The heterogeneous sensitivity of pediatric brain tumors to different oncolytic viruses is predicted by unique gene expression profiles
Despite decades of research, the prognosis of high-grade pediatric brain tumors (PBTs) remains dismal; however, recent cases of favorable clinical responses were documented in clinical trials using oncolytic viruses (OVs). In the current study, we employed four different species of OVs: adenovirus D...
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| Language: | English |
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Elsevier
2024-06-01
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| Series: | Molecular Therapy: Oncology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2950329924000468 |
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| author | Konstantinos Vazaios Εftychia Stavrakaki Lisette B. Vogelezang Jie Ju Piotr Waranecki Dennis S. Metselaar Michaël H. Meel Vera Kemp Bernadette G. van den Hoogen Rob C. Hoeben E. Antonio Chiocca William F. Goins Andrew Stubbs Yunlei Li Marta M. Alonso Friso G. Calkoen Esther Hulleman Jasper van der Lugt Martine L.M. Lamfers |
| author_facet | Konstantinos Vazaios Εftychia Stavrakaki Lisette B. Vogelezang Jie Ju Piotr Waranecki Dennis S. Metselaar Michaël H. Meel Vera Kemp Bernadette G. van den Hoogen Rob C. Hoeben E. Antonio Chiocca William F. Goins Andrew Stubbs Yunlei Li Marta M. Alonso Friso G. Calkoen Esther Hulleman Jasper van der Lugt Martine L.M. Lamfers |
| author_sort | Konstantinos Vazaios |
| collection | DOAJ |
| description | Despite decades of research, the prognosis of high-grade pediatric brain tumors (PBTs) remains dismal; however, recent cases of favorable clinical responses were documented in clinical trials using oncolytic viruses (OVs). In the current study, we employed four different species of OVs: adenovirus Delta24-RGD, herpes simplex virus rQNestin34.5v1, reovirus R124, and the non-virulent Newcastle disease virus rNDV-F0-GFP against three entities of PBTs (high-grade gliomas, atypical teratoid/rhabdoid tumors, and ependymomas) to determine their in vitro efficacy. These four OVs were screened on 14 patient-derived PBT cell cultures and the degree of oncolysis was assessed using an ATP-based assay. Subsequently, the observed viral efficacies were correlated to whole transcriptome data and Gene Ontology analysis was performed. Although no significant tumor type-specific OV efficacy was observed, the analysis revealed the intrinsic biological processes that associated with OV efficacy. The predictive power of the identified expression profiles was further validated in vitro by screening additional PBTs. In summary, our results demonstrate OV susceptibility of multiple patient-derived PBT entities and the ability to predict in vitro responses to OVs using unique expression profiles. Such profiles may hold promise for future OV preselection with effective oncolytic potency in a specific tumor, therewith potentially improving OV responses. |
| format | Article |
| id | doaj-art-4f89f9ae6af94262a419f5c33cbc8f5b |
| institution | Kabale University |
| issn | 2950-3299 |
| language | English |
| publishDate | 2024-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Oncology |
| spelling | doaj-art-4f89f9ae6af94262a419f5c33cbc8f5b2024-11-24T04:15:35ZengElsevierMolecular Therapy: Oncology2950-32992024-06-01322200804The heterogeneous sensitivity of pediatric brain tumors to different oncolytic viruses is predicted by unique gene expression profilesKonstantinos Vazaios0Εftychia Stavrakaki1Lisette B. Vogelezang2Jie Ju3Piotr Waranecki4Dennis S. Metselaar5Michaël H. Meel6Vera Kemp7Bernadette G. van den Hoogen8Rob C. Hoeben9E. Antonio Chiocca10William F. Goins11Andrew Stubbs12Yunlei Li13Marta M. Alonso14Friso G. Calkoen15Esther Hulleman16Jasper van der Lugt17Martine L.M. Lamfers18Princess Máxima Center for Pediatric Oncology, Heidelberglaan 25, 3584 CS Utrecht, the Netherlands; Department of Neurosurgery, Brain Tumor Center, Erasmus Medical Center, Dr. Molewaterplein 40, 3015 GD Rotterdam, the Netherlands; Center for Translational Immunology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, the NetherlandsDepartment of Neurosurgery, Brain Tumor Center, Erasmus Medical Center, Dr. Molewaterplein 40, 3015 GD Rotterdam, the NetherlandsDepartment of Neurosurgery, Brain Tumor Center, Erasmus Medical Center, Dr. Molewaterplein 40, 3015 GD Rotterdam, the NetherlandsDepartment of Pathology and Clinical Bioinformatics, Erasmus Medical Center, Dr. Molewaterplein 40, 3015 GD Rotterdam, the NetherlandsPrincess Máxima Center for Pediatric Oncology, Heidelberglaan 25, 3584 CS Utrecht, the NetherlandsPrincess Máxima Center for Pediatric Oncology, Heidelberglaan 25, 3584 CS Utrecht, the NetherlandsPrincess Máxima Center for Pediatric Oncology, Heidelberglaan 25, 3584 CS Utrecht, the Netherlands; Department of Pediatrics, Wilhelmina Children’s Hospital, University Medical Center Utrecht, Lundlaan 6, 3584 EA Utrecht, the NetherlandsDepartment of Cell and Chemical Biology, Leiden