Selective Expansion of Genetically Modified T Cells Using a Chimeric IL-2 Receptor for Cancer Therapy

摘要

T cells have been used for cancer immunotherapy because they play a central role in the cellular immunity. One approach to cure cancers is that tumor-specific T cells are activated in vitro and subsequently injected into patients. However, desired therapeutic effect has not been attained due to difficulty to maintain activated T cells for a prolonged period after injection. To solve this problem, we thought to use an interleukin (IL)-2-dependent growth signal in T cells for maintenance of activated Tcells. If non-toxic molecules can substitute for the function of IL-2, genetically modified T cells can be expanded selectively without IL-2 and no side effect would occur. In this study, we replaced IL-2 binding domains of IL-2 receptor (IL-2R) (3 andy chains by antibody variable regions recognizing a cognate antigen. Because these chimeric IL-2Rs could replace an IL-2-mediated signal by an antigen-mediated one, only the T cells with these chimeric receptors would grow in the presence of the cognateantigen but without IL-2.