dc.creator | Viale, Diego Luis | |
dc.creator | Cafferata, Eduardo Gustavo Alfredo | |
dc.creator | Gould, David | |
dc.creator | Rotondaro, Cecilia | |
dc.creator | Chernajovsky, Yuti | |
dc.creator | Curiel, David T. | |
dc.creator | Podhajcer, Osvaldo Luis | |
dc.creator | Lopez, Maria Veronica | |
dc.date.accessioned | 2017-07-06T13:49:15Z | |
dc.date.available | 2017-07-06T13:49:15Z | |
dc.date.created | 2017-07-06T13:49:15Z | |
dc.date.issued | 2013-11 | |
dc.identifier | Viale, Diego Luis; Cafferata, Eduardo Gustavo Alfredo; Gould, David; Rotondaro, Cecilia; Chernajovsky, Yuti; et al.; Therapeutic improvement of a stroma-targeted CRAd by incorporating motives responsive to melanoma microenvironment; Williams & Wilkins; Journal Of Investigative Dermatology; 133; 11; 11-2013; 2576-2584 | |
dc.identifier | 0022-202X | |
dc.identifier | http://hdl.handle.net/11336/19713 | |
dc.identifier | 1523-1747 | |
dc.identifier | CONICET Digital | |
dc.identifier | CONICET | |
dc.description.abstract | We have previously designed a conditionally replicative oncolytic adenovirus (CRAd) named Ad-F512 that can target both the stromal and the malignant melanoma cell compartments. The replication capacity of this CRAd is driven by a 0.5-Kb SPARC promoter fragment (named F512). To improve CRAd's efficacy, we cloned into F512 motives responsive to hypoxia (hypoxia-responsive element (HRE)) and inflammation (nuclear factor kappa B) to obtain a chimeric promoter named κBF512HRE. Using luciferase as a reporter gene, we observed 10-15-fold increased activity under hypoxia and 10-80-fold induction upon tumor necrosis factor-α addition. We next constructed a CRAd (Ad-κBF512HRE) where E1A activity was under κBF512HRE regulation. Treatment of nude mice harboring established tumors made of a mix of SB2 melanoma cells and WI-38 fibroblasts with Ad-κBF512HRE led to the complete elimination of tumors in 100% of mice (8/8). Moreover, Ad-5/3-κBF512HRE, a viral variant pseudotyped with a chimeric 5/3 fiber, exerted a strong lytic effect on CAR-negative melanoma cells and was highly effective in vivo on established tumors made of melanoma cells and WI-38 fibroblasts, leading to the complete elimination of 4/5 tumors. These results indicate that this improved stroma-targeted oncolytic adenovirus can override the resistance of melanoma tumors and might become of significant importance for melanoma therapeutics. | |
dc.language | eng | |
dc.publisher | Williams & Wilkins | |
dc.relation | info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0022202X15360279 | |
dc.relation | info:eu-repo/semantics/altIdentifier/doi/https://doi.org/10.1038/jid.2013.191 | |
dc.relation | info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4159097/ | |
dc.rights | https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ | |
dc.rights | info:eu-repo/semantics/openAccess | |
dc.subject | Viroterapia | |
dc.subject | Cancer | |
dc.subject | Melanoma | |
dc.subject | Estroma | |
dc.title | Therapeutic improvement of a stroma-targeted CRAd by incorporating motives responsive to melanoma microenvironment | |
dc.type | info:eu-repo/semantics/article | |
dc.type | info:ar-repo/semantics/artículo | |
dc.type | info:eu-repo/semantics/publishedVersion | |