Research progress and therapeutic design of TCR/CAR modified T cells in tumor immunotherapy

LU Wenbin; GONG Xuechao; JIN Jianhua; HU Wenwei

doi:10.13431/j.cnki.immunol.j.20180025

Abstract：Adoptive T-cell therapies have shown exceptional promise in the treatment of cancer,especially B-cell malignancies.Two distinct strategies have been used to redirect the activity of ex vivo engineered T cells.In one case,synthetic constructs called chimeric antigen receptors (CARs) that contain antibody fragments (scFv variable region),transmembrane domain linking to the hinger/spacer and signaling multiple components have been introduced into T cells.In the other strategy,the well-known ability of the T-cell receptor (TCR) to recognize a specific peptide bound to major histocompatibility complex molecule has been exploited by introducing a TCR against a cancer-associated peptide/human leukocyte antigen complex (MHC).Whereas many papers have described these two approaches,this review focuses on a few recent advances of significant interest.The early success of CARs has been followed by questions about optimal configurations of these synthetic constructs,especially for efficacy against solid tumors.Among the many features that are important,the dimensions and stoichiometries of CAR/ antigen complexes at the synapse have recently begun to be appreciated.In TCR-mediated approaches,recent evidence that mutated peptides (neoantigens) serve as targets for T-cell responses suggests that these neoantigens may also provide new opportunities for adoptive T-cell therapies with TCRs.