Akbulut, HakanÇöleri, ArzuŞahin, GünceTang, YuchengDeisseroth, Albert2021-06-232021-06-2320180008-54721538-7445https://doi.org/10.1158/1538-7445.AM2018-5911https://hdl.handle.net/20.500.12491/9568Annual Meeting of the American-Association-for-Cancer-Research (AACR) -- APR 14-18, 2018 -- Chicago, ILBackground: Combination of cytotoxic treatments with immunotherapeutic agents seem more efficacious than using either strategy alone. Oncolytic viral vectors carrying immunostimulatory genes like GM-CSF have emerged as treatment options in various tumors. Previously, we have shown that combination of suicide gene therapy either with GM-CSF or vector-induced dendritic cells has significant anti-tumor efficacy. In the current study, we aimed to combine the cytotoxic effect of the suicide gene cytosine deaminase and the immunostimulatory effect of granulocyte macrophage colony stimulating factor in a single vector construct. Methods: We have constructed a bicistronic adenoviral vector carrying cytosine deaminase (CD) and granulocyte macrophage-colony stimulating factor (GM-CSF) genes combined with an IRES element and driven by CMV promoter (Ad-CMV-CDiresGMCSF). We tested the in vitro efficacy of the vector in various tumor cell lines and in a mouse model of colon cancer. Results: Our bicistronic vector Ad-CMV-CDiresGMCSF showed significant in-vitro cytotoxic effects on tumor cell lines similar to the vector carrying CD gene alone when 5-FC added. Likewise, the GM-CSF producing efficacy of the bicistronic vector was comparable to the vector carrying GM-CSF gene alone. In the syngeneic colon cancer model, the bicistronic vector carrying CD and GM-CSF genes yielded significant tumor shrinkage and overall survival when compared to the control suicide vector carrying CD gene alone. Accordingly, anti-tumor immune response parameters including CTL assay and immune cell infiltration of tumor tissue were significantly improved in the Ad-CMV-CDiresGMCSF vector treated group (p<0.01). Conclusions: The Ad-CMV-CDiresGMCSF vector construct suggests a potential for the treatment of established tumors by inducing significant tumor killing and tumor-specific immune response.eninfo:eu-repo/semantics/openAccessCytosine DeaminaseGM-CSF GenesBicistronic Adenoviral VectorColon CancerArticle10.1158/1538-7445.AM2018-59117813WOS:000468819505325Q1