Human
malignant pleural mesothelioma (HMPM) is highly resistant to conventional
therapy, and therefore novel
therapies are required. We previously reported that overexpression of the
FUSE-binding protein-interacting repressor (FIR), a c-myc transcriptional repressor, induces apoptosis via c-Myc suppression, and is thus a suitable
cancer therapy. In the current preclinical trial, a fusion gene deleted non-transmissible Sendai virus vector encoding FIR (SeV/ΔF/FIR) was prepared and its cytotoxic activity against an orthotopic xenograft model of HMPM, in combination with
cisplatin, was assessed. SeV/ΔF/FIR and a fusion gene deleted non-transmissible Sendai virus vector encoding
green fluorescent protein (SeV/ΔF/GFP) were prepared. The transduction efficiency of these agents in terms of dose-dependent cytotoxicity and/or apoptosis induction was then assessed in a few HMPM cells. Combination
therapy with SeV/ΔF/FIR plus
cisplatin was evaluated in vitro and in a mouse model. SeV/ΔF/FIR significantly reduced cell viability in three HMPM cell lines but was less effective in non-
tumor immortalized mesothelial cells. SeV/ΔF/FIR cytotoxicity was partly due to apoptosis induction via c-Myc suppression. In addition, SeV/ΔF/FIR showed synergistic antitumor effects in combination with
cisplatin, as was revealed by isobologram analysis in MSTO-211H. Moreover, combination
therapy with SeV/ΔF/FIR plus
cisplatin demonstrated significant
tumor reduction and improvement in survival rate in an animal model. Combination
therapy with SeV/ΔF/FIR plus
cisplatin has therapeutic potential against HMPM. SeV/ΔF/FIR plus
cisplatin will be an attractive modality against HMPM in the future.