論文 - 詳細
| RRC ID | 82383 |
|---|---|
| 著者 | Yoshikawa T, Ito Y, Wu Z, Kasuya H, Nakashima T, Okamoto S, Amaishi Y, Zhang H, Li Y, Matsukawa T, Inoue S, Kagoya Y. |
| タイトル | Development of a chimeric cytokine receptor that captures IL-6 and enhances the antitumor response of CAR-T cells. |
| ジャーナル | Cell Rep Med |
| Abstract |
The efficacy of chimeric antigen receptor (CAR)-engineered T cell therapy is suboptimal in most cancers, necessitating further improvement in their therapeutic actions. However, enhancing antitumor T cell response inevitably confers an increased risk of cytokine release syndrome associated with monocyte-derived interleukin-6 (IL-6). Thus, an approach to simultaneously enhance therapeutic efficacy and safety is warranted. Here, we develop a chimeric cytokine receptor composed of the extracellular domains of GP130 and IL6RA linked to the transmembrane and cytoplasmic domain of IL-7R mutant that constitutively activates the JAK-STAT pathway (G6/7R or G6/7R-M452L). CAR-T cells with G6/7R efficiently absorb and degrade monocyte-derived IL-6 in vitro. The G6/7R-expressing CAR-T cells show superior expansion and persistence in vivo, resulting in durable antitumor response in both liquid and solid tumor mouse models. Our strategy can be widely applicable to CAR-T cell therapy to enhance its efficacy and safety, irrespective of the target antigen. |
| 巻・号 | 5(5) |
| ページ | 101526 |
| 公開日 | 2024-5-21 |
| DOI | 10.1016/j.xcrm.2024.101526 |
| PII | S2666-3791(24)00195-2 |
| PMID | 38670095 |
| PMC | PMC11148643 |
| MeSH | Animals Cell Line, Tumor Cytokine Receptor gp130 / metabolism Humans Immunotherapy, Adoptive* / methods Interleukin-6* / immunology Interleukin-6* / metabolism Mice Neoplasms / immunology Neoplasms / therapy Receptors, Chimeric Antigen* / immunology Receptors, Chimeric Antigen* / metabolism Receptors, Cytokine / genetics Receptors, Cytokine / metabolism Receptors, Interleukin-6 / metabolism Receptors, Interleukin-7 / metabolism T-Lymphocytes* / immunology T-Lymphocytes* / metabolism Xenograft Model Antitumor Assays |
| 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 | X(Twitter) |
| 各媒体での言及数の合計 | 9 |
| 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 | |
| 研究用ヒト臍帯血幹細胞 | NALM-6(RCB1933) |