title: Antiviral and antitumor T-cell immunity in patients treated with GM-CSF-coding oncolytic adenovirus.
abstract: OBJECTIVE
  Multiple injections of oncolytic adenovirus could enhance immunologic response. In the first part of this article, the focus was on immunologic aspects. Sixty patients previously naïve to oncolytic virus and who had white blood cells available were treated. Thirty-nine of 60 were assessed after a single virus administration, whereas 21 of 60 received a "serial treatment" consisting of three injections within 10 weeks. In the second part, we focused on 115 patients treated with a granulocyte macrophage colony-stimulating factor (GM-CSF)-coding capsid chimeric adenovirus, CGTG-102.
  
  
  RESULTS
  Following serial treatment, both increase and decrease in antitumor T cells in blood were seen more frequently, findings which are compatible with induction of T-cell immunity and trafficking of T cells to tumors, respectively. Safety was good in both groups. In 115 patients treated with CGTG-102 (Ad5/3-D24-GMCSF), median overall survival was 111 days following single and 277 days after serial treatment in nonrandomized comparison. Switching the virus capsid for avoiding neutralizing antibodies in a serial treatment featuring three different viruses did not impact safety or efficacy. A correlation between antiviral and antitumor T cells was seen (P = 0.001), suggesting that viral oncolysis can result in epitope spreading and breaking of tumor-associated immunologic tolerance. Alternatively, some patients may be more susceptible to induction of T-cell immunity and/or trafficking.
  
  
  CONCLUSIONS
  These results provide the first human data linking antiviral immunity with antitumor immunity, implying that oncolytic viruses could have an important role in cancer immunotherapy.
authors.affiliation: Cancer Gene Therapy Group, Department of Pathology and Transplantation Laboratory, Haartman Institute, University of Helsinki, Helsinki, Finland.
authors.forename: Anna
authors.initials: A
authors.lastname: Kanerva
authors.forename: Petri
authors.initials: P
authors.lastname: Nokisalmi
authors.forename: Iulia
authors.initials: I
authors.lastname: Diaconu
authors.forename: Anniina
authors.initials: A
authors.lastname: Koski
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Cerullo
authors.forename: Ilkka
authors.initials: I
authors.lastname: Liikanen
authors.forename: Siri
authors.initials: S
authors.lastname: Tähtinen
authors.forename: Minna
authors.initials: M
authors.lastname: Oksanen
authors.forename: Raita
authors.initials: R
authors.lastname: Heiskanen
authors.forename: Saila
authors.initials: S
authors.lastname: Pesonen
authors.forename: Timo
authors.initials: T
authors.lastname: Joensuu
authors.forename: Tuomo
authors.initials: T
authors.lastname: Alanko
authors.forename: Kaarina
authors.initials: K
authors.lastname: Partanen
authors.forename: Leena
authors.initials: L
authors.lastname: Laasonen
authors.forename: Kalevi
authors.initials: K
authors.lastname: Kairemo
authors.forename: Sari
authors.initials: S
authors.lastname: Pesonen
authors.forename: Lotta
authors.initials: L
authors.lastname: Kangasniemi
authors.forename: Akseli
authors.initials: A
authors.lastname: Hemminki
mesh_terms: D000256:Adenoviridae / Q000235:genetics / Q000276:immunology; D000293:Adolescent; D000328:Adult; D000368:Aged; D036022:Capsid Proteins / Q000235:genetics / Q000276:immunology; D002648:Child; D017635:Clonal Anergy / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000145:classification / Q000276:immunology* / Q000628:therapy*; D050130:Oncolytic Virotherapy / Q000379:methods*; D050504:Oncolytic Viruses / Q000235:genetics / Q000276:immunology; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D013997:Time Factors; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism; D055815:Young Adult
chemical_list: D036022:Capsid Proteins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor