論文 - 詳細
| RRC ID | 64115 |
|---|---|
| 著者 | Saito S, Harada Y, Morodomi Y, Onimaru M, Yoshida K, Kyuragi R, Matsubara H, Yonemitsu Y. |
| タイトル | Ex vivo generation of highly purified and activated natural killer cells from human peripheral blood. |
| ジャーナル | Hum Gene Ther Methods |
| Abstract |
Adoptive immunotherapy using natural killer (NK) cells has been a promising treatment for intractable malignancies; however, there remain a number of difficulties with respect to the shortage and limited anticancer potency of the effector cells. We here established a simple feeder-free method to generate purified (>90%) and highly activated NK cells from human peripheral blood-derived mononuclear cells (PBMCs). Among the several parameters, we found that CD3 depletion, high-dose interleukin (IL)-2, and use of a specific culture medium were sufficient to obtain highly purified, expanded (∼200-fold) and activated CD3(-)/CD56(+) NK cells from PBMCs, which we designated zenithal-NK (Z-NK) cells. Almost all Z-NK cells expressed the lymphocyte-activated marker CD69 and showed dramatically high expression of activation receptors (i.e., NKG2D), interferon-γ, perforin, and granzyme B. Importantly, only 2 hours of reaction at an effector/target ratio of 1:1 was sufficient to kill almost all K562 cells, and the antitumor activity was also replicated in tumor-bearing mice in vivo. Cytolysis was specific for various tumor cells, but not for normal cells, irrespective of MHC class I expression. These findings strongly indicate that Z-NK cells are purified, expanded, and near-fully activated human NK cells and warrant further investigation in a clinical setting. |
| 巻・号 | 24(4) |
| ページ | 241-52 |
| 公開日 | 2013-8-1 |
| DOI | 10.1089/hgtb.2012.183 |
| PMID | 23885718 |
| PMC | PMC3753730 |
| MeSH | Animals Antigens, CD / genetics Antigens, CD / metabolism Antigens, Differentiation, T-Lymphocyte / genetics Antigens, Differentiation, T-Lymphocyte / metabolism Female Flow Cytometry / methods* Humans Interferon-gamma / genetics Interferon-gamma / metabolism K562 Cells Killer Cells, Lymphokine-Activated / cytology* Killer Cells, Lymphokine-Activated / immunology Killer Cells, Lymphokine-Activated / metabolism Lectins, C-Type / genetics Lectins, C-Type / metabolism Mice Mice, Inbred NOD Xenograft Model Antitumor Assays |
| IF | 2.446 |
| 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 | 26 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 3.0 |
| リソース情報 | |
| ヒト・動物細胞 | MRC-5 |