Exploiting 4-1BB immune checkpoint to enhance the efficacy of oncolytic virotherapy for diffuse intrinsic pontine gliomas

Diffuse intrinsic pontine gliomas (DIPGs) are aggressive pediatric brain tumors, and patient survival has not changed despite many therapeutic efforts, emphasizing the urgent need for effective treatments. Here, we evaluated the anti-DIPG effect of the oncolytic adenovirus Delta-24-ACT, which was en...

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Detalhes bibliográficos
Autores: Laspidea, V. (Virginia)|||/items/16d4f649-0742-47dc-a391-881d6cfb978f, Puigdelloses-Vallcorba, M. (Montserrat)|||/items/658120d0-6a3c-4bf3-9446-33a9234f787e, Labiano-Almiñana, S. (Sara)|||/items/65de3442-2f0f-4c20-8e40-43525bb58657, Marrodán-Fernández, L. (Lucía)|||/items/cb588714-8640-4468-a1e4-ea467d9fe714, Garcia-Moure, M. (Marc)|||/items/9741d07b-2525-4e98-9bfc-93fc3e869273, Zalacain-Díez, M. (Marta)|||/items/c9a0a606-4b28-4f43-b423-2bd8ca984432, Gonzalez-Huarriz, M. (Marisol)|||/items/00a6d7fb-7851-4264-bdfd-9172d60bc40b, Martinez-Velez, N. (Naiara)|||/items/691b094b-c17c-4084-be40-caea58286559, Ausejo-Mauleón, I. (Iker)|||/items/5dc64e9f-8695-4947-a007-886bda06f2a5, Nava-Martín, D. (Daniel) de la|||/items/9d3a254f-7e46-4632-8066-48e55de9acbd, Herrador-Cañete, G. (Guillermo)|||/items/91f6f4a9-1383-4ec6-b17f-a914248ff8b0, Marco-Sanz, J. (Javier)|||/items/9946fc39-972a-4848-982e-500d4c384941, Guruceaga-Martínez, E. (Elizabeth)|||/items/71d8df8b-4fab-4004-a38e-4057dddc85b2, Andrea, C.E. (Carlos Eduardo) de|||/items/e487698b-8d56-4c3e-8cba-40e33c78083a, Villalba, M. (María)|||/items/7f65b092-d480-4953-a790-65baf0bb567d, Becher, O.J. (Oren J.)|||/items/8218a203-30af-4259-a7fc-91aa4e2c1faa, Squatrito, M. (Massimo)|||/items/ad30f998-b6e1-49e4-b9f9-2d63b69bf1bf, Matía, V. (Verónica)|||/items/6ef26b98-81f3-407f-9f88-de01013363ac, Gallego-Perez-Larraya, J. (Jaime)|||/items/8a92f20a-1e24-427d-8da0-ace4eba5620d, Patiño-García, A. (Ana)|||/items/d68c74f1-df22-4e04-9b77-9cf48fd87b46, Gupta, S. (Sumit)|||/items/24fbd7fb-98ec-48b5-a608-d9e9b6fa69d9, Gomez-Manzano, C. (Candelaria)|||/items/5e8d7495-6be8-46e1-8303-cfd722d30166, Fueyo, J. (Juan)|||/items/a4e5ff79-2565-4461-ab26-34868ff5ff4d, Alonso-Roldán, M.M. (Marta María)|||/items/b912e21e-f895-4efe-bc4c-de1ca8f36c37
Formato: artículo
Fecha de publicación:2022
País:España
Recursos:Universidad de Navarra
Repositorio:Dadun. Depósito Académico Digital de la Universidad de Navarra
Idioma:inglés
OAI Identifier:oai:dadun.unav.edu:10171/116491
Acesso em linha:https://hdl.handle.net/10171/116491
Access Level:acceso abierto
Palavra-chave:Brain cancer
Cancer immunotherapy
Immunology
Immunotherapy
Oncology
Descrição
Resumo:Diffuse intrinsic pontine gliomas (DIPGs) are aggressive pediatric brain tumors, and patient survival has not changed despite many therapeutic efforts, emphasizing the urgent need for effective treatments. Here, we evaluated the anti-DIPG effect of the oncolytic adenovirus Delta-24-ACT, which was engineered to express the costimulatory ligand 4-1BBL to potentiate the antitumor immune response of the virus. Delta-24-ACT induced the expression of functional 4-1BBL on the membranes of infected DIPG cells, which enhanced the costimulation of CD8+ T lymphocytes. In vivo, Delta-24-ACT treatment of murine DIPG orthotopic tumors significantly improved the survival of treated mice, leading to long-term survivors that developed immunological memory against these tumors. In addition, Delta-24-ACT was safe and caused no local or systemic toxicity. Mechanistic studies showed that Delta-24-ACT modulated the tumor-immune content, not only increasing the number, but also improving the functionality of immune cells. All of these data highlight the safety and potential therapeutic benefit of Delta-24-ACT the treatment of patients with DIPG.

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