Clinical research on a new immunotherapy for the treatment of non-small cell lung cancer

新型免疫疗法治疗非小细胞肺癌的临床研究

• 批准号: 17591460
• 负责人: NAKAJIMA Jun
• 金额: $ 2.18万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17591460/
• 关键词: non-small cell lung cancer; gamma; delta - T lymphocyte; immunotherapy; clinical trial; safety; recommended dosage; anticancer effect; NKG2D

This study aimed to investigate the safety and antitumor effect of the new immunotherapy with activated autologous gamma delta T-lymphocyte (GDT) on the patients suffering from recurrent non-small cell lung cancer. Approximately 1000-folds increase of the number GDT, comprising 85 to 95% of whole cultured mononuclear cells, was observed. This GDT fraction expresses NKG2D, showing cytotoxic effect against MICA/B-positive non-small cell cancer (NSCLC) cell lines.Under the admission of IRB in this hospital, we started the clinical trial on the treatment of refractory NSCLC with activated autologous GDT. We registered 8 patients with recurrent NSCLC after the documented informed consent. All except for 2 patients who attained enough number of GDT after in vitro culture were assigned to this clinical investigation.We observed no harmful complications after administration of cultured GDT, except for one case who had suffered from common cold during the trial period, which were not related to the GDT therapy. We found that one of 3 patients who had undergone FACT-QOL questionnaire had exacerbation of QOL during the study, which were mainly due to the common cold.All of the patients had measurable foci of recurrence, which were not decreased in size by Computed tomography during the study. We performed flow-cytometry study of the peripheral blood of the patients undergoing GDT therapy, and we observed that number of GDT was increased during the therapy. We also observed cytotoxic effect of the GDT against U266 cell line which expresses MICA on the surface. We confirmed that NKG2D-MICA/B cytotoxic effect on GDT of the patients.In this study so far, we actually gave each patient the activated GDT only 4 times. We suggest that increment of the dosage of GDT would make breakthrough on the immunotherapy of NSCLC.

这项研究旨在研究新的免疫疗法的安全性和抗肿瘤作用，其激活的自体伽玛三角肌T淋巴细胞（GDT）对患有复发性非小细胞肺癌的患者。观察到数量GDT的数量增加了约1000倍，占整个培养的单核细胞的85％至95％。该GDT级分表达NKG2D，显示了针对MICA/B阳性非小细胞癌（NSCLC）细胞系的细胞毒性作用。在该医院接受IRB的情况下，我们开始对使用活性自动GDT治疗难治性NSCLC的临床试验。在记录下来的知情同意书后，我们注册了8例复发性NSCLC患者。除了2名在体外培养后获得足够数量的GDT的患者外，所有患者都被分配给了该临床研究。我们观察到培养的GDT后没有有害并发症，除了在试验期间与GDT治疗无关的一个病例遭受了普通感冒。我们发现，在研究期间接受了FACT-QOL调查表的3例患者中的一名患有QOL，这主要是由于常见的感冒。所有患者的复发焦点都可测量，在研究过程中，这些患者的复发焦点并未通过计算机断层扫描降低。我们对接受GDT治疗的患者的外周血进行了流动性研究研究，我们观察到治疗期间GDT的数量增加了。我们还观察到GDT对U266细胞系的细胞毒性作用，该细胞系在表面上表达云母。我们确认NKG2D-MICA/B细胞毒性对患者的GDT作用。在这项研究到目前为止，实际上，我们实际上只给了每个患者激活的GDT 4次。我们建议，GDT剂量的增加将使NSCLC的免疫疗法取得突破。

项目成果

高齢者の肺癌

老年人肺癌

• 发表时间: 2005
• 期刊: 日本老年医学会雑誌 42・6
• 作者: Goto A;Nakajima J;Hara K;Niki T;Fukayama M.;中島 淳;中島 淳
• 通讯作者: 中島 淳

呼吸器合併症を有する肺癌の治療

肺癌合并呼吸系统并发症的治疗

• 发表时间: 2006
• 期刊: 外科 68・4
• 作者: 中島 淳;垣見 和宏;村川 知弘;深見 武史;佐野 厚;日下部 将史;杉浦 未紀;高本 眞一;中島 淳
• 通讯作者: 中島 淳

Does preoperative transbronchial biopsy worsen the postsurgical prognosis of lung cancer? A propensity score-adjusted analysis

术前经支气管活检是否会恶化肺癌的术后预后？

• 发表时间: 2005
• 期刊: Chest. 128(5)
• 作者: Nakajima J.;Sato H.;Takamoto S.
• 通讯作者: Takamoto S.

自己γδ-T細胞療法の非小細胞肺癌に対する安全性および効果に関する臨床研究。

自体γδ-T细胞治疗非小细胞肺癌安全性和有效性的临床研究

• 发表时间: 2006
• 期刊: 肺癌 46・5
• 作者: 中島 淳;垣見 和宏;村川 知弘;深見 武史;佐野 厚;日下部 将史;杉浦 未紀;高本 眞一
• 通讯作者: 高本 眞一

Surgical treatment of the lung cancer in elderly patients (in Japanese)

老年肺癌的手术治疗（日语）

• 发表时间: 2005
• 期刊: Japanese Journal of Geriatrics 42(6)
• 作者: Nakajima J.;Sato H.;Takamoto S.;Nakajima J.
• 通讯作者: Nakajima J.