Radiotherapy synergizes with an inducible AAV-based immunotherapy platform to program local and systemic antitumor immunity
Marco, Sonia ; Fernández, Myriam ; Honorato, Beatriz ; Juanarena, Nerea ; Sainz, Cristina ; Andueza, Ainhoa ; Gould, David J. ; Anderson, Seth ; de Andrea, Carlos ; Domínguez, Paulo Pérez ; Wong, Paolo ; Vásquez, Carlos ; Narinda, Irene ; Unzu, Carmen ; Isola, Sergio ; Tavira, Beatriz ; Ariz, Mikel ; Camps, Gracián ; Sanmamed, Miguel F. ; Pardo, Julián (Universidad de Zaragoza) ; Labiano, Sara ; Alonso, Marta M. ; Marco-Sanz, Javier ; Guruceaga, Elizabeth ; Collantes, María ; Simón, Jon Ander ; Peñuelas, Iván ; Fernández-Irigoyen, Joaquín ; Santamaría, Enrique ; Prieto, Jesús ; Dubrot, Juan
Resumen: Radiotherapy (RT) can prime the immune system against cancer but often fails to generate effective antitumor responses due to concomitant induction of immunosuppressive factors. To overcome this limitation, we built upon the observation that RT enhances adeno-associated vectors (AAVs) tumor transduction through the epigenetic modification of vector episomes. We designed an AAV-based platform to deliver immunostimulatory cytokines through an interferon (IFN)-inducible promoter that allows for spatial control of transgene expression into irradiated tumors. As opposed to a constitutive system, local delivery of a vector encoding for inducible IL-12 (AAV-iIL12) achieves an efficient production of the cytokine without significant toxicity. Combination of RT and AAV-iIL12 generates a highly immunostimulatory tumor microenvironment (TME) leading to robust local and systemic antitumor responses in an IFNγ- and FAS-dependent manner, able to overcome common immune-evasion mechanisms. Our work shows that radiation coupled with AAV-based immune-gene delivery is an efficient and safe approach to treat cancer.
Idioma: Inglés
DOI: 10.1016/j.ccell.2026.02.013
Año: 2026
Publicado en: CANCER CELL 44 (2026), 17 pp.
ISSN: 1535-6108
Financiación: info:eu-repo/grantAgreement/ES/DGA/B29-20R
Financiación: info:eu-repo/grantAgreement/ES/ISCIII/CB21-13-00087
Financiación: info:eu-repo/grantAgreement/ES/MCIU-AEI/PID2020-113963RB-I00 Desasignar
Financiación: info:eu-repo/grantAgreement/ES/MCIU/PID2024-160227OB-I00
Tipo y forma: Article (Published version)
Área (Departamento): Área Inmunología (Dpto. Microb.Ped.Radio.Sal.Pú.)
You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use. You may not use the material for commercial purposes.
Exportado de SIDERAL (2026-05-05-13:36:17)
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Idioma: Inglés
DOI: 10.1016/j.ccell.2026.02.013
Año: 2026
Publicado en: CANCER CELL 44 (2026), 17 pp.
ISSN: 1535-6108
Financiación: info:eu-repo/grantAgreement/ES/DGA/B29-20R
Financiación: info:eu-repo/grantAgreement/ES/ISCIII/CB21-13-00087
Financiación: info:eu-repo/grantAgreement/ES/MCIU-AEI/PID2020-113963RB-I00 Desasignar
Financiación: info:eu-repo/grantAgreement/ES/MCIU/PID2024-160227OB-I00
Tipo y forma: Article (Published version)
Área (Departamento): Área Inmunología (Dpto. Microb.Ped.Radio.Sal.Pú.)
You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use. You may not use the material for commercial purposes. Exportado de SIDERAL (2026-05-05-13:36:17)
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Record created 2026-05-05, last modified 2026-05-05