論文 - 詳細
| RRC ID | 38581 |
|---|---|
| 著者 | Sakamoto M, Nakajima J, Murakawa T, Fukami T, Yoshida Y, Murayama T, Takamoto S, Matsushita H, Kakimi K. |
| タイトル | Adoptive immunotherapy for advanced non-small cell lung cancer using zoledronate-expanded γδTcells: a phase I clinical study. |
| ジャーナル | J Immunother |
| Abstract |
Human γδ T cells can recognize and kill non-small cell lung cancer (NSCLC) cells using the Vγ9Vδ2 T-cell receptor and/or NKG2D. We have established clinical grade large-scale ex vivo expansion of γδ T cells from peripheral blood mononuclear cells by culturing with zoledronate and interleukin-2 (IL-2). A phase I study was conducted to evaluate safety and potential antitumor effects of re-infusing ex vivo expanded γδ T cells in patients with recurrent or advanced NSCLC. Patient's peripheral blood mononuclear cells were stimulated with zoledronate (5 μM) and IL-2 (1000 IU/mL) for 14 days. Harvested cells, mostly γδ T cells, were given intravenously every 2 weeks without additional IL-2, a total of 6 times. The cumulative number of transferred γδ T cells ranged from 2.6 to 45.1 x 10⁹ (median, 15.7×10⁹). Fifteen patients underwent adoptive immunotherapy with these γδ T cells. There were no severe adverse events related to the therapy. Immunomonitoring data showed that with increasing numbers of infusions, the number of peripheral γδ T cells gradually increased. All patients remained alive during the study period with a median survival of 589 days and median progression-free survival of 126 days. According to the Response Evaluation Criteria In Solid Tumors, there were no objective responses. Six patients had stable disease, whereas the remaining 6 evaluable patients experienced progressive disease 4 weeks after the sixth transfer. We conclude that adoptive transfer of zoledronate-expanded γδ T cells is safe and feasible in patients with NSCLC, refractory to other treatments. |
| 巻・号 | 34(2) |
| ページ | 202-11 |
| 公開日 | 2011-3-1 |
| DOI | 10.1097/CJI.0b013e318207ecfb |
| PMID | 21304399 |
| MeSH | Adult Aged Aged, 80 and over Bone Density Conservation Agents / pharmacology Carcinoma, Non-Small-Cell Lung / immunology Carcinoma, Non-Small-Cell Lung / pathology Carcinoma, Non-Small-Cell Lung / therapy* Cell Proliferation / drug effects* Cytotoxicity, Immunologic / drug effects Diphosphonates / pharmacology* Female Humans Imidazoles / pharmacology* Immunotherapy, Adoptive* Interleukin-2 / pharmacology Male Middle Aged Neoplasm Staging Quality of Life T-Lymphocytes / drug effects* T-Lymphocytes / immunology Treatment Outcome Zoledronic Acid |
| IF | 2.985 |
| 引用数 | 13 |
| WOS 分野 | BIOPHYSICS BIOCHEMISTRY & MOLECULAR BIOLOGY |
| 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 | 5 |
| 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 | DAUDI(RCB1640) |