International Journal of Molecular Sciences | 卷:19 |
The Generation of CAR-Transfected Natural Killer T Cells for the Immunotherapy of Melanoma | |
Benjamin Weide1  Kilian Wistuba-Hamprecht1  Bianca Simon2  Beatrice Schuler-Thurner2  Gerold Schuler2  Ugur Uslu2  Johannes März2  Manuel Wiesinger2  Jan Dörrie2  | |
[1] Eberhard-Karls-Universität Tübingen, University Medical Center, Department of Dermatology, 72076 Tübingen, Germany; | |
[2] Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Department of Dermatology, Universitätsklinikum Erlangen, 91054 Erlangen, Germany; | |
关键词: cancer; human; adoptive T-cell therapy; chimeric antigen receptor; T-cell receptor; immune escape; T cells; NKT cells; | |
DOI : 10.3390/ijms19082365 | |
来源: DOAJ |
【 摘 要 】
Natural killer T (NKT) cells represent a cell subpopulation that combines characteristics of natural killer (NK) cells and T cells. Through their endogenous T-cell receptors (TCRs), they reveal a pronounced intrinsic anti-tumor activity. Thus, a NKT cell transfected with a chimeric antigen receptor (CAR), which recognizes a tumor-specific surface antigen, could attack tumor cells antigen-specifically via the CAR and additionally through its endogenous TCR. NKT cells were isolated from peripheral blood mononuclear cells (PBMCs), expanded, and electroporated with mRNA encoding a chondroitin sulfate proteoglycan 4 (CSPG4)-specific CAR. The CAR expression on NKT cells and their in vitro functionality were analyzed. A transfection efficiency of more than 80% was achieved. Upon stimulation with melanoma cells, CAR-NKT cells produced cytokines antigen-specifically. Compared with conventional CAR-T cells, cytokine secretion of CAR-NKT cells was generally lower. Specific cytotoxicity, however, was similar with CAR-NKT cells showing a trend towards improved cytotoxicity. Additionally, CAR-NKT cells could kill target cells through their endogenous TCRs. In summary, it is feasible to generate CAR-NKT cells by using mRNA electroporation. Their CAR-mediated cytotoxicity is at least equal to that of conventional CAR-T cells, while their intrinsic cytotoxic activity is maintained. Thus, CAR-NKT cells may represent a valuable alternative to conventional CAR-T cells for cancer immunotherapy.
【 授权许可】
Unknown