Preclinical evaluation of the gorilla-derived HAdV-B AdV-lumc007 oncolytic adenovirus 'GoraVir' for the treatment of pancreatic ductal adenocarcinoma

Sep 21, 2026

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Preclinical evaluation of the gorilla-derived oncolytic adenovirus GoraVir (HAdV-B AdV-lumc007) for pancreatic ductal adenocarcinoma addresses the disease’s resistance driven by genetic and cellular heterogeneity, dense stroma, and an immune-suppressive tumour microenvironment. The study demonstrates GoraVir oncolytic efficacy in pancreatic cancer cells and cancer-associated fibroblasts, including monoculture and co-culture spheroids. It identifies CD46 as the main entry receptor and shows delayed tumour growth after a single intratumoural dose in a BxPC-3 xenograft model.

LanguageEnglish

CategoryResearch & Report

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Pages14

Reading Time35 min

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Introduction

Abbreviations

Preclinical evaluation of the gorilla-derived HAdV-BAdV-lumc007 oncolytic adenovirus ‘GoraVir’ for the treatment of pancreatic ductal adenocarcinoma Selas T. F. Bots 1 , Tom J. Harryvan2, Christianne Groeneveldt3 , Priscilla Kinderman2, Vera Kemp 1, Nadine van Montfoort2 and Rob C. Hoeben 1 1 Department of Cell and Chemical Biology, Leiden University Medical Center, The Netherlands 2 Department of Gastroenterology and Hepatology, Leiden University Medical Center, The Netherlands 3 Department of Medical Oncology, Leiden University Medical Center, The Netherlands Keywords CD46; non-human primate oncolytic adenovirus; pancreatic ductaladenocarcinoma; tumour-stroma; xenograft model Correspondence R. C. Hoeben, Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden 2333 ZC, The Netherlands E-mail: [r.c.hoeben@lumc.nl](r.c.hoeben@lumc.nl) (Received 31 August 2022, revised 27 June 2023, accepted 29 November 2023, available online 24 January 2024) doi:10 . 1002/1878-0261 .13561 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 inhuman 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 gorilladerived oncolytic adenovirus is a potent oncolytic vector candidate that targets both pancreatic cancer cells and tumour-adjacent stroma. 1. Introduction Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with a ﬁve-year overall survival rate of around 10% (National Cancer Institute) . The majority of patients presents with unresectable, locally advanced, or metastatic disease at the time of diagnosis which prohibits curative surgery. Moreover, PDAC shows unrivalled therapeutic resistance due to its genetic and cellular heterogeneity, dense stromal tissue, and immune-suppressive tumour microenvironment (TME) [1] . The promising results of immunotherapies in other types of malignancies led to pre-clinical and clinical studies in PDAC (e.g., checkpoint inhibitors and therapeutic vaccines) both as standalone treatments as well as in combinatorial approaches [2]. Unfortunately, most of these showed only moderate improvements in survival. Hence, there is a need for improved immunotherapies that can overcome the inhibition by the immunosuppressive TME in PDAC [2] . Abbreviations CAF, cancer-associated ﬁbroblast; CAR, coxsackie and adenovirus receptor; EV, empty vector; hAd, human adenovirus; HAdV-C5, human adenovirus type 5; KO, knock-out; nhpAd, non-human primate adenovirus; OVT, oncolytic virotherapy; PDAC, pancreatic ductaladenocarcinoma; TME, tumour microenvironment; WT, wildtype. Molecular Oncology 18 (2024) 1245–1258 ª 2023 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of 1245 Federation of European Biochemical Societies. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduct

FAQs

What is the main therapeutic problem targeted by this study in pancreatic ductal adenocarcinoma (PDAC)?

PDAC is described as highly aggressive and unusually resistant to therapy due to genetic/cellular heterogeneity, dense stromal tissue, and an immune-suppressive tumour microenvironment.

What oncolytic activity does GoraVir show in pancreatic cancer models?

GoraVir displays oncolytic efficacy in pancreatic cancer cells and pancreatic-cancer-associated fibroblasts and retains lytic potential in both monoculture and co-culture spheroids.

Which receptor mediates cellular entry of GoraVir, and what in vivo effect is reported?

CD46 is established as the main entry receptor. A single intratumoural dose delays tumour growth in a BxPC-3 xenograft model at 10 days post-treatment.

Sep 21, 2026

Uploaded by Aurora