[Mass-Production of Tumor Antigen-Specific Cytotoxic T Lymphocytes Using the iPS Cell Technology-Development of "Off-the-Shelf T Cells"for the Use in Allogeneic Transfusion Settings].

In the tumor immunotherapy field, the adoptive immunotherapies, in which patient-derived T cells are strengthened ex vivo by activation or genetic modification, have been shown to be effective. However, some issues still remain to be solved. For example, it is not easy to efficiently expand tumor antigen-specific T cells, since they easily get exhausted during ex vivo culture. Moreover, these strategies are costly and time-consuming, because they are mainly conducted in autologous settings. To address these issues, we have been utilizing the induced pluripotent stem(iPS)cell technology. When iPS cells are established from tumor antigen-specific T cells, T cells regenerated from these iPS cells are expected to express the same T cell receptor(TCR)as the original T cells. In line with this concept, we succeeded in regenerating tumor antigen-specific cytotoxic T cells in 2013. We subsequently succeeded in developing a method by which very potent cytotoxic T lymphocytes are regenerated. We are now developing a strategy where non-T derived iPSCs are transduced with exogenous TCR gene efficacy and safety of which have been clinically tested. We plan to apply this approach to HLA haplotype-homozygous iPS cell stock lines, expecting that it will become possible to establish "off-the-shelf T cell" bank against various types of tumors.