Infectious bursal disease virus (IBDV) as a novel oncolytic virotherapy in glioblastoma

Background Glioblastoma (GBM) is the most aggressive form of cancer of the central nervous system. Despite advances in immunotherapies and standard-of-care treatments for GBMs, clinical outcomes remain limited— owing to the immunosuppressive tumor microenvironment and the intrinsic resistance of GBM...

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Autores: Tur-Planells, Vicent, Bykov, Yonina, Dawodu, Gloria, García-Romero, Noemi, Izpura-Luis, Sara, Pérez-Rodríguez, Leticia, Rius-Rocabert, Sergio, Palacín-Aliana, Irina, Arranz-Herrero, Javier, Márquez-Leiva, Inmaculada, Monago-Sanchez, Alvaro, Del Rio, Maria Luisa, Rodriguez-Barbosa, Jose Ignacio, Cano-Ochando, Jordi, García-Sastre, Adolfo, Lozano-Ojalvo, Daniel, Nistal-Villan, Estanislao, Ayuso-Sacido, Angel, Cuadrado-Castano, Sara
Tipo de recurso: artículo
Fecha de publicación:2025
País:España
Institución:Universidad de Málaga
Repositorio:DDFV. Repositorio Institucional de la Universidad Francisco de Vitoria
Idioma:inglés
OAI Identifier:oai:ddfv.ufv.es:10641/7087
Acceso en línea:https://hdl.handle.net/10641/7087
Access Level:acceso abierto
Palabra clave:Central Nervous System Cancer
Immunotherapy
Intratumoral
Oncolytic virus
Tumor microenvironment - TME
Immunology and Allergy
Immunology
Molecular Medicine
Oncology
Pharmacology
Cancer Research
SDG 3 - Good Health and Well-being
Yes
yes
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spelling Infectious bursal disease virus (IBDV) as a novel oncolytic virotherapy in glioblastomaTur-Planells, VicentBykov, YoninaDawodu, GloriaGarcía-Romero, NoemiIzpura-Luis, SaraPérez-Rodríguez, LeticiaRius-Rocabert, SergioPalacín-Aliana, IrinaArranz-Herrero, JavierMárquez-Leiva, InmaculadaMonago-Sanchez, AlvaroDel Rio, Maria LuisaRodriguez-Barbosa, Jose IgnacioCano-Ochando, JordiGarcía-Sastre, AdolfoLozano-Ojalvo, DanielNistal-Villan, EstanislaoAyuso-Sacido, AngelCuadrado-Castano, SaraCentral Nervous System CancerImmunotherapyIntratumoralOncolytic virusTumor microenvironment - TMEImmunology and AllergyImmunologyMolecular MedicineOncologyPharmacologyCancer ResearchSDG 3 - Good Health and Well-beingYesyesBackground Glioblastoma (GBM) is the most aggressive form of cancer of the central nervous system. Despite advances in immunotherapies and standard-of-care treatments for GBMs, clinical outcomes remain limited— owing to the immunosuppressive tumor microenvironment and the intrinsic resistance of GBM to conventional approaches. As a result, there is growing interest in rational combination strategies, particularly those pairing oncolytic viruses with immune-based therapies or established treatment modalities. Oncolytic viruses, by displaying conditionally enabled tumor cell-restricted replication, while stimulating antitumor immune responses and leaving healthy tissue unharmed, have the potential to reshape the therapeutic landscape in GBM and aid in achieving more durable benefits for patients. This study investigates the use of infectious bursal disease virus (IBDV) as a potential virotherapy for GBM. Methods and results In vitro, IBDV infects and replicates within murine GBM cells and patient-derived GBM stem cells, inducing direct oncolysis and activating proinflammatory gene expression programs. IBDV also enhances the cytolytic activity of temozolomide (TMZ) in treated GBM cells, complementing TMZ chemotherapeutic activity. In vivo, treatment with IBDV in CT-2A GBMbearing syngeneic mice significantly reduced tumor growth and improved survival compared with control mice. Intratumoral administration of IBDV induces a deep remodeling of the tumor immune microenvironment, reducing immunosuppressive M2-like macrophages and increasing the ratio of CD8+T cells to regulatory T cells. This reversion of immunosuppression linked to monocytederived macrophages has been confirmed on experimental ex vivo infections of explants derived from human GBM donors. Conclusion These findings support further consideration of IBDV as a novel virotherapeutic agent for GBM.Facultad de Ciencias Experimentales20252025-11-0420252025-11-04journal articlehttp://purl.org/coar/resource_type/c_6501info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10641/7087reponame:DDFV. Repositorio Institucional de la Universidad Francisco de Vitoriainstname:Universidad de MálagaInglésengopen accesshttp://purl.org/coar/access_right/c_abf2http://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:ddfv.ufv.es:10641/70872026-06-11T12:44:57Z
dc.title.none.fl_str_mv Infectious bursal disease virus (IBDV) as a novel oncolytic virotherapy in glioblastoma
title Infectious bursal disease virus (IBDV) as a novel oncolytic virotherapy in glioblastoma
spellingShingle Infectious bursal disease virus (IBDV) as a novel oncolytic virotherapy in glioblastoma
Tur-Planells, Vicent
Central Nervous System Cancer
Immunotherapy
Intratumoral
Oncolytic virus
Tumor microenvironment - TME
Immunology and Allergy
Immunology
Molecular Medicine
Oncology
Pharmacology
Cancer Research
SDG 3 - Good Health and Well-being
