Reference - Detail
| RRC ID | 54734 |
|---|---|
| Author | Minagawa A, Yoshikawa T, Yasukawa M, Hotta A, Kunitomo M, Iriguchi S, Takiguchi M, Kassai Y, Imai E, Yasui Y, Kawai Y, Zhang R, Uemura Y, Miyoshi H, Nakanishi M, Watanabe A, Hayashi A, Kawana K, Fujii T, Nakatsura T, Kaneko S. |
| Title | Enhancing T Cell Receptor Stability in Rejuvenated iPSC-Derived T Cells Improves Their Use in Cancer Immunotherapy. |
| Journal | Cell Stem Cell |
| Abstract |
Limited T cell availability and proliferative exhaustion present major barriers to successful T cell-based immunotherapies and may potentially be overcome through the use of "rejuvenated" induced pluripotent stem cells derived from antigen-specific T cells (T-iPSCs). However, strict antigen specificity is essential for safe and efficient T cell immunotherapy. Here, we report that CD8αβ T cells from human T-iPSCs lose their antigen specificity through additional rearrangement of the T cell receptor (TCR) α chain gene during the CD4/CD8 double positive stage of in vitro differentiation. CRISPR knockout of a recombinase gene in the T-iPSCs prevented this additional TCR rearrangement. Moreover, when CD8αβ T cells were differentiated from monocyte-derived iPSCs that were transduced with an antigen-specific TCR, they showed monoclonal expression of the transduced TCR. TCR-stabilized, regenerated CD8αβ T cells effectively inhibit tumor growth in xenograft cancer models. These approaches could contribute to safe and effective regenerative T cell immunotherapies. |
| Volume | 23(6) |
| Pages | 850-858.e4 |
| Published | 2018-12-6 |
| DOI | 10.1016/j.stem.2018.10.005 |
| PII | S1934-5909(18)30486-7 |
| PMID | 30449714 |
| MeSH | Animals CD8 Antigens / immunology* CD8-Positive T-Lymphocytes / immunology* Humans Immunotherapy* Induced Pluripotent Stem Cells / immunology* Mice Mice, Inbred NOD Mice, SCID Neoplasms / immunology Neoplasms / therapy* Receptors, Antigen, T-Cell / immunology* Tumor Cells, Cultured |
| IF | 21.464 |
| Times Cited | 21 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | Patent(IFI CLAIMS) |
| Total number of mentions | 73 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | HEV0060 PC-9(RCB4455) |