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Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
Published on: January 7, 2019
Carrier cell-mediated delivery of oncolytic parvoviruses for targeting metastases
Zahari Raykov1, Ginette Balboni, Marc Aprahamian
1Infection and Cancer Program, ATV-Abteilung F0100/INSERM U375, Deutsches Krebsforschungszentrum, Postfach 101949, D-69009 Heidelberg, Germany.
Abstract:
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 gamma-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.
Insights
Cell-based carriers effectively deliver oncolytic parvoviruses to treat cancer metastases. This approach enhances therapeutic effects and reduces virus spread compared to direct injection.
Area of Science:
- Oncolytic virotherapy
- Cancer research
- Virology
Background:
- Oncolytic viruses are emerging as promising cancer therapeutics.
- Targeting solid tumors and metastases with oncolytic viruses remains challenging.
- Developing effective delivery systems is crucial for oncolytic virus efficacy.
Purpose of the Study:
- To evaluate a cell-based carrier system for delivering oncolytic parvoviruses.
- To assess the efficacy of this system in treating lung metastases.
- To compare the carrier system with direct virus administration.
Main Methods:
- Organotropic cell-based carriers infected with parvovirus H-1.
- Carrier cells inactivated by gamma-irradiation.
- Administration of infected carriers to rats with Morris hepatoma lung metastases.
- Assessment of virus expression, therapeutic effect, and antibody generation.
Main Results:
- Inactivated carrier cells sustained oncolytic parvovirus expression in lung metastases for 6 days.
- The carrier cell system demonstrated improved therapeutic efficacy in suppressing metastases.
- Reduced virus spread to peripheral organs and lower generation of virus-neutralizing antibodies were observed.
- Parvoviruses released from carriers effectively lysed cocultured neoplastic cells.
Conclusions:
- Cell-based carrier systems are suitable for delivering oncolytic parvoviruses to target tissues, particularly metastases.
- This strategy offers advantages over direct virus injection, including enhanced therapeutic effects and reduced immunogenicity.
- The findings support the use of carrier cells for localized delivery of oncolytic viruses in cancer treatment.
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