envelope vector; HVJ- E can incorporate and deliver plasmid DNA, siRNA, antibody and peptide and anti-cancer drugs to cells both in vitro and in vivo. We attempted to eradicate tumors derived from mouse colon cancer cells, CT26, by combining bleomycin ( BLM)-incorporated HVJ- E (HVJ- E/BLM) with cisplatin (CDDP) administration. Methods: CT-26 tumor mass was intradermally established in Balb/c mice. HVJ- E/BLM was directly injected into the tumor mass with or without intraperitoneal administration of CDDP. The anti-tumor effect was evaluated by measuring tumor size and cytotoxic T cell activity against CT26. Re-challenge of tumor cells to treated mice was performed 10 days or 8 months after the initial tumor inoculation. Results: We found that three intratumoral injections of HVJ- E/BLM along with a single intraperitoneal administration of CDDP eradicated CT26 tumors with more than 75% efficiency. When tumor cells were intradermally re-injected on day 10 after the initial tumor inoculation, tumors on both sides disappeared in most of the mice that received the combination therapy of HVJ- E/BLM and CDDP. Eight months after the initial tumor eradication, surviving mice were rechallenged with CT26 cells. The re-challenged tumors were rejected in all of the surviving mice treated with the combination therapy. Cytotoxic T lymphocytes specific for CT26 were generated in these surviving mice. Conclusion: Combination therapy consisting of HVJ-E and chemotherapy completely eradicated the tumor, and generated anti-tumor immunity. The combination therapy could therefore be a promising new strategy for cancer therapy.