دورية أكاديمية
أعرض في EDS

The oncolytic adenovirus Delta-24-RGD in combination with ONC201 induces a potent antitumor response in pediatric high-grade and diffuse midline glioma models.

التفاصيل البيبلوغرافية
العنوان: The oncolytic adenovirus Delta-24-RGD in combination with ONC201 induces a potent antitumor response in pediatric high-grade and diffuse midline glioma models.
المؤلفون: de la Nava D; Department of Pediatrics, Clínica Universidad de Navarra, Pamplona, Spain.; Solid Tumor Program, Center for the Applied Medical Research, Pamplona, Spain.; Health Research Institute of Navarra (IdiSNA), Pamplona, Spain., Ausejo-Mauleon I; Department of Pediatrics, Clínica Universidad de Navarra, Pamplona, Spain.; Solid Tumor Program, Center for the Applied Medical Research, Pamplona, Spain.; Health Research Institute of Navarra (IdiSNA), Pamplona, Spain., Laspidea V; Department of Pediatrics, Clínica Universidad de Navarra, Pamplona, Spain.; Solid Tumor Program, Center for the Applied Medical Research, Pamplona, Spain.; Health Research Institute of Navarra (IdiSNA), Pamplona, Spain., Gonzalez-Huarriz M; Department of Pediatrics, Clínica Universidad de Navarra, Pamplona, Spain.; Solid Tumor Program, Center for the Applied Medical Research, Pamplona, Spain.; Health Research Institute of Navarra (IdiSNA), Pamplona, Spain., Lacalle A; Department of Pediatrics, Clínica Universidad de Navarra, Pamplona, Spain.; Solid Tumor Program, Center for the Applied Medical Research, Pamplona, Spain.; Health Research Institute of Navarra (IdiSNA), Pamplona, Spain., Casares N; Department of Pediatrics, Clínica Universidad de Navarra, Pamplona, Spain.; Solid Tumor Program, Center for the Applied Medical Research, Pamplona, Spain.; Health Research Institute of Navarra (IdiSNA), Pamplona, Spain., Zalacain M; Department of Pediatrics, Clínica Universidad de Navarra, Pamplona, Spain.; Solid Tumor Program, Center for the Applied Medical Research, Pamplona, Spain.; Health Research Institute of Navarra (IdiSNA), Pamplona, Spain., Marrodan L; Department of Pediatrics, Clínica Universidad de Navarra, Pamplona, Spain.; Solid Tumor Program, Center for the Applied Medical Research, Pamplona, Spain.; Health Research Institute of Navarra (IdiSNA), Pamplona, Spain., García-Moure M; Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.; Department of Pediatrics, Clínica Universidad de Navarra, Pamplona, Spain.; Solid Tumor Program, Center for the Applied Medical Research, Pamplona, Spain.; Health Research Institute of Navarra (IdiSNA), Pamplona, Spain., Ochoa MC; Department of Pediatrics, Clínica Universidad de Navarra, Pamplona, Spain.; Solid Tumor Program, Center for the Applied Medical Research, Pamplona, Spain.; Health Research Institute of Navarra (IdiSNA), Pamplona, Spain., Tallon-Cobos AC; Solid Tumor Program, Center for the Applied Medical Research, Pamplona, Spain.; Health Research Institute of Navarra (IdiSNA), Pamplona, Spain., Hernandez-Osuna R; Department of Pediatrics, Clínica Universidad de Navarra, Pamplona, Spain.; Solid Tumor Program, Center for the Applied Medical Research, Pamplona, Spain.; Health Research Institute of Navarra (IdiSNA), Pamplona, Spain., Marco-Sanz J; Department of Pediatrics, Clínica Universidad de Navarra, Pamplona, Spain.; Solid Tumor Program, Center for the Applied Medical Research, Pamplona, Spain.; Health Research Institute of Navarra (IdiSNA), Pamplona, Spain., Dhandapani L; Department of Pediatrics, Clínica