Description:
Ex vivo expansion of T lymphocytes is a central process in the generation of cellular therapiestargeted at tumors and other disease-relevant structures,which currently cannot be reached byestablished 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 relativelyclassical standard cell culture methodology has been established. The expanded cells havebeen characterized in both preclinical models and clinical studies mainly using a therapeuticendpoint, for example antitumor response and cytotoxic function against cellular targets,whereas the influence of manipulations of T cells ex vivo including transduction and cultureexpansion 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, theirintracellular metabolism and signal transduction, and their cytoskeletal (re)organization or theiradhesion, migration, and subsequent intra-tissue differentiation. This review aims to provide anoverview of established T cell expansion methodologies and address unanswered questionsrelating in vivo interaction of ex vivo expanded T cells for cellular therapy.