A new therapy for highly effective tumor eradication using HVJ-E combined with chemotherapy
1 Division of Gene Therapy Science, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan
2 GenomIdea Inc., 7-7-15 Saito-Asagi, Ibaraki, Osaka 567-0085, Japan
BMC Medicine 2007, 5:28 doi:10.1186/1741-7015-5-28Published: 21 September 2007
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.
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.
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 re-challenged 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.
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.