論文 - 詳細
| RRC ID | 63627 |
|---|---|
| 著者 | Iriguchi S, Yasui Y, Kawai Y, Arima S, Kunitomo M, Sato T, Ueda T, Minagawa A, Mishima Y, Yanagawa N, Baba Y, Miyake Y, Nakayama K, Takiguchi M, Shinohara T, Nakatsura T, Yasukawa M, Kassai Y, Hayashi A, Kaneko S. |
| タイトル | A clinically applicable and scalable method to regenerate T-cells from iPSCs for off-the-shelf T-cell immunotherapy. |
| ジャーナル | Nat Commun |
| Abstract |
Clinical successes demonstrated by chimeric antigen receptor T-cell immunotherapy have facilitated further development of T-cell immunotherapy against wide variety of diseases. One approach is the development of "off-the-shelf" T-cell sources. Technologies to generate T-cells from pluripotent stem cells (PSCs) may offer platforms to produce "off-the-shelf" and synthetic allogeneic T-cells. However, low differentiation efficiency and poor scalability of current methods may compromise their utilities. Here we show improved differentiation efficiency of T-cells from induced PSCs (iPSCs) derived from an antigen-specific cytotoxic T-cell clone, or from T-cell receptor (TCR)-transduced iPSCs, as starting materials. We additionally describe feeder-free differentiation culture systems that span from iPSC maintenance to T-cell proliferation phases, enabling large-scale regenerated T-cell production. Moreover, simultaneous addition of SDF1α and a p38 inhibitor during T-cell differentiation enhances T-cell commitment. The regenerated T-cells show TCR-dependent functions in vitro and are capable of in vivo anti-tumor activity. This system provides a platform to generate a large number of regenerated T-cells for clinical application and investigate human T-cell differentiation and biology. |
| 巻・号 | 12(1) |
| ページ | 430 |
| 公開日 | 2021-1-18 |
| DOI | 10.1038/s41467-020-20658-3 |
| PII | 10.1038/s41467-020-20658-3 |
| PMID | 33462228 |
| PMC | PMC7814014 |
| MeSH | Animals Cell Culture Techniques / methods* Cell Differentiation / drug effects Cell Line, Tumor Chemokine CXCL12 / metabolism Culture Media / metabolism Culture Media / pharmacology Female Humans Imidazoles / pharmacology Immunotherapy, Adoptive / methods* Induced Pluripotent Stem Cells / physiology* Mice Neoplasms / immunology Neoplasms / therapy* Pyridines / pharmacology Receptors, Chimeric Antigen / immunology T-Lymphocytes, Cytotoxic / immunology T-Lymphocytes, Cytotoxic / transplantation* Xenograft Model Antitumor Assays |
| IF | 12.121 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 67 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | NALM-6(RCB1933) CCRF-CEM(RCB1980) |