Immunotherapy is attracting attention as the fourth cancer treatment method following surgery, radiation therapy, and chemotherapy.In immunotherapy, killer T cells that attack cancer cells are required, but it is difficult to obtain a large number of killer T cells, and the problem is that they become exhausted as the attack continues.

　Therefore, a method was developed to generate iPS cells from exhausted killer T cells and differentiate them into new killer T cells.Previous studies have suggested that in order to induce higher quality killer T cells, it is necessary to go through progenitor cells called DP thymocytes, so this method was first examined in this study.

　The results showed that at the DP thymocyte stage, extra T cell receptor (TCR) remodeling occurred, reducing the ability to identify antigens.Therefore, when genes involved in TCR reconstruction were excluded by genome editing, we were able to produce killer T cells that maintain antigen specificity and effectively attack cancer cells.
　Subsequently, studies were conducted using a method using allogeneic transplanted peripheral blood-derived iPS cell stock instead of autologous transplanted human T cell-derived iPS cells. When TCR with antigen information was introduced in producing killer T cells from iPS cell stock, it was possible to produce killer T cells with stable antigen specificity by itself.

　This study reveals that TCR stabilizing techniques prevent a decrease in antigen specificity of killer T cells, and that killer T cells with stable TCR from both the patient's own cells and cells in the iPS cell stock. Was realized.Based on this result, it is expected that cancer immunotherapy using iPS cell-derived T cells will be put into practical use.

Paper information:[Cell Stem Cell] Enhancing T Cell Receptor Stability in Rejuvenated iPSC-Derived T Cells Improves Their Use in Cancer Immunotherapy