title: A Kunjin replicon vector encoding granulocyte macrophage colony-stimulating factor for intra-tumoral gene therapy.
abstract: We have recently developed a non-cytopathic RNA replicon-based viral vector system based on the flavivirus Kunjin. Here, we illustrate the utility of the Kunjin replicon system for gene therapy. Intra-tumoral injections of Kunjin replicon virus-like particles encoding granulocyte colony-stimulating factor were able to cure >50% of established subcutaneous CT26 colon carcinoma and B16-OVA melanomas. Regression of CT26 tumours correlated with the induction of anti-cancer CD8 T cells, and treatment of subcutaneous CT26 tumours also resulted in the regression of CT26 lung metastases. Only a few immune-based strategies are able to cure these aggressive tumours once they are of a reasonable size, illustrating the potential of this vector system for intra-tumoral gene therapy applications.
authors.affiliation: Queensland Institute of Medical Research, PO Royal Brisbane Hospital, Brisbane, Queensland, Australia.
authors.forename: D
authors.initials: D
authors.lastname: Hoang-Le
authors.forename: L
authors.initials: L
authors.lastname: Smeenk
authors.forename: I
authors.initials: I
authors.lastname: Anraku
authors.forename: G P
authors.initials: GP
authors.lastname: Pijlman
authors.forename: X J
authors.initials: XJ
authors.lastname: Wang
authors.forename: J
authors.initials: J
authors.lastname: de Vrij
authors.forename: W J
authors.initials: WJ
authors.lastname: Liu
authors.forename: T T
authors.initials: TT
authors.lastname: Le
authors.forename: W A
authors.initials: WA
authors.lastname: Schroder
authors.forename: A A
authors.initials: AA
authors.lastname: Khromykh
authors.forename: A
authors.initials: A
authors.lastname: Suhrbier
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000627:therapeutic use; D003110:Colonic Neoplasms / Q000276:immunology / Q000628:therapy*; D005416:Flavivirus / Q000235:genetics; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis / Q000235:genetics*; D016898:Interferon-alpha / Q000096:biosynthesis; D016899:Interferon-beta / Q000096:biosynthesis; D008175:Lung Neoplasms / Q000517:prevention & control / Q000556:secondary; D008546:Melanoma, Experimental / Q000276:immunology / Q000628:therapy*; D051379:Mice; D009368:Neoplasm Transplantation; D012093:Replicon / Q000235:genetics*
chemical_list: D019496:Cancer Vaccines; D016898:Interferon-alpha; D016899:Interferon-beta; D016178:Granulocyte-Macrophage Colony-Stimulating Factor