Cancer immunotherapy using the Fusion gene of Sendai virus
| Autor: | Jiayu A. Tai, Yasufumi Kaneda, Chin Yang Chang, Tomoyuki Nishikawa |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Cancer Research Chemokine T cell T-Lymphocytes Melanoma Experimental Transfection Sendai virus Virus Fusion gene 03 medical and health sciences Mice 0302 clinical medicine Lymphocytes Tumor-Infiltrating medicine Animals Secretion Molecular Biology biology Chemistry Electroporation biology.organism_classification Molecular biology Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis biology.protein Molecular Medicine Female Immunotherapy Gene Fusion CD8 Plasmids |
| Zdroj: | Cancer gene therapy. 27(6) |
| ISSN: | 1476-5500 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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