Yes
yes
title_short Infectious bursal disease virus (IBDV) as a novel oncolytic virotherapy in glioblastoma
title_full Infectious bursal disease virus (IBDV) as a novel oncolytic virotherapy in glioblastoma
title_fullStr Infectious bursal disease virus (IBDV) as a novel oncolytic virotherapy in glioblastoma
title_full_unstemmed Infectious bursal disease virus (IBDV) as a novel oncolytic virotherapy in glioblastoma
title_sort Infectious bursal disease virus (IBDV) as a novel oncolytic virotherapy in glioblastoma
dc.creator.none.fl_str_mv Tur-Planells, Vicent
Bykov, Yonina
Dawodu, Gloria
García-Romero, Noemi
Izpura-Luis, Sara
Pérez-Rodríguez, Leticia
Rius-Rocabert, Sergio
Palacín-Aliana, Irina
Arranz-Herrero, Javier
Márquez-Leiva, Inmaculada
Monago-Sanchez, Alvaro
Del Rio, Maria Luisa
Rodriguez-Barbosa, Jose Ignacio
Cano-Ochando, Jordi
García-Sastre, Adolfo
Lozano-Ojalvo, Daniel
Nistal-Villan, Estanislao
Ayuso-Sacido, Angel
Cuadrado-Castano, Sara
author Tur-Planells, Vicent
author_facet Tur-Planells, Vicent
Bykov, Yonina
Dawodu, Gloria
García-Romero, Noemi
Izpura-Luis, Sara
Pérez-Rodríguez, Leticia
Rius-Rocabert, Sergio
Palacín-Aliana, Irina
Arranz-Herrero, Javier
Márquez-Leiva, Inmaculada
Monago-Sanchez, Alvaro
Del Rio, Maria Luisa
Rodriguez-Barbosa, Jose Ignacio
Cano-Ochando, Jordi
García-Sastre, Adolfo
Lozano-Ojalvo, Daniel
Nistal-Villan, Estanislao
Ayuso-Sacido, Angel
Cuadrado-Castano, Sara
author_role author
author2 Bykov, Yonina
Dawodu, Gloria
García-Romero, Noemi
Izpura-Luis, Sara
Pérez-Rodríguez, Leticia
Rius-Rocabert, Sergio
Palacín-Aliana, Irina
Arranz-Herrero, Javier
Márquez-Leiva, Inmaculada
Monago-Sanchez, Alvaro
Del Rio, Maria Luisa
Rodriguez-Barbosa, Jose Ignacio
Cano-Ochando, Jordi
García-Sastre, Adolfo
Lozano-Ojalvo, Daniel
Nistal-Villan, Estanislao
Ayuso-Sacido, Angel
Cuadrado-Castano, Sara
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Facultad de Ciencias Experimentales
dc.subject.none.fl_str_mv Central Nervous System Cancer
Immunotherapy
Intratumoral
Oncolytic virus
Tumor microenvironment - TME
Immunology and Allergy
Immunology
Molecular Medicine
Oncology
Pharmacology
Cancer Research
SDG 3 - Good Health and Well-being
Yes
yes
topic Central Nervous System Cancer
Immunotherapy
Intratumoral
Oncolytic virus
Tumor microenvironment - TME
Immunology and Allergy
Immunology
Molecular Medicine
Oncology
Pharmacology
Cancer Research
SDG 3 - Good Health and Well-being
Yes
yes
description Background Glioblastoma (GBM) is the most aggressive form of cancer of the central nervous system. Despite advances in immunotherapies and standard-of-care treatments for GBMs, clinical outcomes remain limited— owing to the immunosuppressive tumor microenvironment and the intrinsic resistance of GBM to conventional approaches. As a result, there is growing interest in rational combination strategies, particularly those pairing oncolytic viruses with immune-based therapies or established treatment modalities. Oncolytic viruses, by displaying conditionally enabled tumor cell-restricted replication, while stimulating antitumor immune responses and leaving healthy tissue unharmed, have the potential to reshape the therapeutic landscape in GBM and aid in achieving more durable benefits for patients. This study investigates the use of infectious bursal disease virus (IBDV) as a potential virotherapy for GBM. Methods and results In vitro, IBDV infects and replicates within murine GBM cells and patient-derived GBM stem cells, inducing direct oncolysis and activating proinflammatory gene expression programs. IBDV also enhances the cytolytic activity of temozolomide (TMZ) in treated GBM cells, complementing TMZ chemotherapeutic activity. In vivo, treatment with IBDV in CT-2A GBMbearing syngeneic mice significantly reduced tumor growth and improved survival compared with control mice. Intratumoral administration of IBDV induces a deep remodeling of the tumor immune microenvironment, reducing immunosuppressive M2-like macrophages and increasing the ratio of CD8+T cells to regulatory T cells. This reversion of immunosuppression linked to monocytederived macrophages has been confirmed on experimental ex vivo infections of explants derived from human GBM donors. Conclusion These findings support further consideration of IBDV as a novel virotherapeutic agent for GBM.
publishDate 2025
dc.date.none.fl_str_mv 2025
2025-11-04
2025
2025-11-04
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/10641/7087
url https://hdl.handle.net/10641/7087
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2

http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2

http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:DDFV. Repositorio Institucional de la Universidad Francisco de Vitoria
instname:Universidad de Málaga
instname_str Universidad de Málaga
reponame_str DDFV. Repositorio Institucional de la Universidad Francisco de Vitoria
collection DDFV. Repositorio Institucional de la Universidad Francisco de Vitoria
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812429

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