Gestern in Nature veröffentlicht:
https://www.nature.com/articles/s41590-019-0578-8
Abstract
Human leukocyte antigen (HLA)-independent, T cell–mediated targeting of cancer cells would allow immune destruction of malignancies in all individuals. Here, we use genome-wide CRISPR–Cas9 screening to establish that a T cell receptor (TCR) recognized and killed most human cancer types via the monomorphic MHC class I-related protein, MR1, while remaining inert to noncancerous cells. Unlike mucosal-associated invariant T cells, recognition of target cells by the TCR was independent of bacterial loading. Furthermore, concentration-dependent addition of vitamin B-related metabolite ligands of MR1 reduced TCR recognition of cancer cells, suggesting that recognition occurred via sensing of the cancer metabolome. An MR1-restricted T cell clone mediated in vivo regression of leukemia and conferred enhanced survival of NSG mice. TCR transfer to T cells of patients enabled killing of autologous and nonautologous melanoma. These findings offer opportunities for HLA-independent, pan-cancer, pan-population immunotherapies.Das wäre, wenn es sich bestätigen sollte, in der Tat ein Meilenstein in der Krebstherapie. T-Cell Therapien sind gut etabliert, mit dem neuen Rezeptor hätte man dann die Möglichkeit fast jeden Tumor zu bekämpfen. One fits all!MR1 is an attractive target for cancer immunotherapy due to its monomorphic, ubiquitously expressed nature. Recent advances
in MR1 tetramers and ligand discoveries have progressed knowl- edge in this area, but there is still much to be discovered. Here, we confirmed cancer cell recognition by a T cell clone that responded to multiple cancer cell lines from diverse tissue types, resulting in killing of cancer cells in vitro and in vivo.