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.

本研究旨在探讨活化自体γ δ t淋巴细胞（GDT）免疫治疗复发性非小细胞肺癌患者的安全性和抗肿瘤效果。观察到GDT的数量增加了约1000倍，占整个培养的单个核细胞的85%至95%。该GDT片段表达NKG2D，显示出对MICA/ b阳性非小细胞癌（NSCLC）细胞系的细胞毒作用。在我院IRB住院期间，我们开展了活化自体GDT治疗难治性NSCLC的临床试验。我们登记了8例经书面知情同意的复发性非小细胞肺癌患者。除2例体外培养后GDT达到足够数量的患者外，其余患者均被分配到本临床研究中。除1例患者在试验期间出现与GDT治疗无关的普通感冒外，我们未观察到培养GDT治疗后的有害并发症。我们发现，在接受FACT-QOL问卷调查的3例患者中，有1例患者在研究期间出现了生活质量恶化，其主要原因是普通感冒。所有患者都有可测量的复发灶，在研究期间，计算机断层扫描显示复发灶的大小没有减小。我们对接受GDT治疗的患者外周血进行了流式细胞术研究，我们观察到GDT的数量在治疗过程中增加。我们还观察了GDT对表面表达MICA的U266细胞株的细胞毒作用。我们证实了NKG2D-MICA/B对患者GDT的细胞毒性作用。在目前的研究中，我们实际上只给每个患者4次激活的GDT。我们认为增加GDT的剂量将在非小细胞肺癌的免疫治疗上取得突破。

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.