Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 36, Issue 11, Pages 3052-3059Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/eji.200636539
Keywords
gene therapy; T cells; TCR; TCR replacement
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T cell receptor (TCR) gene transfer is a convenient method to produce antigen-specific T cells for adoptive therapy. However, the expression of two TCR in T cells could impair their function or cause unwanted effects by mixed TCR heterodimers. With five different TCR and four different T cells, either mouse or human, we show that some TCR are strong - in terms of cell surface expression - and replace weak TCR on the cell surface, resulting in exchange of antigen specificity. Two strong TCR are co-expressed. A mouse TCR replaces human TCR on human T cells. Even though it is still poorly understood why some TCR alpha/beta combinations are preferentially expressed on T cells, our data suggest that, in the future, designer T cells with exclusive tumor reactivity can be generated by T cell engineering.
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