Cancer immunotherapy using the Fusion gene of Sendai virus

Abstract

Inactivated Sendai virus particle (or hemagglutinating virus of Japan envelope; HVJ-E) has been previously reported to possess antitumour properties that activate antitumour immunity. Two glycoproteins, fusion (F) and hemagglutinin-neuraminidase (HN), are present on the surface of HVJ-E. HN is necessary for binding to receptors such as acidic gangliosides, and F induces membrane fusion by associating with membrane lipids. We previously reported that liposomes reconstituted with F but not HN showed antitumour activity by inducing IL-6 secretion in dendritic cells (DCs), suggesting that F protein is capable of eliciting antitumour activity. Here, we attempted to deliver F gene into tumour tissue in mice by electroporation and demonstrated that F gene therapy retarded tumour growth, increased CD4+ and CD8+ T-cell infiltration into tumours and induced tumour-specific IFN-γ T-cell response. However, neutralisation of IL-6R signalling did not impact F plasmid-mediated antitumour effect. Instead, we found that F plasmid treatment resulted in a significant increase in the secretion of the chemokine RANTES (regulated upon activation, normal T cell expressed and secreted) by tumour-infiltrating T cells. Neutralising antibody against RANTES abolished the antitumour effect of F plasmid treatment in a dose-dependent manner. Thus, F gene therapy may show promise as a novel therapeutic for single or combined cancer immunotherapy.

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Acknowledgements

We thank Kotaro Saga for providing the pCY4B and pCY4B-F plasmids. The authors received donations from Ishihara Sangyo Kaisha, Ltd. and Stemrim, Inc. for the research of this article.

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Correspondence to Yasufumi Kaneda.

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