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dc.creatorSilva-Pilipich, N.R. (Noelia Romina)-
dc.creatorBlanco, E. (E.)-
dc.creatorLozano, T. (Teresa)-
dc.creatorMartisova, E. (Eva)-
dc.creatorIgea, A. (Ana)-
dc.creatorHerrador-Cañete, G. (Guillermo)-
dc.creatorBallesteros-Briones, M.C. (María Cristina)-
dc.creatorGorraiz, M. (Marta)-
dc.creatorSarrión, P. (Patricia)-
dc.creatorGonzález-Sapienza, G. (Gualberto)-
dc.creatorLasarte, J.J. (Juan José)-
dc.creatorVanrell, L. (Lucía)-
dc.creatorSmerdou, C. (Cristian)-
dc.date.accessioned2023-09-21T07:36:57Z-
dc.date.available2023-09-21T07:36:57Z-
dc.date.issued2023-
dc.identifier.citationSilva-Pilipich, N.R. (Noelia Romina); Blanco, E. (E.); Lozano, T. (Teresa); et al. "Local delivery of optimized nanobodies targeting the PD-1/PD-L1 axis with a self-amplifying RNA viral vector induces potent antitumor responses". Cancer Letters. 561, 2023, 216139es_ES
dc.identifier.issn1872-7980-
dc.identifier.urihttps://hdl.handle.net/10171/67281-
dc.description.abstractDespite the success of immune checkpoint blockade for cancer therapy, many patients do not respond adequately. We aimed to improve this therapy by optimizing both the antibodies and their delivery route, using small monodomain antibodies (nanobodies) delivered locally with a self-amplifying RNA (saRNA) vector based on Semliki Forest virus (SFV). We generated nanobodies against PD-1 and PD-L1 able to inhibit both human and mouse interactions. Incorporation of a dimerization domain reduced PD-1/PD-L1 IC50 by 8- and 40-fold for antiPD-L1 and anti-PD-1 nanobodies, respectively. SFV viral particles expressing dimeric nanobodies showed a potent antitumor response in the MC38 model, resulting in >50% complete regressions, and showed better therapeutic efficacy compared to vectors expressing conventional antibodies. These effects were also observed in the B16 melanoma model. Although a short-term expression of nanobodies was observed due to the cytopathic nature of the saRNA vector, it was enough to generate a strong proinflammatory response in tumors, increasing infiltration of NK and CD8+ T cells. Delivery of the SFV vector expressing dimeric nanobodies by local plasmid electroporation, which could be more easily translated to the clinic, also showed a potent antitumor effect.es_ES
dc.description.sponsorshipThis work was supported by the following grants: Instituto Salud Carlos III financed with Feder Funds PI20/00415 (“A way to make Europe”), Gobierno de Navarra. Departamento de Salud (GN2022/21), and PLEC2021-008094 funded by the Spanish Ministry of Science and Innovation MCIN/AEI/10.13039/501100011033 and European Union Next Generation EU/PRTR. NSP received a “Ayudas predoctorales de investigaci´on biom´edica AC” fellowship.es_ES
dc.language.isoenges_ES
dc.publisherElsevieres_ES
dc.relationinfo:eu-repo/grantAgreement/ISCIII/Proyectos de investigación en salud/PI20/00415/[ES]/TERAPIA GENICA DEL CANCER COLORRECTAL UTILIZANDO UN VECTOR DE RNA AUTORREPLICATIVO PARA EXPRESAR INHIBIDORES DE ADHESION Y MIGRACION TUMORAL EN COMBINACION CON ANTICUERPOS INMUNOESTIMULADORESes_ES
dc.rightsinfo:eu-repo/semantics/openAccesses_ES
dc.subjectNanobodyes_ES
dc.subjectSFVes_ES
dc.subjectAlphaviruses_ES
dc.subjectPD-1/PD-L1es_ES
dc.subjectCancer immunotherapyes_ES
dc.titleLocal delivery of optimized nanobodies targeting the PD-1/PD-L1 axis with a self-amplifying RNA viral vector induces potent antitumor responseses_ES
dc.typeinfo:eu-repo/semantics/articlees_ES
dc.description.noteThis is an open access article under the CC BY-NC-ND licensees_ES
dc.identifier.doi10.1016/j.canlet.2023.216139-
dadun.citation.publicationNameCancer Letterses_ES
dadun.citation.startingPage216139es_ES
dadun.citation.volume561es_ES
dc.identifier.pmid37001752-

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