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      1. Author :
        Ahmadi, M.; King, J. W.; Xue, S. A.; Voisine, C.; Holler, A.; Wright, G. P.; Waxman, J.; Morris, E.; Stauss, H. J.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Blood
      6. Products :
      7. Volume :
        N/A
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        N/A
      12. Abstract :
        The function of T cell receptor (TCR) gene modified T cells is dependent on efficient surface expression of the introduced TCR alpha/beta heterodimer. We tested whether endogenous CD3 chains are rate-limiting for TCR expression and antigen-specific T cell function. We show that co-transfer of CD3 and TCR genes into primary murine T cells enhanced TCR expression and antigen-specific T cell function in vitro. Peptide titration experiments showed that T cells expressing introduced CD3 and TCR genes recognised lower concentration of antigen than T cells expressing TCR only. In vivo imaging revealed that TCR+CD3 gene modified T cells infiltrated tumors faster and in larger numbers, which resulted in more rapid tumor elimination compared to T cells modified by TCR only. Following tumor clearance, TCR+CD3 engineered T cells persisted in larger numbers than TCR-only T cells and mounted a more effective memory response when re-challenged with antigen. The data demonstrate that provision of additional CD3 molecules is an effective strategy to enhance the avidity, anti-tumor activity and functional memory formation of TCR gene modified T cells in vivo.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21750319
      14. Call Number :
        135769
      15. Serial :
        5654