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Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
Published on: January 7, 2019
Reovirus-based therapy for cancer
Kevin Kelly1, Steffan Nawrocki, Alain Mita
1University of Texas Health Science Center, Institute for Drug Development, Cancer Therapy and Research Center, 7979 Wurzbach Road, San Antonio, Texas 78229, USA.
Abstract:
Reovirus is an oncolytic virus that is not associated with significant disease in humans, but is selectively able to replicate in cancer cells through exploitation of abnormal Ras signaling. Pre-clinical studies have demonstrated that treatment with reovirus is associated with significant anticancer activity across a range of tumor types. Reolysin is a proprietary formulation of the human reovirus developed by Oncolytics Biotech. Clinical evaluation of reovirus therapy has shown that it is well tolerated when administered locally or systemically. Encouraging anticancer efficacy has been observed with single-agent treatment and in combination with chemotherapy and radiotherapy. Phase II studies are currently evaluating reovirus alone and in combination with standard therapy in an array of tumor types. While immune sensitization hinders the anticancer efficacy of reovirus, it is important in preventing systemic toxicity. Immunosuppressive strategies are being developed that reduce immune neutralization of the virus to allow for improved tumor penetration, but retain sufficient antibody levels to protect normal tissues. The lack of toxicity and promising efficacy of reovirus has raised hopes that it will become an established anticancer agent.
Insights
Reovirus, an oncolytic virus, shows promise in cancer treatment by selectively targeting cancer cells. Clinical studies indicate good tolerability and encouraging anticancer activity, even in combination therapies.
Area of Science:
- Oncology
- Virology
- Immunology
Background:
- Reovirus is an oncolytic virus with a natural tropism for cancer cells, exploiting aberrant Ras signaling pathways.
- Pre-clinical research indicates significant anticancer activity of reovirus across various tumor types.
- Reolysin is a specific formulation of human reovirus being developed for therapeutic applications.
Purpose of the Study:
- To evaluate the safety and efficacy of reovirus (Reolysin) as an oncolytic cancer therapy.
- To explore the potential of reovirus in combination with standard cancer treatments.
- To investigate strategies for optimizing reovirus delivery and efficacy by modulating the immune response.
Main Methods:
- Clinical evaluation of reovirus therapy, including local and systemic administration.
- Assessment of reovirus efficacy as a single agent and in combination with chemotherapy and radiotherapy.
- Development of immunosuppressive strategies to enhance tumor penetration while maintaining safety.
Main Results:
- Reovirus therapy has demonstrated good tolerability in clinical trials.
- Encouraging anticancer efficacy has been observed with reovirus, both alone and in combination regimens.
- Phase II studies are ongoing to further assess reovirus in diverse cancer types.
Conclusions:
- Reovirus therapy presents a promising, well-tolerated approach to cancer treatment.
- Further research and development, including immune modulation strategies, may enhance reovirus's role in oncology.
- Reovirus holds potential to become an established anticancer agent due to its favorable safety and efficacy profile.
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