Preclinical Evaluation of the Gorilla-derived HAdV-B AdV-lumc007 Oncolytic Adenovirus 'GoraVir' for the Treatment of Pancreatic Ductal Adenocarcinoma

Overview

Journal Mol Oncol

Specialties Molecular Biology
Oncology

Date 2023 Dec 1

PMID 38037840

Authors

Selas T F Bots

Tom J Harryvan

Christianne Groeneveldt

Priscilla Kinderman

Vera Kemp

Nadine van Montfoort

Rob C Hoeben

Affiliations

Soon will be listed here.

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.

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