title: Oncolytic adenovirus coding for granulocyte macrophage colony-stimulating factor induces antitumoral immunity in cancer patients.
abstract: Granulocyte macrophage colony-stimulating factor (GMCSF) can mediate antitumor effects by recruiting natural killer cells and by induction of tumor-specific cytotoxic T-cells through antigen-presenting cells. Oncolytic tumor cell-killing can produce a potent costimulatory danger signal and release of tumor epitopes for antigen-presenting cell sampling. Therefore, an oncolytic adenovirus coding for GMCSF was engineered and shown to induce tumor-specific immunity in an immunocompetent syngeneic hamster model. Subsequently, 20 patients with advanced solid tumors refractory to standard therapies were treated with Ad5-D24-GMCSF. Of the 16 radiologically evaluable patients, 2 had complete responses, 1 had a minor response, and 5 had disease stabilization. Responses were frequently seen in injected and noninjected tumors. Treatment was well tolerated and resulted in the induction of both tumor-specific and virus-specific immunity as measured by ELISPOT and pentamer analysis. This is the first time that oncolytic virus-mediated antitumor immunity has been shown in humans. Ad5-D24-GMCSF is promising for further clinical testing.
authors.affiliation: Cancer Gene Therapy Group, Transplantation Laboratory, Haartman Institute and Finnish Institute of Molecular Medicine, Department of Bacteriology and Immunology, Haartman Institute, Helsinki Medical Imaging Center, University of Helsinki, Helsinki, Finland.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Cerullo
authors.forename: Sari
authors.initials: S
authors.lastname: Pesonen
authors.forename: Iulia
authors.initials: I
authors.lastname: Diaconu
authors.forename: Sophie
authors.initials: S
authors.lastname: Escutenaire
authors.forename: Petteri T
authors.initials: PT
authors.lastname: Arstila
authors.forename: Matteo
authors.initials: M
authors.lastname: Ugolini
authors.forename: Petri
authors.initials: P
authors.lastname: Nokisalmi
authors.forename: Mari
authors.initials: M
authors.lastname: Raki
authors.forename: Leena
authors.initials: L
authors.lastname: Laasonen
authors.forename: Merja
authors.initials: M
authors.lastname: Särkioja
authors.forename: Maria
authors.initials: M
authors.lastname: Rajecki
authors.forename: Lotta
authors.initials: L
authors.lastname: Kangasniemi
authors.forename: Kilian
authors.initials: K
authors.lastname: Guse
authors.forename: Andreas
authors.initials: A
authors.lastname: Helminen
authors.forename: Laura
authors.initials: L
authors.lastname: Ahtiainen
authors.forename: Ari
authors.initials: A
authors.lastname: Ristimäki
authors.forename: Anne
authors.initials: A
authors.lastname: Räisänen-Sokolowski
authors.forename: Elina
authors.initials: E
authors.lastname: Haavisto
authors.forename: Minna
authors.initials: M
authors.lastname: Oksanen
authors.forename: Eerika
authors.initials: E
authors.lastname: Karli
authors.forename: Aila
authors.initials: A
authors.lastname: Karioja-Kallio
authors.forename: Sirkka-Liisa
authors.initials: SL
authors.lastname: Holm
authors.forename: Mauri
authors.initials: M
authors.lastname: Kouri
authors.forename: Timo
authors.initials: T
authors.lastname: Joensuu
authors.forename: Anna
authors.initials: A
authors.lastname: Kanerva
authors.forename: Akseli
authors.initials: A
authors.lastname: Hemminki
mesh_terms: D000256:Adenoviridae / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D000818:Animals; D006224:Cricetinae; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D016179:Granulocyte Colony-Stimulating Factor / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins / Q000276:immunology; D009369:Neoplasms / Q000235:genetics / Q000276:immunology / Q000628:therapy* / Q000821:virology; D050130:Oncolytic Virotherapy / Q000379:methods*; D000077022:Survivin; D013601:T-Lymphocytes / Q000276:immunology; D014162:Transfection
chemical_list: C107489:BIRC5 protein, human; D018984:Epitopes, T-Lymphocyte; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D000077022:Survivin; D016179:Granulocyte Colony-Stimulating Factor