Regeneration of antigen-specific T cells by using induced pluripotent stem cell (iPSC) technology. (18th October 2021)

• Record Type: Journal Article
• Authors: Kawamoto, Hiroshi; Masuda, Kyoko; Nagano, Seiji
• Is Part Of: International immunology. Volume 33:Number 12(2021)
• Page Start: 827
• Page End: 833
• Publication Date: 2021-10-18
• Subjects: adoptive cell therapy -- cancer immunotherapy -- cytotoxic T lymphocytes -- iPS cells -- T-cell receptor; Immunology -- Periodicals; 616.079
• DOI: 10.1093/intimm/dxab091
• Languages: English
• ISSNs: 0953-8178

Abstract

Abstract: In currently ongoing adoptive T-cell therapies, T cells collected from the patient are given back to the patient after ex vivo cell activation and expansion. In some cases, T cells are transduced with chimeric antigen receptor (CAR) or T-cell receptor (TCR) genes during the ex vivo culture period. Although such strategies have been shown to be effective in some types of cancer, there remain issues to be solved; these methods (i) are time-consuming, (ii) are costly and (iii) it is difficult to guarantee the quality because the products depend on patient-derived T cells. To address these issues, several groups including ours have developed methods in which cytotoxic cells are mass-produced by using induced pluripotent stem cell (iPSC) technology. For the regeneration of T cells, the basic idea is as follows: iPSCs produced from T cells inherit rearranged TCR genes, and thus all regenerated T cells should express the same TCR. Based on this idea, various types of T cells have been regenerated, including conventional cytotoxic T lymphocytes (CTLs), γδT cells, NKT cells and mucosal-associated invariant T (MAIT) cells. On the other hand, any cytotoxic cells can be used as the base cells into which CAR is introduced, and thus iPSC-derived NK cells have been developed. To apply the iPSC-based cell therapy in an allogeneic setting, the authors' group developed a method in which non-T-cell-derived iPSCs are transduced with exogenous TCR genes (TCR-iPSC method). This approach is being prepared for a clinical trial to be realized in Kyoto University Hospital, in which acute myeloid leukemia patients will be treated by the regenerated WT1 antigen-specific CTLs. Graphical Abstract: