Kurzfassung

In a human melanoma model (MA-MEL-86/INTH) T-cell receptor (TCR)-mediated, but HLA-independent recognition of autologous tumor cells by CD8+ T cells has been observed. In particular, these T cells lyse naturally occurring autologous melanoma-cell variants exhibiting total loss of HLA-class I expression. We have identified TRP2 (tyrosinase-related protein 2; syn.: L-dopachrome tautomerase) as one of their target antigens. They recognize intact TRP2 molecules on the cell surface of melanoma...In a human melanoma model (MA-MEL-86/INTH) T-cell receptor (TCR)-mediated, but HLA-independent recognition of autologous tumor cells by CD8+ T cells has been observed. In particular, these T cells lyse naturally occurring autologous melanoma-cell variants exhibiting total loss of HLA-class I expression. We have identified TRP2 (tyrosinase-related protein 2; syn.: L-dopachrome tautomerase) as one of their target antigens. They recognize intact TRP2 molecules on the cell surface of melanoma cells and melanocytes. Directing T cells against naturally occurring HLA-loss variants would safeguard all efforts to generate an efficient and sustained anti-tumor immune response. But imprecisely targeted TCR are known to cause severe and life-threatening off-target effects. Within the project two distinct HLA-independent anti-TRP2 TCR are applied to preclinical mouse experiments to explore the efficacy and safety of their adoptive transfer prior to a clinical application.» weiterlesen» einklappen