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Publication : Transfer of TCR genes into mature T cells is accompanied by the maintenance of parental T cell avidity.

First Author  Rubinstein MP Year  2003
Journal  J Immunol Volume  170
Issue  3 Pages  1209-17
PubMed ID  12538678 Mgi Jnum  J:108263
Mgi Id  MGI:3623574 Doi  10.4049/jimmunol.170.3.1209
Citation  Rubinstein MP, et al. (2003) Transfer of TCR genes into mature T cells is accompanied by the maintenance of parental T cell avidity. J Immunol 170(3):1209-17
abstractText  The adoptive transfer of tumor-specific T cells expanded in vitro can be of significant therapeutic value in select cancer patients. This strategy is limited though, as it is often difficult, if not impossible, to obtain T cells of clinical value. The transfer of TCR genes to mature T cells to generate tumor-reactive T cells provides a potential mechanism to overcome these limitations. To evaluate the feasibility of such an approach and the quality of the resulting T cells, we generated replication-deficient retroviral vectors using the well-characterized OT-1 TCR genes. After transducing murine T cells, we were able to expand large numbers of Ag-specific T cells that were functionally active against tumor cells expressing the relevant Ag. Furthermore, we found that T cells expressing retrovirally encoded TCR had avidity that was similar to that of the parental clone. This maintenance of avidity was despite variable expression of the retrovirally encoded TCR and the presence of potentially competing endogenous TCRs. These results suggest that the inherent qualities of the TCR, as dictated by the coding sequence, are the most critical parameters in the generation of high-avidity T cells.
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