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Preclinical evaluation of the gorilla-derived HAdV-B AdV-lumc007 oncolytic adenovirus 'GoraVir' for the treatment of pancreatic ductal adenocarcinoma.
- Source :
-
Molecular oncology [Mol Oncol] 2024 May; Vol. 18 (5), pp. 1245-1258. Date of Electronic Publication: 2024 Jan 24. - Publication Year :
- 2024
-
Abstract
- Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy which shows unparalleled therapeutic resistance due to its genetic and cellular heterogeneity, dense stromal tissue, and immune-suppressive tumour microenvironment. Oncolytic virotherapy has emerged as a new treatment modality which uses tumour-specific viruses to eliminate cancerous cells. Non-human primate adenoviruses of the human adenovirus B (HAdV-B) species have demonstrated considerable lytic potential in human cancer cells as well as limited preexisting neutralizing immunity in humans. Previously, we have generated a new oncolytic derivative of the gorilla-derived HAdV-B AdV-lumc007 named 'GoraVir'. Here, we show that GoraVir displays oncolytic efficacy in pancreatic cancer cells and pancreatic-cancer-associated fibroblasts. Moreover, it retains its lytic potential in monoculture and co-culture spheroids. In addition, we established the ubiquitously expressed complement receptor CD46 as the main entry receptor for GoraVir. Finally, a single intratumoural dose of GoraVir was shown to delay tumour growth in a BxPC-3 xenograft model at 10 days post-treatment. Collectively, these data demonstrate that the new gorilla-derived oncolytic adenovirus is a potent oncolytic vector candidate that targets both pancreatic cancer cells and tumour-adjacent stroma.<br /> (© 2023 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)
- Subjects :
- Humans
Animals
Cell Line, Tumor
Xenograft Model Antitumor Assays
Mice
Membrane Cofactor Protein metabolism
Membrane Cofactor Protein genetics
Mice, Nude
Adenoviruses, Human genetics
Adenoviruses, Human drug effects
Female
Adenoviridae genetics
Carcinoma, Pancreatic Ductal therapy
Carcinoma, Pancreatic Ductal drug therapy
Carcinoma, Pancreatic Ductal pathology
Pancreatic Neoplasms therapy
Pancreatic Neoplasms drug therapy
Pancreatic Neoplasms pathology
Gorilla gorilla
Oncolytic Virotherapy methods
Oncolytic Viruses genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1878-0261
- Volume :
- 18
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Molecular oncology
- Publication Type :
- Academic Journal
- Accession number :
- 38037840
- Full Text :
- https://doi.org/10.1002/1878-0261.13561