A bicistronic adenoviral vector carrying cytosine deaminase and granulocyte-macrophage colony-stimulating factor increases the therapeutic efficacy of cancer gene therapy

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dc.authorid0000-0001-6784-6850en_US
dc.authorid0000-0003-0060-259X
dc.authorid0000-0002-7289-62510
dc.contributor.authorAkbulut, Hakan
dc.contributor.authorÇöleri, Arzu
dc.contributor.authorŞahin, Günce
dc.contributor.authorTang, Yucheng
dc.contributor.authorİçli, Fikri
dc.date.accessioned2021-06-23T19:51:48Z
dc.date.available2021-06-23T19:51:48Z
dc.date.issued2019
dc.departmentBAİBÜ, Fen Edebiyat Fakültesi, Biyoloji Bölümüen_US
dc.description.abstractThe combination of cytotoxic treatment modalities, including oncolytic viral gene therapies and immunotherapy, usually yields a synergistic effect. In the current study, a bicistronic adenoviral vector, Ad-CD-GMCSF, carrying the cytosine deaminase (CD) and granulocyte-macrophage colony-stimulating factor (GM-CSF) transcription units driven by a cytomegalovirus promoter was constructed, and the in vitro efficacy of the vector was tested in tumor cell lines and a syngeneic mouse model of colon cancer. The tumor cells infected with Ad-CD-GMCSF vector were found to produce a substantial amount of GM-CSF in tumor cell lines. Accordingly, the vector carrying CD and GM-CSF transcription units together induced a potent antitumor immunity with a significantly increased number of tumor-specific T cells and tumor-specific T-cell cytotoxicity (p < 0.001). The tumor growth rate of Ad-CD-GMCSF-treated mice was significantly lower when compared to the control and an adenoviral vector carrying only the CD transcription unit (Ad-CD; p < 0.05). Likewise, the median overall survival of the Ad-CD-GMCSF vector group was significantly higher than that of the control and Ad-CD groups (34.0 +/- 12.8 vs. 14.0 +/- 0.5 and 23.0 +/- 2.8 days, respectively; p < 0.001). In conclusion, along with its cytotoxic effect, the high immunostimulatory effect of the bicistronic Ad-CD-GMCSF vector has excellent potential in the treatment of cancers.en_US
dc.identifier.doi10.1089/hum.2018.245
dc.identifier.endpage1007en_US
dc.identifier.issn1043-0342
dc.identifier.issn1557-7422
dc.identifier.issue8en_US
dc.identifier.pmid30892086en_US
dc.identifier.scopus2-s2.0-85070826426en_US
dc.identifier.scopusqualityQ2en_US
dc.identifier.startpage999en_US
dc.identifier.urihttps://doi.org/10.1089/hum.2018.245
dc.identifier.urihttps://hdl.handle.net/20.500.12491/10049
dc.identifier.volume30en_US
dc.identifier.wosWOS:000465471600001en_US
dc.identifier.wosqualityQ1en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.institutionauthorŞahin, Günce
dc.language.isoenen_US
dc.publisherMary Ann Liebert, Incen_US
dc.relation.ispartofHuman Gene Therapyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectGene Therapyen_US
dc.subjectGM-CSFen_US
dc.subjectCytosine Deaminaseen_US
dc.subjectAdenoviral Vectoren_US
dc.subject5-fluorouracilen_US
dc.titleA bicistronic adenoviral vector carrying cytosine deaminase and granulocyte-macrophage colony-stimulating factor increases the therapeutic efficacy of cancer gene therapyen_US
dc.typeArticleen_US

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