Universidad de Navarra, Pamplona, Spain.; Solid Tumor Program, Center for the Applied Medical Research, Pamplona, Spain.; Health Research Institute of Navarra (IdiSNA), Pamplona, Spain., Hervás-Corpión I; Department of Pediatrics, Clínica Universidad de Navarra, Pamplona, Spain.; Solid Tumor Program, Center for the Applied Medical Research, Pamplona, Spain.; Health Research Institute of Navarra (IdiSNA), Pamplona, Spain., Becher OJ; Jack Martin Fund Division of Pediatric Hematology-oncology, Mount Sinai, New York, USA., Nazarian J; Division of Oncology and Children's Research Center, DIPG/DMG Research Center Zurich, University Children's Hospital Zurich, Zurich, Switzerland.; Virginia Tech University, Washington, District of Columbia, USA.; Children's National Health System, Center for Genetic Medicine Research, Washington, District of Columbia, USA., Mueller S; University of California, San Francisco San Francisco, California, USA.; Division of Oncology and Children's Research Center, DIPG/DMG Research Center Zurich, University Children's Hospital Zurich, Zurich, Switzerland., Phoenix TN; Division of Pharmaceutical Sciences, James L. Winkle College of Pharmacy, University of Cincinnati, Cincinnati, Ohio, USA., van der Lugt J; Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands., Hernaez M; Bioinformatics Platform, Center for Applied Medical Research, University of Navarra (CIMA), Pamplona, Spain.; Health Research Institute of Navarra (IdiSNA), Pamplona, Spain., Guruceaga E; Bioinformatics Platform, Center for Applied Medical Research, University of Navarra (CIMA), Pamplona, Spain.; Health Research Institute of Navarra (IdiSNA), Pamplona, Spain., Koschmann C; Department of Pediatrics, University of Michigan, Ann Arbor, Michigan, USA., Venneti S; Department of Pediatrics, University of Michigan, Ann Arbor, Michigan, USA., Allen JE; Chimerix, Inc. Durham, North Carolina, USA., Dun MD; Paediatric Stream, Mark Hughes Foundation Centre for Brain Cancer Research, College of Health, Medicine, and Wellbeing, Callaghan, New South Wales, Australia.; Precision Medicine Research Program, Hunter Medical Research Institute, New Lambton Heights, New South Wales, Australia.; Cancer Signalling Research Group, School of Biomedical Sciences and Pharmacy, College of Health, Medicine and Wellbeing, University of Newcastle, Callaghan, New South Wales, Australia., Fueyo J; Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA., Gomez-Manzano C; Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA., Gallego Perez-Larraya J; Department of Neurology, Clínica Universidad de Navarra, Pamplona, Spain.; Solid Tumor Program, Center for the Applied Medical Research, Pamplona, Spain.; Health Research Institute of Navarra (IdiSNA), Pamplona, Spain., Patiño-García A; Department of Pediatrics, Clínica Universidad de Navarra, Pamplona, Spain.; Solid Tumor Program, Center for the Applied Medical Research, Pamplona, Spain.; Health Research Institute of Navarra (IdiSNA), Pamplona, Spain., Labiano S; Department of Pediatrics, Clínica Universidad de Navarra, Pamplona, Spain.; Solid Tumor Program, Center for the Applied Medical Research, Pamplona, Spain.; Health Research Institute of Navarra (IdiSNA), Pamplona, Spain., Alonso MM; Department of Pediatrics, Clínica Universidad de Navarra, Pamplona, Spain.; Solid Tumor Program, Center for the Applied Medical Research, Pamplona, Spain.; Health Research Institute of Navarra (IdiSNA), Pamplona, Spain.
