Establishing Suspension Cell Cultures for Improved Manufacturing of Oncolytic Adenovirus

Abstract

Recent clinical trials have shown the potential of oncolytic adenoviruses as a cancer immunotherapy. A successful transition of oncolytic adenovirus to clinical applications requires efficient and good manufacturing practice compatible production and purification bioprocesses. Suspension cultures are preferable for virus production as they can reduce process costs and increase product quality and consistency. This work describes the adaptation of the A549 cell line to suspension culture in serum-reduced medium validated by oncolytic adenovirus production in stirred tank bioreactor. Cell concentrations up to 3 × 106 cells mL−1 are obtained during the production process. At harvest 1.4 × 1010 infectious particles mL−1 and 6.9 ± 1.1 × 1010 viral genome mL−1 are obtained corresponding to a viral genome: infectious particles ratio of 5.2 (± 1.9): 1 confirming the virus quality. Overall, the suspension characteristics of these A549 cells support an easily scalable, less time-consuming, and more cost-effective process for expanded success in the use of oncolytic viruses for cancer therapy.