Investigation of an oncolytic herpes simplex virus as a potential therapeutic agent for gastroenteropancreatic neuroendocrine neoplasms

Abstract Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) present unique challenges due to their heterogeneity and limited treatment options. Oncolytic virotherapy has emerged as a promising therapeutic for other NETs and thus, we sought to investigate the potential of an engineered oncolytic...

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Main Authors: Colin H. Quinn, Janet R. Julson, Michael H. Erwin, Hooper R. Markert, Larua V. Bownes, Jerry E. Stewart, Sorina Shirley, Karina J. Yoon, Jamie M. Aye, James M. Markert, Elizabeth A. Beierle
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Language:English
Published: Nature Portfolio 2025-04-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-98588-7
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author Colin H. Quinn
Janet R. Julson
Michael H. Erwin
Hooper R. Markert
Larua V. Bownes
Jerry E. Stewart
Sorina Shirley
Karina J. Yoon
Jamie M. Aye
James M. Markert
Elizabeth A. Beierle
author_facet Colin H. Quinn
Janet R. Julson
Michael H. Erwin
Hooper R. Markert
Larua V. Bownes
Jerry E. Stewart
Sorina Shirley
Karina J. Yoon
Jamie M. Aye
James M. Markert
Elizabeth A. Beierle
author_sort Colin H. Quinn
collection DOAJ
description Abstract Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) present unique challenges due to their heterogeneity and limited treatment options. Oncolytic virotherapy has emerged as a promising therapeutic for other NETs and thus, we sought to investigate the potential of an engineered oncolytic herpes simplex virus (oHSV), M002, for GEP-NETS. We employed an established long-term passage GEP-NET cell line and a unique, human pediatric patient-derived xenograft GEP-NET line. We found the virus to effectively infect, replicate within, and kill both cell lines in vitro. Similar effects were noted in vivo, with M002 decreasing tumor growth and improving overall survival in mice bearing tumors from both the established cell line and human GEP-NET PDX. Overall, these studies provide an evaluation of an oncolytic HSV in GEP-NETs, highlighting its therapeutic potential and considerations for clinical translation.
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spelling doaj-art-b54d78e513df41e9be4676ea0d9e7fad2025-08-20T03:18:32ZengNature PortfolioScientific Reports2045-23222025-04-0115111010.1038/s41598-025-98588-7Investigation of an oncolytic herpes simplex virus as a potential therapeutic agent for gastroenteropancreatic neuroendocrine neoplasmsColin H. Quinn0Janet R. Julson1Michael H. Erwin2Hooper R. Markert3Larua V. Bownes4Jerry E. Stewart5Sorina Shirley6Karina J. Yoon7Jamie M. Aye8James M. Markert9Elizabeth A. Beierle10Division of Pediatric Surgery, Department of Surgery, University of Alabama at BirminghamDivision of Pediatric Surgery, Department of Surgery, University of Alabama at BirminghamDivision of Pediatric Surgery, Department of Surgery, University of Alabama at BirminghamDivision of Pediatric Surgery, Department of Surgery, University of Alabama at BirminghamDivision of Pediatric Surgery, Department of Surgery, University of Alabama at BirminghamDivision of Pediatric Surgery, Department of Surgery, University of Alabama at BirminghamDivision of Pediatric Surgery, Department of Surgery, University of Alabama at BirminghamDepartment of Cell, Developmental and Integrative Biology, University of Alabama at BirminghamDivision of Hematology Oncology, Department of Pediatrics, University of Alabama at BirminghamDepartment of Neurosurgery, University of Alabama at BirminghamDivision of Pediatric Surgery, Department of Surgery, University of Alabama at BirminghamAbstract Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) present unique challenges due to their heterogeneity and limited treatment options. Oncolytic virotherapy has emerged as a promising therapeutic for other NETs and thus, we sought to investigate the potential of an engineered oncolytic herpes simplex virus (oHSV), M002, for GEP-NETS. We employed an established long-term passage GEP-NET cell line and a unique, human pediatric patient-derived xenograft GEP-NET line. We found the virus to effectively infect, replicate within, and kill both cell lines in vitro. Similar effects were noted in vivo, with M002 decreasing tumor growth and improving overall survival in mice bearing tumors from both the established cell line and human GEP-NET PDX. Overall, these studies provide an evaluation of an oncolytic HSV in GEP-NETs, highlighting its therapeutic potential and considerations for clinical translation.https://doi.org/10.1038/s41598-025-98588-7Neuroendocrine tumorsOncolytic virusPatient derived xenograftsTranslational research
spellingShingle Colin H. Quinn
Janet R. Julson
Michael H. Erwin
Hooper R. Markert
Larua V. Bownes
Jerry E. Stewart
Sorina Shirley
Karina J. Yoon
Jamie M. Aye
James M. Markert
Elizabeth A. Beierle
Investigation of an oncolytic herpes simplex virus as a potential therapeutic agent for gastroenteropancreatic neuroendocrine neoplasms
Scientific Reports
Neuroendocrine tumors
Oncolytic virus
Patient derived xenografts
Translational research
title Investigation of an oncolytic herpes simplex virus as a potential therapeutic agent for gastroenteropancreatic neuroendocrine neoplasms
title_full Investigation of an oncolytic herpes simplex virus as a potential therapeutic agent for gastroenteropancreatic neuroendocrine neoplasms
title_fullStr Investigation of an oncolytic herpes simplex virus as a potential therapeutic agent for gastroenteropancreatic neuroendocrine neoplasms
title_full_unstemmed Investigation of an oncolytic herpes simplex virus as a potential therapeutic agent for gastroenteropancreatic neuroendocrine neoplasms
title_short Investigation of an oncolytic herpes simplex virus as a potential therapeutic agent for gastroenteropancreatic neuroendocrine neoplasms
title_sort investigation of an oncolytic herpes simplex virus as a potential therapeutic agent for gastroenteropancreatic neuroendocrine neoplasms
topic Neuroendocrine tumors
Oncolytic virus
Patient derived xenografts
Translational research
url https://doi.org/10.1038/s41598-025-98588-7
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