Full metadata record
DC Field | Value | Language |
---|---|---|
dc.creator | Ballesteros-Briones, M.C. (María Cristina) | - |
dc.creator | Martisova, E. (Eva) | - |
dc.creator | Casales, E. (Erkuden) | - |
dc.creator | Silva-Pilipich, N.R. (Noelia Romina) | - |
dc.creator | Buñuales, M. (María) | - |
dc.creator | Galindo, J. (Javier) | - |
dc.creator | Mancheño, U. (Uxua) | - |
dc.creator | Gorraiz, M. (Marta) | - |
dc.creator | Lasarte, J.J. (Juan José) | - |
dc.creator | Kochan, G. (Grazyna) | - |
dc.creator | Escors, D. (David) | - |
dc.creator | Sanchez-Paulete, A.R. (Alfonso R.) | - |
dc.creator | Melero, I. (Ignacio) | - |
dc.creator | Prieto, J. (Jesús) | - |
dc.creator | Hernandez-Alcoceba, R. (Rubén) | - |
dc.creator | Hervas-Stubbs, S. (Sandra) | - |
dc.creator | Smerdou, C. (Cristian) | - |
dc.date.accessioned | 2021-09-14T10:54:41Z | - |
dc.date.available | 2021-09-14T10:54:41Z | - |
dc.date.issued | 2019 | - |
dc.identifier.citation | Ballesteros-Briones, M. C.; Martisová, E. (Eva); Casales-Zoco, E. (Erkuden); et al. "Short-term local expression of a PD-L1 blocking antibody from a self-replicating RNA vector induces potent antitumor responses". Molecular therapy. 27 (11), 2019, 1892 - 1905 | es |
dc.identifier.issn | 1525-0016 | - |
dc.identifier.uri | https://hdl.handle.net/10171/61993 | - |
dc.description.abstract | Immune checkpoint blockade has shown anti-cancer efficacy, but requires systemic administration of monoclonal antibodies (mAbs), often leading to adverse effects. To avoid toxicity, mAbs could be expressed locally in tumors. We developed adeno-associated virus (AAV) and Semliki Forest virus (SFV) vectors expressing anti-programmed death ligand 1 (aPDL1) mAb. When injected intratumorally in MC38 tumors, both viral vectors led to similar local mAb expression at 24 h, diminishing quickly in SFV-aPDL1-treated tumors. However, SFV-aPDL1 induced >40% complete regressions and was superior to AAV-aPDL1, as well as to aPDL1 mAb given systemically or locally. SFV-aPDL1 induced abscopal effects and was also efficacious against B16-ovalbumin (OVA). The higher SFV-aPDL1 antitumor activity could be related to local upregulation of interferon-stimulated genes because of SFV RNA replication. This was confirmed by combining local SFV-LacZ administration and systemic aPDL1 mAb, which provided higher antitumor effects than each separated agent. SFVaPDL1 promoted tumor-specific CD8 T cells infiltration in both tumor models. In MC38, SFV-aPDL1 upregulated co-stimulatory markers (CD137/OX40) in tumor CD8 T cells, and its combination with anti-CD137 mAb showed more pronounced antitumor effects than each single agent. These results indicate that local transient expression of immunomodulatory mAbs using non-propagative RNA vectors inducing type I interferon (IFN-I) responses represents a potent and s | - |
dc.description.sponsorship | This work was supported by the following grants: Instituto Salud Carlos III financed with Feder Funds PI17/01859 (to C.S.) and PI15/02027 (to S.H.S.), Gobierno de Navarra, Departamento de Salud 64/2019 (co-financed at 50% by the European Regional Development Fund through the FEDER Operational Program 2014-2020 of Navarra: “European Union. European Regional Development Fund. A way to make Europe”(to C.S.), “Fundacion Ramon Areces”(to S.H.-S.), and Spanish Ministry of Economy and Competitiveness SAF2015- 65157-R (to R.H.-A.). M.C.B.-B. received a Fundación Echébano fellowship. | - |
dc.language.iso | en | - |
dc.rights | info:eu-repo/semantics/openAccess | - |
dc.subject | Área de Medicina Clínica y Epidemiología | - |
dc.title | Short-term local expression of a PD-L1 blocking antibody from a self-replicating RNA vector induces potent antitumor responses | - |
dc.type | info:eu-repo/semantics/article | - |
dc.identifier.doi | 10.1016/j.ymthe.2019.09.016 | - |
dadun.citation.endingPage | 1905 | - |
dadun.citation.number | 11 | - |
dadun.citation.publicationName | Molecular therapy | - |
dadun.citation.startingPage | 1892 | - |
dadun.citation.volume | 27 | - |
Files in This Item:
Statistics and impact
Items in Dadun are protected by copyright, with all rights reserved, unless otherwise indicated.