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Cancer immunotherapy using the Fusion gene of Sendai virus

Cancer Gene Therapy volume 27, pages 498–508 (2020)Cite this article

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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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Authors and Affiliations

  1. Division of Gene Therapy Science, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita, Osaka, 565-0871, Japan

    Jiayu A. Tai & Yasufumi Kaneda

  2. Department of Device Application for Molecular Therapeutics, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita, Osaka, 565-0871, Japan

    Chin Yang Chang & Tomoyuki Nishikawa

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  1. Jiayu A. Tai
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Correspondence to Yasufumi Kaneda.

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Tai, J.A., Chang, C.Y., Nishikawa, T. et al. Cancer immunotherapy using the Fusion gene of Sendai virus. Cancer Gene Ther 27, 498–508 (2020). https://doi.org/10.1038/s41417-019-0126-6

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