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 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.


CONCLUSIONS
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.
Kawano
Hirokazu
H
Division of Gene Therapy Science, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan. hkawano@anges-mg.com
Komaba
Shintarou
S
Kanamori
Toshihide
T
Kaneda
Yasufumi
Y
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001761:Bleomycin / Q000008:administration & dosage; D002945:Cisplatin / Q000008:administration & dosage; D003110:Colonic Neoplasms / Q000628:therapy*; D003713:Dendritic Cells / Q000187:drug effects; D004359:Drug Therapy, Combination; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D050130:Oncolytic Virotherapy / Q000379:methods*; D029082:Sendai virus / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects; D014407:Tumor Cells, Cultured; D038301:Virus Inactivation
D000970:Antineoplastic Agents; D001761:Bleomycin; D002945:Cisplatin