Identification of tumor-associated antigen in malignant pleural mesothelioma for establishment of tumor specific immunotherapy.

恶性胸膜间皮瘤中肿瘤相关抗原的鉴定，用于建立肿瘤特异性免疫治疗。

• 批准号: 21591829
• 负责人: SOU Tetuya
• 金额: $ 2.91万
• 依托单位: University of Occupational and Environmental Health, Japan
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21591829/
• 关键词: 悪性胸膜中皮腫; 細胞障害性T細胞; 腫瘍浸潤リンパ球; SEREX法; Thrombosposqoudin 2; 腫瘍マーカー; 腫瘍免疫; Thrombospoudin 2; 細胞性免疫; 液性免疫; 細胞障害性Tリンパ球(CTL); 腫瘍細胞株; cDNA発現スクリーニング法; modified SEREX法; SCIDマウス血清中ヒト型IgG

Malignant pleural mesothelioma(MPM) is difficult to diagnose at an early stage. The present study attempted to identify tumor-associated antigen, which is applicable for surrogate biomarkers of diagnosis or for antigen-targeted therapy for MPM.Bulk cytotoxic T lymphocytes(CTL) were induced successfully by co-culture of lymphocytes and the autologous MPM cell line L324MSO. Then, CTL clone was established by the limiting dilution method. CTL clone showed cytotoxic activity against L324MSO, but not autologous PHA blast or K562 in an HLA-restricted manner. Using the CTL clone, an antigen-coding gene has been screened using the cDNA expression cloning technique.On the other hand, tumor-associated antigens were also identified by using antibody derived from tumor-infiltrating B lymphocytes in MPM. Immunoscreening of the cDNA libraries was carried out by serological identification of antigens by a recombinant expression cloning method(SEREX), and 2 antigens were identified as MPM-associated antigens(Gene-X and thrombospondin-2(THBS-2)). Antibodies against Gene-X and THBS-2 in the sera were measured by ELISA method. A total of 124 sera were investigated ; 97 patients were finally diagnosed with MPM and 27 were diagnosed as non-malignant diseases(NM). The serum antibody-titer against THBS-2 was significantly higher in MPM patients than in NM(P<0.01), but there was no difference in the serum antibody-titer against Gene-X. The serum antibody-titer against THBS-2 was a useful non-invasive marker in the diagnosis of MPM. Furthermore, the suppression of Gene-X and THBS-2 expression by transfection with small interfering RNA resulted in suppression of the cell cycle associated gene and apoptosis associated gene, and the growth inhibition of MPM cell lines. These results may indicate that Gene-X and THBS-2 are may be a useful candidate as a target for specific immunotherapy.

恶性胸膜间皮瘤（MPM）在早期很难诊断。本研究试图鉴定与肿瘤相关的抗原，该抗原适用于诊断的替代生物标志物或用于MPmmmmmm.ulk细胞毒性T淋巴细胞（CTL）的替代生物标志物（CTL），通过淋巴细胞和自动MPM Cell系列成功地诱导L324MSO。然后，通过限制稀释法建立了CTL克隆。 CTL克隆以HLA限制的方式显示出针对L324MSO的细胞毒性活性，但没有自体PHA BLAST或K562。使用CTL克隆，已经使用cDNA表达克隆技术对抗原编码基因进行了筛选。另一方面，还使用源自MPM中肿瘤浸润B淋巴细胞的抗体来鉴定肿瘤相关的抗原。通过重组表达克隆法（SEREX）（SEREX）对抗原的血清学鉴定进行了cDNA文库的免疫统计，并将2个抗原鉴定为MPM相关的抗原（Gene-X和Thrombospondin-2（THBS-2））。通过ELISA方法测量血清中针对基因-X和THBS-2的抗体。总共研究了124种血清；最终被诊断为97例MPM，27例被诊断为非恶性疾病（NM）。在MPM患者中，针对THBS-2的血清抗体滴度明显高于NM（p <0.01），但针对Gene-X的血清抗体滴体没有差异。在MPM诊断中，针对THBS-2的血清抗体滴剂是一种有用的非侵入性标记。此外，通过小型干扰RNA转染对基因-X和THBS-2表达的抑制导致细胞周期相关基因和凋亡相关基因的抑制，以及MPM细胞系的生长抑制。这些结果可能表明Gene-X和THBS-2可能是有用的候选者作为特定免疫疗法的靶标。

项目成果

悪性胸膜中皮腫に対する腫瘍特異的免疫応答の解析

恶性胸膜间皮瘤的肿瘤特异性免疫反应分析

• 发表时间: 2010
• 作者: Kanno C;et al.;Nose N.;北中千史;Kitanaka C;花桐武志;花桐武志;Nagata Y.;Shigematsu Y.;Yasumoto K.;花桐武志;竹之山光広
• 通讯作者: 竹之山光広

竹之山光広,花桐武志,安元公正:悪性胸膜中皮腫関連抗原の同定と機能解析

Mitsuhiro Takenoyama、Takeshi Hanagiri、Masaru Yasumoto：恶性胸膜间皮瘤相关抗原的鉴定和功能分析

• 发表时间: 2010
• 作者: 重松義紀;黒田耕志;馬場哲郎;宗哲哉;安田学;小野憲司;浦本秀隆;宗知子;竹之山光広;花桐武志;安元公正
• 通讯作者: 安元公正

Immunotherapy for Lung Cancer

• DOI: 10.37047/jos.2022-92712
• 发表时间: 2023
• 期刊: Journal of Oncological Sciences
• 作者: N. Karadurmuş;N. Akyürek;A. Aydıner;R. Savaş;Özlem Sönmez;M. Şendur;B. Oyan;D. Yalman;Mehmet Ufuk Yilmaz;Ülkü Yılmaz;P. Yumuk;E. Göker

Results of Surgical Treatment for Patients with Small Cell Lung Cancer

• DOI: 10.1097/jto.0b013e3181a8cd84
• 发表时间: 2009-08-01
• 期刊: JOURNAL OF THORACIC ONCOLOGY
• 影响因子: 20.4
• 作者: Hanagiri, Takeshi;Sugio, Kenji;Yasumoto, Kosei
• 通讯作者: Yasumoto, Kosei

癌精巣抗原KK-LC-1を認識するT細胞受容体移入γδT細胞を用いた養子免疫療法への応用

使用识别癌睾丸抗原 KK-LC-1 的 T 细胞受体转移 γδT 细胞在过继性免疫治疗中的应用

• 发表时间: 2010
• 作者: 松本智晴;鳥越千秋;岩穴口孝;村永文学;宇都由美子;熊本一朗;黒田耕志,竹之山光広,馬場哲郎,重松義紀,宗哲哉,市来嘉伸,小野憲司,安田学,菅谷将一,浦本秀隆,宗知子,花桐武志,安元公正;松本智晴;重松義紀,黒田耕志,馬場哲郎,宗哲哉,安田学,小野憲司,浦本秀隆,宗知子,竹之山光広,花桐武志,安元公正;松本智晴;黒田耕志,竹之山光広,塩田広宣,馬場哲郎,重松義紀,宗哲哉,水上真紀子,市来嘉伸,小野憲司,安田学,菅谷将一,浦本秀隆,宗知子,花桐武志,安元公正;松本智晴;重松義紀,塩田広宣,黒田耕志,馬場哲郎,宗哲哉,小野憲司,浦本秀隆,宗知子,竹之山光広,花桐武志,安元公正
• 通讯作者: 重松義紀,塩田広宣,黒田耕志,馬場哲郎,宗哲哉,小野憲司,浦本秀隆,宗知子,竹之山光広,花桐武志,安元公正