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Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
Published on: January 7, 2019
Clinical trials involving the oncolytic virus, reovirus: ready for prime time?
Allison J Black1, Don G Morris
1Department of Oncology and Medicine, University of Calgary, 1331 29th St NW, Calgary, AB T2N 4N2, Canada.
Abstract:
The use of oncolytic viruses as a potential cancer therapeutic has been studied extensively over the past 15 years and is now in Phase III human clinical testing. One of the most promising of the viruses is the nonattenuated reovirus type-3 Dearing (RT3D; Reolysin(®), Oncolytics Biotech Inc., AB, Canada). The virus is a laboratory strain of a ubiquitous common environmental virus commonly infecting the respiratory and GI tracts of humans without major sequelae. The Phase I/II clinical trial conducted by Karapanagiotou et al. involved dose escalation of Reolysin to 3 × 10(10) tissue culture infectious dose 50 (TCID(50)) daily for 5 days in combination with paclitaxel (175 mg/m(2)) and carboplatin (area under the curve 5) given on day 1 every 3 weeks. Maximum tolerated dose was not reached in the dose-escalation phase and was only limited by manufacturing concentration limitation. Efficacy was suggested in this heavily pretreated head and neck cancer predominate patient population with a 26.9% response rate (seven out of 26 evaluable patients) of the 34 patients intended to treat. Although this was not a randomized trial, the fact that many of the patients (83%) had already received a platinum agent and subsequently progressed and then responded is of interest.
Insights
Reolysin (Reovirus type-3 Dearing) shows promise as an oncolytic virus therapy for head and neck cancers. A Phase I/II trial indicated a 26.9% response rate in heavily pretreated patients.
Area of Science:
- Oncology
- Virology
- Cancer Therapeutics
Background:
- Oncolytic viruses are extensively studied cancer therapeutics, with Reovirus type-3 Dearing (RT3D) showing significant promise.
- RT3D is a non-pathogenic, ubiquitous virus that infects humans without severe sequelae.
Purpose of the Study:
- To evaluate the safety and efficacy of Reolysin (RT3D) in combination with paclitaxel and carboplatin in patients with advanced head and neck cancers.
- To determine the maximum tolerated dose (MTD) of Reolysin in this patient population.
Main Methods:
- A Phase I/II dose-escalation trial was conducted, administering Reolysin daily for 5 days in combination with paclitaxel and carboplatin every 3 weeks.
- The study involved 34 patients with heavily pretreated head and neck cancers, with 26 evaluable for response.
Main Results:
- The MTD was not reached, with dose limitation due to manufacturing concentration.
- A 26.9% overall response rate was observed in the evaluable patient population.
- Notably, 83% of patients had previously progressed on platinum-based chemotherapy, suggesting potential efficacy in resistant cases.
Conclusions:
- Reolysin in combination with paclitaxel and carboplatin demonstrates a promising response rate in heavily pretreated head and neck cancer patients.
- Further investigation, including randomized trials, is warranted to confirm the efficacy of this oncolytic virus therapy.
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