Please use this identifier to cite or link to this item:http://hdl.handle.net/20.500.12105/9612
Mesenchymal stem cell carriers enhance antitumor efficacy of oncolytic adenoviruses in an immunocompetent mouse model
Rincon, Esther ISCIII | Cejalvo, Teresa ISCIII | Kanojia, Deepak | Alfranca, Arantzazu ISCIII | Rodriguez-Milla, Miguel A ISCIII | Gil Hoyos, Raul Andrés | Han, Yu | Zhang, Lingjiao | Alemany, Ramón | Lesniak, Maciej S | Garcia-Castro, Javier ISCIII
Oncotarget. 2017 Jul 11;8(28):45415-45431.
Oncolytic virotherapy represents a promising alternative for cancer treatment; however, viral delivery to the tumor represents a major challenge. Mesenchymal stem cells (MSCs) chemotax to tumors, and can serve as a viral delivery tool. Previously, we demonstrated antitumor therapeutic efficacy for mesenchymal stem cells (MSCs) infected with the oncolytic human adenovirus ICOVIR5 (Celyvir) for treatment of neuroblastoma patients. Given the lack of suitable immunocompetent preclinical models, the mechanism underlying Celyvir antitumor activity remains unknown. In this study, we used the syngeneic murine CMT64 cell line as a human adenovirus-semi-permissive tumor model and demonstrate the homing capacity of mouse Celyvir (mCelyvir) to CMT64 tumors. We found that the combined treatment of mCelyvir and intratumoral injections (i.t.) of ICOVIR5 was more effective than treatment with i.t. ICOVIR5 alone. Interestingly, the superior therapeutic effect of the combined therapy was associated with a higher tumor infiltration of CD8+ and CD4+ T cells. Our findings suggest that the use of MSCs as carriers of oncolytic adenovirus can improve the clinical efficacy of anti-cancer virotherapy, not only by driving the adenovirus to tumors, but also through their potential to recruit T cells.
Animals | Cell Line, Tumor | Cell Movement | Cell Survival | Cytokines | Disease Models, Animal | Gene Expression | Genes, Reporter | Genetic Therapy | Humans | Immunotherapy | Inflammation Mediators | Lymphocytes, Tumor-Infiltrating | Mesenchymal Stem Cells | Mice | Transduction, Genetic | Xenograft Model Antitumor Assays | Adenoviridae | Genetic Vectors | Mesenchymal Stem Cell Transplantation | Oncolytic Virotherapy | Oncolytic Viruses
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