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AKT and JUN are differentially activated in mesenchymal stem cells after infection with human and canine oncolytic adenoviruses.
- Source :
-
Cancer gene therapy [Cancer Gene Ther] 2021 Feb; Vol. 28 (1-2), pp. 64-73. Date of Electronic Publication: 2020 May 27. - Publication Year :
- 2021
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Abstract
- 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.
- Subjects :
- Animals
Dogs
Humans
Mesenchymal Stem Cells immunology
Mesenchymal Stem Cells virology
Proto-Oncogene Proteins c-akt immunology
Proto-Oncogene Proteins c-jun immunology
Adenoviridae immunology
Mesenchymal Stem Cells metabolism
Oncolytic Virotherapy methods
Oncolytic Viruses immunology
Proto-Oncogene Proteins c-akt metabolism
Proto-Oncogene Proteins c-jun metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1476-5500
- Volume :
- 28
- Issue :
- 1-2
- Database :
- MEDLINE
- Journal :
- Cancer gene therapy
- Publication Type :
- Academic Journal
- Accession number :
- 32457488
- Full Text :
- https://doi.org/10.1038/s41417-020-0184-9