The success of adoptive cellular therapy depends on the ability to select optimally or produce cells genetically with the desired antigenic specificity, and then induce cellular proliferation while preserving the effector function, engraftment, and homing abilities of the lymphocytes. Unfortunately, many previous clinical trials were carried out with adoptively transferred cells that were propagated in what are now understood to be sub-optimal conditions that impair the essential functions of the adoptively transferred cells. This article reviews some of the lessons and developments emerging from the past 20 years of adoptive immunotherapy trials and basic immunology regarding immunogenicity, T cell homeostasis, and the maintenance of tolerance and repertoire.
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