Improved Production Strategies for Oncolytic Measles Viruses as a Therapeutic Cancer Treatment

Abstract

Among the variety of currently investigated oncolytic viruses, the excellent safety record, the natural oncotropism, and the possibilities of genetic engineering make the oncolytic Measles virus (oMeV) particularly promising for cancer (immuno-)virotherapy. Clinical trials of oMeV indicate an efficient and well-tolerated treatment. However, high doses (10⁹–10¹¹ TCID₅₀ or more) are needed per patient, turning the manufacturing process into a bottleneck of this therapeutic concept.

In this chapter, we present different strategies for a genetic engineering of oMeV, aiming at both high tumor specificity and therapeutic efficacy. We further address the manufacturing challenges and describe strategies for upstream and downstream processing for oMeV. We describe how the production of oMeV can be improved by distinct modifications of the involved process steps and identify topics that require further investigation. For upstream processing, the selection of the host cell line, culture media, and time of harvest are critical for high yields. The downstream processing consists of several unit operations involving state-of-the-art techniques depth filtration, chromatography, and tangential flow filtration) to concentrate the oMeV and effectively remove impurities. Our identified process conditions ensuring high yields and purity of the final drug product pave the way to manufacture oMeV at cGMP quality for future clinical applications.