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

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Pysyväisosoite

http://hdl.handle.net/10138/225316

Lähdeviite

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 . https://doi.org/10.18632/oncotarget.2901

Julkaisun nimi: Immunological data from cancer patients treated with Ad5/3-E2F-Delta 24-GMCSF suggests utility for tumor immunotherapy
Tekijä: 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
Tekijän organisaatio: Transplantation Laboratory
Medicum
Institute for Molecular Medicine Finland
Department of Pathology
Research Programs Unit
Genome-Scale Biology (GSB) Research Program
Clinicum
Gastrointestinal tumorigenesis
University of Helsinki
Department of Obstetrics and Gynecology
Päiväys: 2015-02-28
Kieli: eng
Sivumäärä: 15
Kuuluu julkaisusarjaan: Oncotarget
ISSN: 1949-2553
DOI-tunniste: https://doi.org/10.18632/oncotarget.2901
URI: http://hdl.handle.net/10138/225316
Tiivistelmä: 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.
Avainsanat: Oncolytic
immunotherapy
cancer
ATAP
CHEMOTHERAPY-REFRACTORY CANCER
ANTITUMOR IMMUNE-RESPONSES
COLONY-STIMULATING FACTOR
ONCOLYTIC ADENOVIRUS
OVARIAN-CANCER
T-CELL
GM-CSF
THERAPEUTIC-EFFICACY
RETINOIC ACID
SOLID TUMORS
3122 Cancers
Vertaisarvioitu: Kyllä
Tekijänoikeustiedot: cc_by
Pääsyrajoitteet: openAccess
Rinnakkaistallennettu versio: publishedVersion


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