Literature Review Of Applications And Processes In iCELLis™ Bioreactor

Adherent cell culture processes utilize substrate surfaces conducive to cell attachment, growth, and proliferation within a controlled, artificial environment. Cell culture in such conditions serves as a valuable platform for the biomanufacturing of viral vectors for therapeutic purposes. Lentiviruses (LV), adenoviruses, and adeno-associated viruses (AAV) stand out as key therapeutic agents employed to deliver genetic materials in cell and gene therapies, typically produced through adherent-based cell culture techniques. While traditional approaches rely on plastic flatware like T-flasks or multi-tray systems, recent years have witnessed a surge in demand for cell and gene therapy products, prompting advancements in production methodologies.

Fixed-bed bioreactors have emerged as efficient tools for viral vector production, yet establishing a new process in these systems presents distinct challenges regarding identifying operating spaces and scaling up processes. Ascertaining optimal cell culture parameters and conditions necessitates rigorous process development efforts. Among the innovations are iCELLis bioreactors, single-use, scalable fixed-bed bioreactors designed for adherent cell culture processes. As of 2023, four of the six approved gene therapy products in the US leverage iCELLis technology, spanning adenovirus, oncolytic virus, and AAV processes.

This review evaluates recent publications on diverse applications of the iCELLis™ bioreactor family, offering insights and guidelines for researchers developing new processes. The first section elucidates the features of the technology. The following describes common process conditions for AAV and LV, the main gene therapy viral vectors, including cell lines, cell density, media composition, feed strategies, transfection methods, and operational parameters. Finally, an overview of the production of oncolytic therapies, vaccines, recombinant proteins, and extracellular vesicles is provided.