The Generation of CAR-Transfected Natural Killer T Cells for the Immunotherapy of Melanoma

International Journal of Molecular Sciences

卷:19

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