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Updated: Jul 11, 2026
Ex Vivo Infection of Live Tissue with Oncolytic Viruses
Published on: June 25, 2011
Intracellular delivery of oncolytic viruses with engineered Salmonella causes viral replication and cell death
Shradha Khanduja1, Shoshana M K Bloom1, Vishnu Raman1
1Department of Chemical Engineering, University of Massachusetts, Amherst, Amherst, MA, USA.
Abstract:
As therapies, oncolytic viruses regress tumors and have the potential to induce antitumor immune responses that clear hard-to-treat and late-stage cancers. Despite this promise, clearance from the blood prevents treatment of internal solid tumors. To address this issue, we developed virus-delivering Salmonella (VDS) to carry oncolytic viruses into cancer cells. The VDS strain contains the PsseJ-lysE delivery circuit and has deletions in four homologous recombination genes (ΔrecB, ΔsbcB, ΔsbcCD, and ΔrecF) to preserve essential hairpins in the viral genome required for replication and infectivity. VDS delivered the genome for minute virus of mice (MVMp) to multiple cancers, including breast, pancreatic, and osteosarcoma. Viral delivery produced functional viral particles that are cytotoxic and infective to neighboring cells. The release of mature virions initiated new rounds of infection and amplified the infection. Using Salmonella for delivery will circumvent the limitations of oncolytic viruses and will provide a new therapy for many cancers.
Insights
This study introduces virus-delivering Salmonella (VDS) to overcome oncolytic virus limitations. VDS effectively delivers oncolytic viruses to internal tumors, offering a promising new cancer therapy.
Area of Science:
- Oncology
- Virology
- Microbiology
Background:
- Oncolytic viruses show promise for cancer treatment by regressing tumors and stimulating antitumor immunity.
- Systemic administration of oncolytic viruses is limited by rapid clearance from the bloodstream, hindering treatment of internal solid tumors.
Purpose of the Study:
- To develop a novel delivery system for oncolytic viruses to effectively target internal solid tumors.
- To engineer a Salmonella strain capable of delivering oncolytic virus genomes into cancer cells.
Main Methods:
- Developed a modified Salmonella strain (VDS) with a specific delivery circuit (PsseJ-lysE) and deletions in homologous recombination genes (ΔrecB, ΔsbcB, ΔsbcCD, ΔrecF).
- Utilized VDS to deliver the minute virus of mice (MVMp) genome to various cancer models, including breast, pancreatic, and osteosarcoma.
- Assessed the production of functional, infectious, and cytotoxic viral particles post-delivery.
Main Results:
- VDS successfully delivered the MVMp genome to multiple internal cancer types.
- Delivered viral genomes replicated to produce functional viral particles within cancer cells.
- These viral particles were cytotoxic and initiated secondary infections in neighboring cancer cells, amplifying the therapeutic effect.
Conclusions:
- Virus-delivering Salmonella (VDS) circumvents the limitations of traditional oncolytic virus therapy.
- This approach provides a viable strategy for treating internal solid tumors and offers a new therapeutic avenue for various cancers.
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