Optimizing TCR gene transfer.

摘要

Adoptive transfer of antigen-specific T cells is an attractive strategy to provide cancer patients with immune cells of a desired specificity and the efficacy of such adoptive transfers has been demonstrated in several clinical studies [1-3]. Because the T cell specificity is exclusively determined by the T cell receptor [TCR], transfer of TCR genes into recipient Tcells may be used as an alternative approach for the transfer of tumor specific T cell immunity. TCR-transferred T cells have been demonstrated to be functionally active in vitro as well as in mouse model systems [4-10]. TCR-transferred T cells exert cytolytic activity, show antigen specific proliferation and secrete additional cyto-kines. In vivo, these redirected T cells are able to expand and home to the relevant affected tissues. TCR gene therapy may therefore be an alternative method to provide Large numbers of specific immune cells circumventing the laborious and time-consuming tissue culture procedures needed for the in vitro generation of specific T cell responses. In addition, TCR transfer allows the use of effective antigen specific TCRs in Large patient groups.