European Journal of Immunology 36 (11): 3052-3059 (2006-11)

Sommermeyer D.; Neudorfer J.; Weinhold M.; Leisegang M.; Engels B.; Noessner E.; Heemskerk M.H.; Charo J.; Schendel D.J.; Blankenstein T.; Bernhard H.; Uckert W.

Designer T cells by T cell receptor replacement

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 TCRalpha/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.

Keywords: Animals, TCR Replacement, T cells, Mice, TCR, Gene Therapy

Type: Article

PubMed: 17051621
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