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Opportunities to debottleneck the downstream processing of the oncolytic measles virus
Daniel Loewe1,2, Hauke Dieken1, Tanja A Grein1
1Institute of Bioprocess Engineering and Pharmaceutical Technology, University of Applied Sciences Mittelhessen, Giessen, Germany.
Abstract:
Oncolytic viruses (including measles virus) offer an alternative approach to reduce the high mortality rate of late-stage cancer. Several measles virus strains infect and lyse cancer cells efficiently, but the broad application of this therapeutic concept is hindered by the large number of infectious particles required (108-1012 TCID50 per dose). The manufacturing process must, therefore, achieve high titers of oncolytic measles virus (OMV) during upstream production and ensure that the virus product is not damaged during purification by applying appropriate downstream processing (DSP) unit operations. DSP is currently a production bottleneck because there are no specific platforms for OMV. Infectious OMV must be recovered as intact, enveloped particles, and host cell proteins and DNA must be reduced to acceptable levels to meet regulatory guidelines that were developed for virus-based vaccines and gene therapy vectors. Handling such high viral titers and process volumes is technologically challenging and expensive. This review considers the state of the art in OMV purification and looks at promising DSP technologies. We discuss here the purification of other enveloped viruses where such technologies could also be applied to OMV. The development of DSP technologies tailored for enveloped viruses is necessary to produce sufficient titers for virotherapy, which could offer hope to millions of patients suffering from incurable cancer.
Insights
Manufacturing challenges limit oncolytic measles virus (OMV) cancer therapy. Developing specific downstream processing (DSP) technologies is crucial for producing sufficient OMV titers for effective virotherapy.
Area of Science:
- Virology
- Oncology
- Biotechnology
Background:
- Oncolytic viruses, like measles virus, show promise for treating late-stage cancers.
- High doses (10^8-10^12 TCID50) of oncolytic measles virus (OMV) are needed, posing manufacturing challenges.
- Current downstream processing (DSP) is a bottleneck for producing sufficient OMV titers.
Purpose of the Study:
- To review the current state of OMV purification.
- To identify promising DSP technologies for OMV production.
- To highlight the need for DSP platforms tailored for enveloped viruses.
Main Methods:
- Review of existing literature on OMV purification.
- Analysis of DSP technologies used for other enveloped viruses.
- Discussion of challenges in handling high viral titers and volumes.
Main Results:
- No specific DSP platforms currently exist for OMV.
- Existing DSP methods face challenges in recovering intact OMV and reducing contaminants.
- Technologies used for other enveloped viruses may be adaptable for OMV.
Conclusions:
- Development of tailored DSP technologies is essential for OMV production.
- Advances in DSP are necessary to enable virotherapy for millions of cancer patients.
- Overcoming DSP bottlenecks could unlock the therapeutic potential of OMV.
