Carrier cell‐mediated delivery of oncolytic parvoviruses for targeting metastases

• Published in: International journal of cancer Vol. 109; no. 5; pp. 742 - 749
• Main Authors: Raykov, Zahari, Balboni, Ginette, Aprahamian, Marc, Rommelaere, Jean
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01-05-2004; Wiley-Liss
• Subjects: Animals; Antibodies, Neoplasm; Antibodies, Viral; Biological and medical sciences; carrier cell; Coculture Techniques; Disease Models, Animal; DNA, Viral; Feasibility Studies; Fluorescent Antibody Technique; hepatoma; Liver Neoplasms, Experimental - pathology; Liver Neoplasms, Experimental - therapy; Lung Neoplasms - secondary; Lung Neoplasms - therapy; Medical sciences; metastases; Microscopy, Fluorescence; oncolysis; Other treatments; Parvovirus; parvovirus H-1; Rats; Treatment. General aspects; Tumors; Parvovirus H1; Delivery system; Lung disease; Parvovirus; Morris hepatoma; Rat; Respiratory disease; Lung; Rodentia; Hepatic disease; Malignant tumor; Metastasis; Oncolytic virus; Virus; Vertebrata; Mammalia; Treatment; Parvoviridae; Animal; Established cell line; Digestive diseases; Carrier; Tumor cell; Parvovirinae
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.20013

Over the last few years, naturally occurring or genetically manipulated oncolytic viruses gained increasing attention as novel therapeutics for cancer treatment. The present work provides proof of principle that an organotropic cell‐based carrier system is suitable to deliver oncolytic parvoviruses to a tissue known to be a target for the formation of metastases. Carrier cells were inactivated by γ‐irradiation after infection, which was found not to affect the production and release of parvoviruses that were capable of lysing cocultured target neoplastic cells. Although systemically administered parvovirus H‐1 showed a pronounced therapeutic effect against the development of established Morris hepatoma (MH3924A) lung metastases, the carrier cell strategy offered a number of advantages. Infected carriers were able to sustain H‐1 virus expression for 6 days in the lungs of rats affected by metastatic disease and to reduce the spreading of the virus to peripheral organs. Compared to direct virus injection, the carrier cell protocol led to an improved therapeutic effect (metastases suppression) and a lesser generation of virus‐neutralizing antibodies. These data support the use of carrier cells to deliver oncolytic viruses and/or viral vectors locally in tumors and, more particularly, metastases. © 2004 Wiley‐Liss, Inc.