Real-time analysis of replication and activity of oncolytic viruses in pancreatic cancer
Oncolytic viruses infect and replicate in cancer cells to induce their death. They thus appear to be a promising approach in the fight against cancer. This study describes for the first time the anti-tumour activity of SG33, a veterinary vaccine strain derived from Myxoma virus. SG33 is genetically engineered to encode the ANCHOR system, a molecular beacon for tracking viral DNA by non-invasive, real-time imaging. In this work, we demonstrate that the ANCHOR system allows visualization, down to the single cell level, of very early stages of infection, and quantification of SG33 virus replication in cancer cells. In particular, we report the therapeutic efficacy of SG33 in experimental models derived from pancreatic cancer (primary patient cells, 3D tumoroids, experimental tumours), while normal pancreatic cells are spared by this virus. In vivo studies show that the virus colonises experimental tumours and affects tumour growth. This work is an essential prerequisite for the use of oncolytic viruses such as SG33 in the management of patients with pancreatic cancer. It describes a new non-invasive imaging approach for the analysis of replication and therapeutic activity of a novel oncolytic virus in preclinical models of pancreatic cancer. Ultimately, this project could lead to new theranostic strategies (detection + treatment) for pancreatic cancer patients. The team is currently investigating the molecular mechanisms that control SG33 replication and activity in pancreatic cancer cells, as well as the cell death pathways induced by viral infection.
Collaborations and acknowledgements
Toulouse National Veterinary School
Marseille Cancer Research Centre
One picture :
Real-time detection of viral replication and oncolysis (green) after infection of primary cancer cells with SG33 virus
Discover the published article
Hum Gene Ther. 2021 Jan 27.doi: 10.1089/hum.2020.294. Online ahead of print.
A novel imaging approach for single-cell, real-time analysis of oncolytic virus replication and efficacy in cancer cells
Lorraine Quillien, Sokunthea Top, Sandrine Kappler, Agathe Redouté, Nelson Dusetti, Charlotte Quentin-Froignant, Hubert Lulka, Christelle Camus, Louis Buscail, Franck Gallardo, Stéphane Bertagnoli, Pierre Cordelier
Toulouse Cancer Research Center (Oncopole)
Toulouse – FR
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