Show simple item record

dc.contributorUniversitat Ramon Llull. IQS
dc.contributor.authorBorrós i Gómez, Salvador
dc.contributor.authorFornaguera Puigvert, Cristina
dc.contributor.authorBrugada Vilà, Pau
dc.contributor.authorFillat i Fonts, Cristina
dc.contributor.authorCascante, Anna
dc.contributor.authorLázaro, Miguel Ángel
dc.contributor.authorCastells-Sala, Cristina
dc.contributor.authorRovira-Rigau, Maria
dc.contributor.authorAlbertazzi, Lorenzo
dc.date.accessioned2022-03-01T19:35:27Z
dc.date.accessioned2023-07-13T05:45:11Z
dc.date.available2022-03-01T19:35:27Z
dc.date.available2023-07-13T05:45:11Z
dc.date.issued2020-02
dc.identifier.urihttp://hdl.handle.net/20.500.14342/1076
dc.description.abstractOncolytic adenoviruses are used as agents for the treatment of cancer. However, their potential is limited due to the high seroprevalence of anti-adenovirus neutralizing antibodies (nAbs) within the population and the rapid liver sequestration when systemically administered. To overcome these challenges, we explored using nanoparticle formulation to boost the efficacy of systemic oncolytic adenovirus administration. Methods: Adenovirus were conjugated with PEGylated oligopeptide-modified poly(β-amino ester)s (OM-pBAEs). The resulting coated viral formulation was characterized in terms of surface charge, size, aggregation state and morphology and tested for anti-adenovirus nAbs evasion and activity in cancer cells. In vivo pharmacokinetics, biodistribution, tumor targeting, and immunogenicity studies were performed. The antitumor efficacy of the oncolytic adenovirus AdNuPARmE1A coated with OM-pBAEs (SAG101) in the presence of nAbs was evaluated in pancreatic ductal adenocarcinoma (PDAC) mouse models. Toxicity of the coated formulation was analyzed in vivo in immunocompetent mice. Results: OM-pBAEs conjugated to adenovirus and generated discrete nanoparticles with a neutral charge and an optimal size. The polymeric coating with the reporter AdGFPLuc (CPEG) showed enhanced transduction and evasion of antibody neutralization in vitro. Moreover, systemic intravenous administration of the formulation showed improved blood circulation and reduced liver sequestration, substantially avoiding activation of nAb production. OM-pBAEs coating of the oncolytic adenovirus AdNuPARmE1A (SAG101) improved its oncolytic activity in vitro and enhanced antitumor efficacy in PDAC mouse models. The coated formulation protected virions from neutralization by nAbs, as antitumor efficacy was preserved in their presence but was completely lost in mice that received the non-formulated AdNuPARmE1A. Finally, coated-AdNuPARmE1A showed reduced toxicity when high doses of the formulation were administered. Conclusions: The developed technology represents a promising improvement for future clinical cancer therapy using oncolytic adenoviruses.eng
dc.format.extent15 p.cat
dc.language.isoengcat
dc.publisherIvyspring International Publishercat
dc.relation.ispartofTheranostics. Vol.10, n.6 (2020), p. 2744-2758cat
dc.rightsAttribution 4.0 International
dc.rights© L'autor/a
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceRECERCAT (Dipòsit de la Recerca de Catalunya)
dc.subject.otherPàncrees--Càncercat
dc.subject.otherAdenoviruscat
dc.subject.otherPolièsterscat
dc.subject.otherOncolytic adenoviruscat
dc.subject.otherPolymer-coated viral vectorscat
dc.subject.otherPoly(β-amino ester)scat
dc.subject.otherPancreatic cancercat
dc.subject.otherSystemic deliverycat
dc.titleOligopeptide-modified poly(beta-amino ester)s-coated AdNuPARmE1A: boosting the efficacy of intravenously administered therapeutic adenovirusescat
dc.typeinfo:eu-repo/semantics/articlecat
dc.typeinfo:eu-repo/semantics/publishedVersioncat
dc.rights.accessLevelinfo:eu-repo/semantics/openAccess
dc.embargo.termscapcat
dc.subject.udc616
dc.identifier.doihttps://doi.org/10.7150/thno.40902cat
dc.relation.projectIDinfo:eu-repo/grantAgreement/MINECO i FEDER/PN I+D/BIO2017-89754-C2-2Rcat
dc.relation.projectIDinfo:eu-repo/grantAgreement/MINECO i FEDER/PN I+D/RTC-2015-3751-1cat
dc.relation.projectIDinfo:eu-repo/grantAgreement/MINECO i FEDER/PN I+D/RTC-2015-3751-1cat
dc.relation.projectIDinfo:eu-repo/grantAgreement/MINECO i FEDER/PN I+D/SAF2015-64927-C2-1-Rcat
dc.relation.projectIDinfo:eu-repo/grantAgreement/MINECO i FEDER/PN I+D/SAF2015-64927-C2-2-Rcat
dc.relation.projectIDinfo:eu-repo/grantAgreement/MINECO/PN I+D/Torres Quevedo 2015cat
dc.relation.projectIDinfo:eu-repo/grantAgreement/SUR del DEC/SGR/2017 SGR 861cat
dc.relation.projectIDinfo:eu-repo/grantAgreement/SUR del DEC/SGR/2017 SGR 1559cat


Files in this item

 

This item appears in the following Collection(s)

Show simple item record

Attribution 4.0 International
Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by/4.0/
Share on TwitterShare on LinkedinShare on FacebookShare on TelegramShare on WhatsappPrint