title: GMCSF-armed vaccinia virus induces an antitumor immune response.
abstract: Oncolytic Western Reserve strain vaccinia virus selective for epidermal growth factor receptor pathway mutations and tumor-associated hypermetabolism was armed with human granulocyte-macrophage colony-stimulating factor (GMCSF) and a tdTomato fluorophore. As the assessment of immunological responses to human transgenes is challenging in the most commonly used animal models, we used immunocompetent Syrian golden hamsters, known to be sensitive to human GMCSF and semipermissive to vaccinia virus. Efficacy was initially tested in vitro on various human and hamster cell lines and oncolytic potency of transgene-carrying viruses was similar to unarmed virus. The hGMCSF-encoding virus was able to completely eradicate subcutaneous pancreatic tumors in hamsters, and to fully protect the animals from subsequent rechallenge with the same tumor. Induction of specific antitumor immunity was also shown by ex vivo co-culture experiments with hamster splenocytes. In addition, histological examination revealed increased infiltration of neutrophils and macrophages in GMCSF-virus-treated tumors. These findings help clarify the mechanism of action of GMCSF-armed vaccinia viruses undergoing clinical trials.
authors.affiliation: Cancer Gene Therapy Group, Department of Pathology and Transplantation Laboratory, Haartman Institute, University of Helsinki, Helsinki, Finland.
authors.forename: Suvi
authors.initials: S
authors.lastname: Parviainen
authors.forename: Marko
authors.initials: M
authors.lastname: Ahonen
authors.forename: Iulia
authors.initials: I
authors.lastname: Diaconu
authors.forename: Anja
authors.initials: A
authors.lastname: Kipar
authors.forename: Mikko
authors.initials: M
authors.lastname: Siurala
authors.forename: Markus
authors.initials: M
authors.lastname: Vähä-Koskela
authors.forename: Anna
authors.initials: A
authors.lastname: Kanerva
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Cerullo
authors.forename: Akseli
authors.initials: A
authors.lastname: Hemminki
mesh_terms: D000818:Animals; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D018920:Coculture Techniques; D006224:Cricetinae; D004279:DNA, Viral / Q000235:genetics; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage*; D006801:Humans; D007124:Immunoenzyme Techniques; D008264:Macrophages; D008647:Mesocricetus; D050130:Oncolytic Virotherapy; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000276:immunology* / Q000628:therapy; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes; D014616:Vaccinia virus / Q000235:genetics* / Q000276:immunology; D014709:Vero Cells; D014779:Virus Replication / Q000276:immunology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D004279:DNA, Viral; D012333:RNA, Messenger; D016178:Granulocyte-Macrophage Colony-Stimulating Factor
keywords: GMCSF; immunotherapy; oncolytic vaccinia virus