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Int. J. Mol. Sci. 2018, 19(8), 2365; https://doi.org/10.3390/ijms19082365

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

1
Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Department of Dermatology, Universitätsklinikum Erlangen, 91054 Erlangen, Germany
2
Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Division of Genetics, Department of Biology, 91058 Erlangen, Germany
3
Eberhard-Karls-Universität Tübingen, University Medical Center, Department of Dermatology, 72076 Tübingen, Germany
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 13 July 2018 / Revised: 5 August 2018 / Accepted: 9 August 2018 / Published: 11 August 2018
(This article belongs to the Special Issue Cancer Immunology and Immunotherapy)
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Abstract

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. View Full-Text
Keywords: cancer; human; adoptive T-cell therapy; chimeric antigen receptor; T-cell receptor; immune escape; T cells; NKT cells cancer; human; adoptive T-cell therapy; chimeric antigen receptor; T-cell receptor; immune escape; T cells; NKT cells
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Simon, B.; Wiesinger, M.; März, J.; Wistuba-Hamprecht, K.; Weide, B.; Schuler-Thurner, B.; Schuler, G.; Dörrie, J.; Uslu, U. The Generation of CAR-Transfected Natural Killer T Cells for the Immunotherapy of Melanoma. Int. J. Mol. Sci. 2018, 19, 2365.

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