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.
Sommermeyer
Daniel
D
Max-Delbrück-Center for Molecular Medicine, Berlin, Germany.
Neudorfer
Julia
J
Weinhold
Monika
M
Leisegang
Matthias
M
Engels
Boris
B
Noessner
Elfriede
E
Heemskerk
Mirjam H M
MH
Charo
Jehad
J
Schendel
Dolores J
DJ
Blankenstein
Thomas
T
Bernhard
Helga
H
Uckert
Wolfgang
W
D000818:Animals; D002460:Cell Line; D018014:Gene Transfer Techniques; D006801:Humans; D051379:Mice; D011948:Receptors, Antigen, T-Cell / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D013601:T-Lymphocytes / Q000737:chemistry / Q000276:immunology*; D023822:Tissue Engineering
D011948:Receptors, Antigen, T-Cell