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However, relapse of the tumor can occur due to immune\u2010escape mechanisms developed by the tumor cells, for example antigen loss, downregulation of the major histocompatibility complex presentation machinery and defects in antigen processing. To counteract these mechanisms, we combined a T\u2010cell receptor and a chimeric antigen receptor, specific for different common melanoma antigens, gp100 (<jats:styled-content style=\"fixed-case\">PMEL<\/jats:styled-content>) and <jats:styled-content style=\"fixed-case\">MCSP<\/jats:styled-content> (<jats:styled-content style=\"fixed-case\">HMW<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">MAA<\/jats:styled-content>), to generate functional <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>8<jats:sup>+<\/jats:sup> T cells expressing two additional receptors (<jats:styled-content style=\"fixed-case\">TETAR<\/jats:styled-content>s) by electroporation of receptor\u2010encoding <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content>. These <jats:styled-content style=\"fixed-case\">TETAR<\/jats:styled-content>s produced cytokines and were lytic upon recognition of each of their cognate antigens, while no reciprocal inhibition of the receptors occurred. When stimulated with target cells, which express both antigens, an enhanced effect was suggested. The confirmation that chimeric antigen receptors and T\u2010cell receptors can be functionally combined opens up new avenues in cancer immunotherapy, and the generation of <jats:styled-content style=\"fixed-case\">TETAR<\/jats:styled-content>s helps by\u2010passing major mechanisms by which tumor cells escape immune recognition.<\/jats:p>","DOI":"10.1111\/exd.13095","type":"journal-article","created":{"date-parts":[[2016,6,1]],"date-time":"2016-06-01T07:57:18Z","timestamp":1464767838000},"page":"872-879","source":"Crossref","is-referenced-by-count":35,"title":["Combining a chimeric antigen receptor and a conventional T\u2010cell receptor to generate T cells expressing two additional receptors (<scp>TETAR<\/scp>s) for a multi\u2010hit immunotherapy of melanoma"],"prefix":"10.1111","volume":"25","author":[{"given":"Ugur","family":"Uslu","sequence":"first","affiliation":[{"name":"Department of Dermatology Universit\u00e4tsklinikum Erlangen  Erlangen 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