المصدر: Neuro-oncology [Neuro Oncol] 2024 Aug 05; Vol. 26 (8), pp. 1509-1525.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Oxford University Press Country of Publication: England NLM ID: 100887420 Publication Model: Print Cited Medium: Internet ISSN: 1523-5866 (Electronic) Linking ISSN: 15228517 NLM ISO Abbreviation: Neuro Oncol Subsets: MEDLINE
أسماء مطبوعة: Publication: 2010- : Oxford : Oxford University Press
Original Publication: 1999-<2002> : Charlottesville, VA : Carden Jennings Pub.,
مواضيع طبية MeSH: Oncolytic Virotherapy*/methods , Glioma*/therapy , Glioma*/pathology , Glioma*/virology , Brain Neoplasms*/therapy , Brain Neoplasms*/pathology , Brain Neoplasms*/virology , Brain Neoplasms*/drug therapy , Xenograft Model Antitumor Assays*, Animals ; Humans ; Mice ; Tumor Microenvironment ; Adenoviridae/genetics ; Combined Modality Therapy ; Oncolytic Viruses ; Tumor Cells, Cultured ; Child ; Virus Replication
مستخلص: Background: Pediatric high-grade gliomas (pHGGs), including diffuse midline gliomas (DMGs), are aggressive pediatric tumors with one of the poorest prognoses. Delta-24-RGD and ONC201 have shown promising efficacy as single agents for these tumors. However, the combination of both agents has not been evaluated.
Methods: The production of functional viruses was assessed by immunoblotting and replication assays. The antitumor effect was evaluated in a panel of human and murine pHGG and DMG cell lines. RNAseq, the seahorse stress test, mitochondrial DNA content, and γH2A.X immunofluorescence were used to perform mechanistic studies. Mouse models of both diseases were used to assess the efficacy of the combination in vivo. The tumor immune microenvironment was evaluated using flow cytometry, RNAseq, and multiplexed immunofluorescence staining.
Results: The Delta-24-RGD/ONC201 combination did not affect the virus replication capability in human pHGG and DMG models in vitro. Cytotoxicity analysis showed that the combination treatment was either synergistic or additive. Mechanistically, the combination treatment increased nuclear DNA damage and maintained the metabolic perturbation and mitochondrial damage caused by each agent alone. Delta-24-RGD/ONC201 cotreatment extended the overall survival of mice implanted with human and murine pHGG and DMG cells, independent of H3 mutation status and location. Finally, combination treatment in murine DMG models revealed a reshaping of the tumor microenvironment to a proinflammatory phenotype.
Conclusions: The Delta-24-RGD/ONC201 combination improved the efficacy compared to each agent alone in in vitro and in vivo models by potentiating nuclear DNA damage and in turn improving the antitumor (immune) response to each agent alone.
(© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.)
References: Sci Signal. 2016 Feb 16;9(415):ra18. (PMID: 26884600)
Cell Cycle. 2018;17(4):468-478. (PMID: 29157092)
Nat Commun. 2019 Nov 19;10(1):5221. (PMID: 31745082)
J Virol. 2011 May;85(9):4135-42. (PMID: 21345950)
PLoS One. 2015 Mar 06;10(3):e0118926. (PMID: 25748921)
Nat Rev Neurol. 2022 Sep;18(9):515-529. (PMID: 35729337)
Nat Rev Drug Discov. 2015 Sep;14(9):642-62. (PMID: 26323545)
Am J Cancer Res. 2023 Jan 15;13(1):307-325. (PMID: 36777502)
