AKT and JUN are differentially activated in mesenchymal stem cells after infection with human and canine oncolytic adenoviruses

Autor: Miguel Ángel Rodríguez-Milla, Ana Judith Perisé-Barrios, Alvaro Morales-Molina, Javier García-Castro, Teresa Cejalvo
Přispěvatelé: Instituto de Salud Carlos III, Comunidad de Madrid
Rok vydání: 2020
Předmět:
Zdroj: Cancer Gene Therapy. 28:64-73
ISSN: 1476-5500
0929-1903
Popis: Factor de impacto: 5,987 Q1 There is increasing evidence about the use of oncolytic adenoviruses (Ads) as promising immunotherapy agents. We have previously demonstrated the clinical efficiency of mesenchymal stem cells (MSCs) infected with oncolytic Ads as an antitumoral immunotherapy (called Celyvir) in human and canine patients, using ICOVIR-5 or ICOCAV17 as human and canine oncolytic Ads, respectively. Considering the better clinical outcomes of canine patients, in this study we searched for differences in cellular responses of human and canine MSCs to Ad infection that may help understand the mechanisms leading to higher antitumor immune response. We found that infection of human and canine MSCs with ICOVIR-5 or ICOCAV17 did not activate the NF-κB pathway or the interferon regulatory factors IRF3 and IRF7. However, we observed differences in the profile of cytokines secretion, as infection of canine MSCs with ICOCAV17 resulted in lower secretion of several cytokines. Moreover, we showed that infection of human MSCs with ICOVIR-5 increased the phosphorylation of a number of proteins, including AKT and c-JUN. Finally, we demonstrated that differences in regulation of AKT and c-JUN in human and canine MSCs by ICOVIR-5 or ICOCAV17 are intrinsic to each virus. Our findings suggest that ICOCAV17 induces a more limited host response in canine MSCs, which may be related to a better clinical outcome. This result opens the possibility to develop new human oncolytic Ads with these specific properties. In addition, this improvement could be imitated by selecting specific human MSC on the basis of a limited host response after Ad infection. This study was funded by Instituto de Salud Carlos III (PI14CIII/00005 and PI17CIII/00013 grants), Consejería de Educación, Juventud y Deporte of Comunidad de Madrid (P2017/BMD-3692 grant), Fundación Oncohematología Infantil, AFANION, and Asociación Pablo Ugarte, whose support we gratefully acknowledge. Sí
Databáze: OpenAIRE
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