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

Simon B, Wiesinger M, Maerz J, Wistuba-Hamprecht K, Weide B, Schuler-Thurner B, Schuler G, Dörrie J, Uslu U (2018)

Publication Type: Journal article

Publication year: 2018

Journal

Book Volume: 19

Journal Issue: 8

DOI: 10.3390/ijms19082365

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.

Authors with CRIS profile

Involved external institutions

Eberhard Karls Universität Tübingen Germany (DE)

How to cite

APA:

Simon, B., Wiesinger, M., Maerz, J., Wistuba-Hamprecht, K., Weide, B., Schuler-Thurner, B.,... Uslu, U. (2018). The Generation of CAR-Transfected Natural Killer T Cells for the Immunotherapy of Melanoma. International Journal of Molecular Sciences, 19(8). https://dx.doi.org/10.3390/ijms19082365

MLA:

Simon, Bianca, et al. "The Generation of CAR-Transfected Natural Killer T Cells for the Immunotherapy of Melanoma." International Journal of Molecular Sciences 19.8 (2018).

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