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. 2020 Sep 2;11:1568. doi: 10.3389/fimmu.2020.01568

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Copyright © 2020 Jakobsen and Gjerstorff.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Epigenetic pre-treatment sensitizes cancer cells to cancer/testis antigen-directed CAR T-cell therapy. T cells from a patient are harvested through leukapheresis. The T cells are activated and genetically modified to express chimeric antigen receptors (CARs) ex vivo before they are expanded and reinfused into the patient. Pre-treatment of patients with epigenetic drugs, such as DNA methyltransferase (DNMT) inhibitors, increases cancer/testis (CT) antigen and HLA-I expression on cancer cells, leading to enhanced recognition of cancer cells by CAR T cells. Both CAR T cells made from conventional antibodies and TCR mimic antibodies (recognizing antigen peptides presented in complex with HLA-I) are available strategies.