AUTHOR=Gatla Himavanth , Uth Nicholas , Levinson Yonatan , Navaei Ali , Sargent Alex , Ramaswamy Senthil , Friedrich Ben-Nun Inbar TITLE=Enabling Allogeneic T Cell-Based Therapies: Scalable Stirred-Tank Bioreactor Mediated Manufacturing JOURNAL=Frontiers in Medical Technology VOLUME=4 YEAR=2022 URL=https://www.frontiersin.org/journals/medical-technology/articles/10.3389/fmedt.2022.850565 DOI=10.3389/fmedt.2022.850565 ISSN=2673-3129 ABSTRACT=

Allogeneic T cells are key immune therapeutic cells to fight cancer and other clinical indications. High T cell dose per patient and increasing patient numbers result in clinical demand for a large number of allogeneic T cells. This necessitates a manufacturing platform that can be scaled up while retaining cell quality. Here we present a closed and scalable platform for T cell manufacturing to meet clinical demand. Upstream manufacturing steps of T cell activation and expansion are done in-vessel, in a stirred-tank bioreactor. T cell selection, which is necessary for CAR-T-based therapy, is done in the bioreactor itself, thus maintaining optimal culture conditions through the selection step. Platform's attributes of automation and performing the steps of T cell activation, expansion, and selection in-vessel, greatly contribute to enhancing process control, cell quality, and to the reduction of manual labor and contamination risk. In addition, the viability of integrating a closed, automated, downstream process of cell concentration, is demonstrated. The presented T cell manufacturing platform has scale-up capabilities while preserving key factors of cell quality and process control.