N Engl J Med. 2021 Apr 29;384(17):1613-1622. (PMID: 33838625)
J Clin Invest. 2018 Jun 1;128(6):2325-2338. (PMID: 29533922)
J Natl Cancer Inst. 2003 May 7;95(9):652-60. (PMID: 12734316)
Mol Cell Biol. 2009 Mar;29(6):1538-53. (PMID: 19139271)
Clin Cancer Res. 2017 Aug 1;23(15):4163-4169. (PMID: 28331050)
Virus Res. 1989 Dec;14(4):339-46. (PMID: 2560294)
J Clin Oncol. 2018 Jul 1;36(19):1963-1972. (PMID: 29746225)
Neuro Oncol. 2011 Oct;13(10):1049-58. (PMID: 21784756)
Bioinformatics. 2022 Jan 12;38(3):785-791. (PMID: 34636837)
Neuro Oncol. 2023 Aug 3;25(8):1530-1545. (PMID: 36808285)
Cancer Cell. 2017 Oct 9;32(4):520-537.e5. (PMID: 28966033)
Clin Cancer Res. 2021 Mar 15;27(6):1807-1820. (PMID: 33376098)
Sci Signal. 2016 Feb 16;9(415):ra17. (PMID: 26884599)
Cancer Discov. 2023 Jan 9;13(1):114-131. (PMID: 36259971)
Nat Commun. 2019 May 28;10(1):2235. (PMID: 31138805)
Nat Med. 2023 Jun;29(6):1370-1378. (PMID: 37188783)
Cancer Cell. 2019 May 13;35(5):721-737.e9. (PMID: 31056398)
Neuro Oncol. 2020 Jan 11;22(1):94-102. (PMID: 31702782)
Cancer Res. 2007 May 1;67(9):4010-5. (PMID: 17483311)
Neuro Oncol. 2024 May 3;26(Supplement_2):S136-S154. (PMID: 37589388)
Radiother Oncol. 2021 Aug;161:140-147. (PMID: 34097975)
Cancer Discov. 2022 Feb;12(2):331-355. (PMID: 34921008)
Neuro Oncol. 2017 Sep 1;19(9):1279-1280. (PMID: 28821206)
Nucleic Acids Res. 2022 Jul 5;50(W1):W739-W743. (PMID: 35580060)
Eur J Immunol. 2021 May;51(5):1246-1261. (PMID: 33442873)
PLoS One. 2013 Oct 02;8(10):e77639. (PMID: 24098593)
Neuro Oncol. 2022 Sep 1;24(9):1438-1451. (PMID: 35157764)
J Neurooncol. 2018 Mar;137(1):103-110. (PMID: 29204840)
Neuro Oncol. 2022 Jul 1;24(7):1150-1163. (PMID: 34964902)
Neuro Oncol. 2022 Oct 5;24(Suppl 5):v1-v95. (PMID: 36196752)
Neurooncol Adv. 2021 Nov 19;3(1):vdab169. (PMID: 34988452)
Neurooncol Adv. 2022 May 24;4(1):vdac079. (PMID: 35733514)
Am J Cancer Res. 2022 Feb 15;12(2):729-743. (PMID: 35261798)
Acta Neuropathol Commun. 2022 May 31;10(1):80. (PMID: 35642016)
J Clin Oncol. 2018 May 10;36(14):1419-1427. (PMID: 29432077)
N Engl J Med. 2022 Jun 30;386(26):2471-2481. (PMID: 35767439)
Nat Rev Clin Oncol. 2011 Jun 28;8(9):540-9. (PMID: 21709698)
Clin Cancer Res. 2022 May 2;28(9):1773-1782. (PMID: 35022321)
J Immunother Cancer. 2019 May 22;7(1):136. (PMID: 31118108)
Cancer Res. 2023 May 17;:OF1-OF17. (PMID: 37195023)
J Exp Clin Cancer Res. 2018 Jan 22;37(1):11. (PMID: 29357916)
Acta Neuropathol Commun. 2019 Apr 29;7(1):64. (PMID: 31036068)
Cancer Discov. 2023 Nov 1;13(11):2370-2393. (PMID: 37584601)
Neuro Oncol. 2017 Feb 1;19(2):153-161. (PMID: 27282398)
Nature. 2022 Mar;603(7903):934-941. (PMID: 35130560)
PLoS One. 2011;6(6):e20731. (PMID: 21677778)
معلومات مُعتمدة: R01 CA261926 United States CA NCI NIH HHS; R01 NS110572 United States NS NINDS NIH HHS; R01 NS127799 United States NS NINDS NIH HHS; FI20/00020 Instituto de Salud Carlos III; FPU21/00603 Gobierno de Navarra; 817884 International ERC_ European Research Council
فهرسة مساهمة: Keywords: DMGs; Delta-24-RGD; ONC201; immunovirotherapy; pHGGs
تواريخ الأحداث: Date Created: 20240330 Date Completed: 20240805 Latest Revision: 20240807
رمز التحديث: 20240807
مُعرف محوري في PubMed: PMC11300018
DOI: 10.1093/neuonc/noae066
PMID: 38554031
قاعدة البيانات: MEDLINE
الوصف
تدمد:1523-5866
DOI:10.1093/neuonc/noae066