University Medical Center, Einthovenweg 20, 2333 ZC Leiden, the NetherlandsDepartment of Viroscience, Erasmus Medical Center, Dr. Molewaterplein 40, 3015 GD Rotterdam, the NetherlandsDepartment of Cell and Chemical Biology, Leiden University Medical Center, Einthovenweg 20, 2333 ZC Leiden, the NetherlandsDepartment of Neurosurgery, Brigham and Women’s Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USADepartment of Microbiology & Molecular Genetics, University of Pittsburgh School of Medicine, 450 Technology Dr, Pittsburgh, PA 15219, USADepartment of Pathology and Clinical Bioinformatics, Erasmus Medical Center, Dr. Molewaterplein 40, 3015 GD Rotterdam, the NetherlandsDepartment of Pathology and Clinical Bioinformatics, Erasmus Medical Center, Dr. Molewaterplein 40, 3015 GD Rotterdam, the NetherlandsProgram in Solid Tumors, Center for Applied Medical Research (CIMA), Avda. de Pío XII, 55, 31008 Pamplona, Spain; Department of Pediatrics, Clínica Universidad de Navarra, Av. de Pío XII, 36, 31008 Pamplona, Spain; Health Research Institute of Navarra (IDISNA), Av. de Pío XII, 36, 31008 Pamplona, SpainPrincess Máxima Center for Pediatric Oncology, Heidelberglaan 25, 3584 CS Utrecht, the NetherlandsPrincess Máxima Center for Pediatric Oncology, Heidelberglaan 25, 3584 CS Utrecht, the NetherlandsPrincess Máxima Center for Pediatric Oncology, Heidelberglaan 25, 3584 CS Utrecht, the Netherlands; Corresponding author: Jasper van der Lugt, MD, PhD, Princess Máxima Center for Pediatric Oncology, Heidelberglaan 25, 3585 CS Utrecht, the Netherlands.Department of Neurosurgery, Brain Tumor Center, Erasmus Medical Center, Dr. Molewaterplein 40, 3015 GD Rotterdam, the NetherlandsDespite decades of research, the prognosis of high-grade pediatric brain tumors (PBTs) remains dismal; however, recent cases of favorable clinical responses were documented in clinical trials using oncolytic viruses (OVs). In the current study, we employed four different species of OVs: adenovirus Delta24-RGD, herpes simplex virus rQNestin34.5v1, reovirus R124, and the non-virulent Newcastle disease virus rNDV-F0-GFP against three entities of PBTs (high-grade gliomas, atypical teratoid/rhabdoid tumors, and ependymomas) to determine their in vitro efficacy. These four OVs were screened on 14 patient-derived PBT cell cultures and the degree of oncolysis was assessed using an ATP-based assay. Subsequently, the observed viral efficacies were correlated to whole transcriptome data and Gene Ontology analysis was performed. Although no significant tumor type-specific OV efficacy was observed, the analysis revealed the intrinsic biological processes that associated with OV efficacy. The predictive power of the identified expression profiles was further validated in vitro by screening additional PBTs. In summary, our results demonstrate OV susceptibility of multiple patient-derived PBT entities and the ability to predict in vitro responses to OVs using unique expression profiles. Such profiles may hold promise for future OV preselection with effective oncolytic potency in a specific tumor, therewith potentially improving OV responses.http://www.sciencedirect.com/science/article/pii/S2950329924000468MT: Regular Issuepediatric brain tumorsoncolytic virusessensitivityresistanceGene Ontology |
| spellingShingle | Konstantinos Vazaios Εftychia Stavrakaki Lisette B. Vogelezang Jie Ju Piotr Waranecki Dennis S. Metselaar Michaël H. Meel Vera Kemp Bernadette G. van den Hoogen Rob C. Hoeben E. Antonio Chiocca William F. Goins Andrew Stubbs Yunlei Li Marta M. Alonso Friso G. Calkoen Esther Hulleman Jasper van der Lugt Martine L.M. Lamfers The heterogeneous sensitivity of pediatric brain tumors to different oncolytic viruses is predicted by unique gene expression profiles Molecular Therapy: Oncology MT: Regular Issue pediatric brain tumors oncolytic viruses sensitivity resistance Gene Ontology |
| title | The heterogeneous sensitivity of pediatric brain tumors to different oncolytic viruses is predicted by unique gene expression profiles |
| title_full | The heterogeneous sensitivity of pediatric brain tumors to different oncolytic viruses is predicted by unique gene expression profiles |
| title_fullStr | The heterogeneous sensitivity of pediatric brain tumors to different oncolytic viruses is predicted by unique gene expression profiles |
| title_full_unstemmed | The heterogeneous sensitivity of pediatric brain tumors to different oncolytic viruses is predicted by unique gene expression profiles |
| title_short | The heterogeneous sensitivity of pediatric brain tumors to different oncolytic viruses is predicted by unique gene expression profiles |
| title_sort | heterogeneous sensitivity of pediatric brain tumors to different oncolytic viruses is predicted by unique gene expression profiles |
| topic | MT: Regular Issue pediatric brain tumors oncolytic viruses sensitivity resistance Gene Ontology |
| url | http://www.sciencedirect.com/science/article/pii/S2950329924000468 |
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