Immunological data from cancer patients treated with Ad5/3-E2F-Delta 24-GMCSF suggests utility for tumor immunotherapy

Show simple item record Hemminki, Otto Parviainen, Suvi Juhila, Juuso Turkki, Riku Linder, Nina Lundin, Johan Kankainen, Matti Ristimaki, Ari Koski, Anniina Liikanen, Ilkka Oksanen, Minna Nettelbeck, Dirk M. Kairemo, Kalevi Partanen, Kaarina Joensuu, Timo Kanerva, Anna Hemminki, Akseli 2017-10-11T08:55:02Z 2017-10-11T08:55:02Z 2015-02-28
dc.identifier.citation Hemminki , O , Parviainen , S , Juhila , J , Turkki , R , Linder , N , Lundin , J , Kankainen , M , Ristimaki , A , Koski , A , Liikanen , I , Oksanen , M , Nettelbeck , D M , Kairemo , K , Partanen , K , Joensuu , T , Kanerva , A & Hemminki , A 2015 , ' Immunological data from cancer patients treated with Ad5/3-E2F-Delta 24-GMCSF suggests utility for tumor immunotherapy ' , Oncotarget , vol. 6 , no. 6 , pp. 4467-4481 .
dc.identifier.other PURE: 48854741
dc.identifier.other PURE UUID: 36ad5195-2efa-410c-8a30-fd0fb3fc9c71
dc.identifier.other WOS: 000352696200079
dc.identifier.other Scopus: 84924280819
dc.identifier.other ORCID: /0000-0002-8690-6983/work/39665637
dc.identifier.other ORCID: /0000-0003-3930-0513/work/56158098
dc.identifier.other ORCID: /0000-0003-3601-2786/work/61594081
dc.description.abstract Oncolytic viruses that selectively replicate in tumor cells can be used for treatment of cancer. Accumulating data suggests that virus induced oncolysis can enhance anti-tumor immunity and break immune tolerance. To capitalize on the immunogenic nature of oncolysis, we generated a quadruple modified oncolytic adenovirus expressing granulocyte-macrophage colony-stimulating factor (GMCSF). Ad5/3-E2F-Delta 24-GMCSF (CGTG-602) was engineered to contain a tumor specific E2F1 promoter driving an E1 gene deleted at the retinoblastoma protein binding site ("Delta 24"). The fiber features a knob from serotype 3 for enhanced gene delivery to tumor cells. The virus was tested preclinically in vitro and in vivo and then 13 patients with solid tumors refractory to standard therapies were treated. Treatments were well tolerated and frequent tumor-and adenovirus-specific T-cell immune responses were seen. Overall, with regard to tumor marker or radiological responses, signs of antitumor efficacy were seen in 9/12 evaluable patients (75%). The radiological disease control rate with positron emission tomography was 83% while the response rate (including minor responses) was 50%. Tumor biopsies indicated accumulation of immunological cells, especially T-cells, to tumors after treatment. RNA expression analyses of tumors indicated immunological activation and metabolic changes secondary to virus replication. en
dc.format.extent 15
dc.language.iso eng
dc.relation.ispartof Oncotarget
dc.rights cc_by
dc.rights.uri info:eu-repo/semantics/openAccess
dc.subject Oncolytic
dc.subject immunotherapy
dc.subject cancer
dc.subject ATAP
dc.subject T-CELL
dc.subject GM-CSF
dc.subject RETINOIC ACID
dc.subject SOLID TUMORS
dc.subject 3122 Cancers
dc.title Immunological data from cancer patients treated with Ad5/3-E2F-Delta 24-GMCSF suggests utility for tumor immunotherapy en
dc.type Article
dc.contributor.organization Transplantation Laboratory
dc.contributor.organization Medicum
dc.contributor.organization Institute for Molecular Medicine Finland
dc.contributor.organization Department of Pathology
dc.contributor.organization Research Programs Unit
dc.contributor.organization Genome-Scale Biology (GSB) Research Program
dc.contributor.organization Clinicum
dc.contributor.organization Gastrointestinal tumorigenesis
dc.contributor.organization University of Helsinki
dc.contributor.organization Department of Obstetrics and Gynecology
dc.description.reviewstatus Peer reviewed
dc.relation.issn 1949-2553
dc.rights.accesslevel openAccess
dc.type.version publishedVersion

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