Abstract
BackgroundInactivated 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.MethodsCT-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.ResultsWe 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.ConclusionCombination 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.
Highlights
We recently found that HVJ particles (HVJ-E) itself mediates a powerful anti-tumor effect by enhancing cytokine production in dendritic cells (DCs), generating tumor-specific cytotoxic T cells (CTLs), and inhibiting regulatory T-cell activity [8]
We demonstrated that intra-tumor injection of HVJ-E/BLM combined with systemic administration of cis-diamminedichloroplatinum (II) (CDDP; cisplatin) achieved highly effective tumor eradication by both inducing anti-tumor immunity and delivering anticancer reagent to tumors
After CDDP administration, the body weight of mice treated with CDDP alone or CDDP plus HVJ-E/BLM group decreased transiently, but statistically, no significant difference was seen in the body weight between mice treated with CDDP alone and mice treated with CDDP plus HVJ-E/BLM (Figure 1B)
Summary
Inactivated HVJ (hemagglutinating virus of Japan; Sendai virus) particles 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. Chemotherapy, and radiotherapy have contributed to the successful treatment of cancer, there are still many cases of cancer that are not eradicated by these treatments. Oncolytic viruses have received attention from researchers because of their powerful killing effect on cancer cells [1,2]. The oncolytic viruses have worked very well in animal tumor models. They have been less successful in the treatment of humans [6]. Tumorselective replication of the viruses is not strict enough to prevent viral replication in non-cancerous cells [7], the efficiency of replication is much lower than that in cancer cells
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