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Author Spotlight: Addressing Regulatory Gaps in Molecular Studies by Quantifying Viral Vectors in Complex Matrices
Published on: July 14, 2023
Oncolytic Viruses: An Inventory of Shedding Data from Clinical Trials and Elements for the Environmental Risk
Sheela Onnockx1, Aline Baldo1, Katia Pauwels1
1Sciensano, Service Biosafety and Biotechnology, Rue Juliette Wytsmanstraat 14, B-1050 Brussels, Belgium.
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.
Insights
Oncolytic viruses (OV) show promise for cancer therapy but require environmental risk assessment. This review analyzes OV shedding data, crucial for evaluating transmission risk and informing future study designs.
Area of Science:
- Oncology
- Virology
- Regulatory Science
- Environmental Risk Assessment
Background:
- Attenuated and/or genetically modified oncolytic viruses (OV) are emerging as a significant cancer therapy modality.
- The use of genetically modified viruses necessitates adherence to EU regulatory frameworks, including environmental risk assessment (ERA).
- Evaluating potential exposure of non-trial individuals and the environment to OV is a critical component of ERA.
Purpose of the Study:
- To present the most comprehensive and current review of oncolytic virus shedding data from clinical applications.
- To highlight the importance of shedding data in assessing the transmission potential of OV, especially replication-competent ones.
- To provide guidance for designing robust shedding studies, referencing existing European and international guidelines.
Main Methods:
- Systematic review and synthesis of published clinical shedding data for oncolytic viruses.
- Analysis of shedding data in the context of environmental risk assessment requirements.
- Comparison of shedding characteristics between conditionally replicating OV and replication-defective viral vectors.
Main Results:
- The review consolidates existing oncolytic virus shedding data, identifying gaps and inconsistencies in collection methodologies.
- Shedding data is confirmed as a pivotal factor in determining the environmental transmission risk of oncolytic viruses.
- A need for standardized and improved methods for collecting shedding data is evident.
Conclusions:
- This review underscores the critical role of shedding data in the regulatory approval and safe clinical use of oncolytic viruses.
- The findings emphasize the necessity for enhanced shedding study designs to accurately assess environmental exposure and transmission risks.
- The article serves as a resource to aid in the development of future oncolytic virus shedding studies, aligning with regulatory expectations.
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