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| Item Type: | Article |
|---|---|
| Title: | Enhanced functionality of T cell receptor-redirected T cells is defined by the transgene cassette |
| Creators Name: | Leisegang, M., Engels, B., Meyerhuber, P., Kieback, E., Sommermeyer, D., Xue, S.A., Reuß, S., Stauss, H. and Uckert, W. |
| Abstract: | The transfer of T cell receptor (TCR) genes allows to endow T cells with a new antigen specificity. For clinical applications of TCR-redirected T cells, efficient functional expression of the transgenic TCR is a key prerequisite. Here, we compared the influence of the transgene cassette on the expression and function of the murine TCR P14 (recognizing a LCMV gp33 epitope) and the human TCR WT-1 (recognizing an epitope of the tumor-associated antigen WT-1). We constructed different vectors, in which TCRalpha- and beta-chain genes were either (a) linked by an internal ribosomal entry site (IRES), (b) combined by a 2A peptide, or (c) introduced into two individual retroviral constructs. While in a TCR-deficient T cell line TCR P14 was expressed equally well by all constructs, we found that IRES- but not 2A-employing TCR expression is hampered in a TCR-bearing cell line and in primary murine T cells where the transgenic TCR has to compete with endogenous TCR chains. Similarly, 2A-linked TCR WT-1 genes yielded highest expression and function as measured by tetramer binding and peptide-specific IFN-gamma secretion. Differences in expression were independent of copy number integration as shown by real-time PCR. Thus, linking TCRalpha- and beta-chain genes by a 2A peptide is superior to an IRES for TCR expression and T cell function. |
| Keywords: | T Cell Avidity, T Cell Receptor, Retroviral Vector, IRES, 2A Peptide, Animals, Mice |
| Source: | Journal of Molecular Medicine |
| ISSN: | 0946-2716 |
| Publisher: | Springer |
| Volume: | 86 |
| Number: | 5 |
| Page Range: | 573-583 |
| Date: | May 2008 |
| Additional Information: | The original publication is available at www.springerlink.com |
| Official Publication: | https://doi.org/10.1007/s00109-008-0317-3 |
| PubMed: | View item in PubMed |
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