Oncolytic Viruses: An Inventory of Shedding Data from Clinical Trials and Elements for the Environmental Risk Assessment

Abstract

Attenuated and/or genetically modified oncolytic viruses (OV) gain increasing interest as a promising approach for cancer therapy. Beside the assessment of subject safety, quality and efficacy aspects of medicinal products for human use, genetically modified viruses are also governed by EU regulatory frameworks requiring an environmental risk assessment (ERA). An important element to be assessed as part of the ERA is the incidence of exposure to OV of individuals, other than the trial subjects, and the environment. The evidence-based evaluation of shedding data is considered to be decisive in that context, as it may impact the OV capacity to be transmitted. This is particularly true for OV still able to (conditionally) replicate as opposed to replication-defective viral vectors commonly used in gene therapy or vaccination. To our knowledge, this article presents the most extensive and up-to-date review of shedding data reported with OV employed in clinics. Besides the identification of a topical need for improving the collection of shedding data, this article aims at providing an aid to the design of an appropriate shedding study, thereby relying on and further complementing principles described in existing guidelines issued by European and international institutions.

New hopes for the breast cancer treatment: perspectives on the oncolytic virus therapy

“…Additionally, the objective response rate for radiotherapy was 72.4%, suggesting that Oncorine may increase the radiotherapy sensitivity ( 64 ). Side effects were similar to those that were previously reported, such as pyrexia, nausea, vomiting, fatigue, and pain with sometimes bleeding in the place of injection ( 60 ). There was one case reported of severe side effects - a rectovaginal fistula after Oncorine combined brachytherapy ( 60 ).…”

“…Side effects were similar to those that were previously reported, such as pyrexia, nausea, vomiting, fatigue, and pain with sometimes bleeding in the place of injection ( 60 ). There was one case reported of severe side effects - a rectovaginal fistula after Oncorine combined brachytherapy ( 60 ). Oncorine’s potential in the treatment of liver cancer, MPE, and pancreatic cancer is currently being investigated.…”

“…Additionally, previous clinical trials reported side effects that were mild, completely reversible, and not causing an interruption in treatment, such as subfebrile temperature, pain in the location of the tumour, fatigue, sleepiness, and dyspepsia ( 55 ). Despite its registration in Latvia, Georgia, and Armenia, Rigvir was discontinued in mid-2019 due to manufacturing issues and then suspended for marketing authorization ( 60 ). Currently, there is a new product on the market - Imlygic registered by FDA in 2015 for advanced melanoma ( 7 ).…”