AUTHOR=Sudarsanam Harish , Buhmann Raymund , Henschler Reinhard TITLE=Influence of Culture Conditions on Ex Vivo Expansion of T Lymphocytes and Their Function for Therapy: Current Insights and Open Questions JOURNAL=Frontiers in Bioengineering and Biotechnology VOLUME=10 YEAR=2022 URL=https://www.frontiersin.org/journals/bioengineering-and-biotechnology/articles/10.3389/fbioe.2022.886637 DOI=10.3389/fbioe.2022.886637 ISSN=2296-4185 ABSTRACT=

Ex vivo expansion of T lymphocytes is a central process in the generation of cellular therapies targeted at tumors and other disease-relevant structures, which currently cannot be reached by established pharmaceuticals. The influence of culture conditions on T cell functions is, however, incompletely understood. In clinical applications of ex vivo expanded T cells, so far, a relatively classical standard cell culture methodology has been established. The expanded cells have been characterized in both preclinical models and clinical studies mainly using a therapeutic endpoint, for example antitumor response and cytotoxic function against cellular targets, whereas the influence of manipulations of T cells ex vivo including transduction and culture expansion has been studied to a much lesser detail, or in many contexts remains unknown. This includes the circulation behavior of expanded T cells after intravenous application, their intracellular metabolism and signal transduction, and their cytoskeletal (re)organization or their adhesion, migration, and subsequent intra-tissue differentiation. This review aims to provide an overview of established T cell expansion methodologies and address unanswered questions relating in vivo interaction of ex vivo expanded T cells for cellular therapy.