title: Expressing human interleukin-15 from oncolytic vesicular stomatitis virus improves survival in a murine metastatic colon adenocarcinoma model through the enhancement of anti-tumor immunity.
abstract: In this study, we sought to enhance the potency of an oncolytic virus, vesicular stomatitis virus (VSV), by inserting a transgene encoding a highly secreted version of human interleukin-15 (IL-15). IL-15 has shown promise as an immunotherapeutic cytokine, as it is able to enhance both natural killer (NK) and T-cell responses, but it has not yet been tested as a therapeutic transgene in the context of viral oncolysis. The transgene was modified to ensure enhanced secretion of IL-15 from infected cells, leading to strong localized expression from infected CT-26 tumors in vivo. This localized expression in the tumor microenvironment led to a clear enhancement to anti-tumoral T-cell responses and enhanced survival, while additional IL-15 administration systemically failed to further enhance the therapy. Overall, the transient localized expression of IL-15 in the tumour by an oncolytic virus was able to induce stronger anti-tumoral immunity in a murine model of colon carcinoma.
authors.affiliation: Department of Pathology and Molecular Medicine, Centre for Gene Therapeutics, McMaster Immunology Research Centre, McMaster University, Hamilton, Ontario, Canada.
authors.forename: K B
authors.initials: KB
authors.lastname: Stephenson
authors.forename: N G
authors.initials: NG
authors.lastname: Barra
authors.forename: E
authors.initials: E
authors.lastname: Davies
authors.forename: A A
authors.initials: AA
authors.lastname: Ashkar
authors.forename: B D
authors.initials: BD
authors.lastname: Lichty
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D000818:Animals; D002460:Cell Line; D002522:Chlorocebus aethiops; D003110:Colonic Neoplasms / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D023061:Gene Order; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics*; D006801:Humans; D019409:Interleukin-15 / Q000235:genetics*; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis; D050130:Oncolytic Virotherapy; D050504:Oncolytic Viruses / Q000235:genetics*; D014161:Transduction, Genetic; D014721:Vesicular stomatitis Indiana virus / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays
chemical_list: D019409:Interleukin-15