Full metadata record
DC Field | Value | Language |
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dc.creator | Quetglas, J.I. (José Ignacio) | - |
dc.creator | Dubrot, J. (Juan) | - |
dc.creator | Bezunartea, J. (Jaione) | - |
dc.creator | Fernandez-Sanmamed, M. (Miguel) | - |
dc.creator | Hervas-Stubbs, S. (Sandra) | - |
dc.creator | Smerdou, C. (Cristian) | - |
dc.creator | Melero, I. (Ignacio) | - |
dc.date.accessioned | 2014-08-30T17:35:11Z | - |
dc.date.available | 2014-08-30T17:35:11Z | - |
dc.date.issued | 2012-09-04 | - |
dc.identifier.citation | Quetglas JI, Dubrot J, Bezunartea J, Sanmamed MF, Hervas-Stubbs S, Smerdou C, et al. Immunotherapeutic synergy between anti-CD137 mAb and intratumoral administration of a cytopathic Semliki Forest virus encoding IL-12. Mol Ther. 2012 Sep;20(9):1664-1675 | es_ES |
dc.identifier.issn | 1525-0016 | - |
dc.identifier.uri | https://hdl.handle.net/10171/36420 | - |
dc.description.abstract | Intratumoral injection of Semliki Forest virus encoding interleukin-12 (SFV-IL-12) combines acute expression of IL-12 and stressful apoptosis of infected malignant cells. Agonist antibodies directed to costimulatory receptor CD137 (4-1BB) strongly amplify pre-existing cellular immune responses toward weak tumor antigens. In this study, we provide evidence for powerful synergistic effects of a combined strategy consisting of intratumoral injection of SFV-IL-12 and systemic delivery of agonist anti-CD137 monoclonal antibodies (mAbs), which was substantiated against poorly immunogenic B16 melanomas (B16-OVA and B16.F10) and TC-1 lung carcinomas. Effector CD8(β)(+) T cells were sufficient to mediate complete tumor eradications. Accordingly, there was an intensely synergistic in vivo enhancement of cytotoxic T lymphocytes (CTL)-mediated immunity against the tumor antigens OVA and tyrosine-related protein-2 (TRP-2). This train of phenomena led to long-lasting tumor-specific immunity against rechallenge, attained transient control of the progression of concomitant tumor lesions that were not directly treated with SFV-IL-12 and caused autoimmune vitiligo. Importantly, we found that SFV-IL-12 intratumoral injection induces bright expression of CD137 on most tumor-infiltrating CD8(+) T lymphocytes, thereby providing more abundant targets for the action of the agonist antibody. This efficacious combinatorial immunotherapy strategy offers feasibility for clinical translation since anti-CD137 mAbs are already undergoing clinical trials and development of clinical-grade SFV-IL-12 vectors is in progress. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Nature Publishing Group | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.subject | Antigens, CD137 | es_ES |
dc.subject | Interleukin-12 | es_ES |
dc.subject | Carcinoma | es_ES |
dc.subject | Semliki forest virus | es_ES |
dc.title | Immunotherapeutic synergy between anti-CD137 mAb and intratumoral administration of a cytopathic Semliki Forest virus encoding IL-12 | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.identifier.doi | http://dx.doi.org/10.1038/mt.2012.56 | es_ES |
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