Mesenchymal stem cell carriers enhance antitumor efficacy of oncolytic adenoviruses in an immunocompetent mouse model.

Abstract

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.

• Authors: Esther Rincón, Teresa Cejalvo, Deepak Kanojia, Arantzazu Alfranca, Miguel Ángel Rodríguez-Milla, Raul Andrés Gil Hoyos, Yu Han, Lingjiao Zhang, Ramón Alemany, Maciej S Lesniak, Javier García-Castro
• Journal: Oncotarget (Oncotarget) Vol. 8 Issue 28 Pg. 45415-45431 (Jul 11 2017) ISSN: 1949-2553 [Electronic] United States
• PMID: 28525366 (Publication Type: Journal Article)

Chemical References

• Cytokines
• Inflammation Mediators

Topics

• Adenoviridae (genetics)
• Animals
• Cell Line, Tumor
• Cell Movement
• Cell Survival (genetics)
• Cytokines (metabolism)
• Disease Models, Animal
• Gene Expression
• Genes, Reporter
• Genetic Therapy
• Genetic Vectors (genetics)
• Humans
• Immunotherapy
• Inflammation Mediators (metabolism)
• Lymphocytes, Tumor-Infiltrating (immunology, metabolism)
• Mesenchymal Stem Cell Transplantation
• Mesenchymal Stem Cells (metabolism)
• Mice
• Oncolytic Virotherapy
• Oncolytic Viruses (genetics)
• Transduction, Genetic
• Xenograft Model Antitumor Assays