Establishment of tumor specific immunotherapy for lung cancer patients ; Identification of tumor antigens and analysis of immune responses.

肺癌患者肿瘤特异性免疫治疗的建立；

• 批准号: 14370420
• 负责人: YASUMOTO Kosei
• 金额: $ 8.96万
• 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 (B)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14370420/
• 关键词: Lung cancer; tumor antigen; peptide; CTL; SEREX; immunotherapy; vaccine; antibody

It is very important to analyze tumor-specific immune responses in cancer patients for development of effective tumor specific immunotherapy. We have established 21 lung cancer cell lines and induced tumor-specific cytotoxic T lymphocytes (CTL) from regional lymph node lymphocytes in lung cancer patients. Several tumor associate antigens recognized by these CTLs were identified by cDNA expression cloning method. CTL Clone 1 and Clone 2 recognized autologous large cell carcinoma (A904L), whereas they did not respond to autologous EBV-B and PHA-blastoid T cells. Clone 1 recognized the tumor antigen restricted by HLA-A24. The antigen coding gene revealed a splicing variant of known gene. On the other hand, Clone 2 recognized the tumor antigen in the context of HLA-Cw7. The antigen coding gene was a function-unknown gene. The tumor specific CTL clone H1 against adenocarcinoma cell line (F1121L) was induced from regional lymph node lymphocytes. This CTL clone lysed autologous tumor cells in … More the context of HLA-B^*1507. The antigen recognized by the CTL was a new cancer/testis antigen. Identification of these lung cancer associated antigen facilitates peptide based specific immunotherapy for lung cancer patients.In order to investigate the potential role of tumor-infiltrating B cells (TIB) in lung cancer, we demonstrated that humoral immune responses of TIB in lung cancer patients could be detected in SLID mice xenotransplanted model. By serological analysis of recombinant cDNA expression libraries (SERER), 25 distinct antigens reactive with IgG derived from TIB were identified in two lung cancer cell lines. Sequencing analysis showed that the functions of 14 antigens were known, and the function of other 11 genes were unknown. Furthermore, 4 out of the identified genes had extra-cellular region. These findings suggested that TIB-derived IgG played an important role in humoral immune response against lung cancer. The identified cancer related antigens may have a potential target for cancer vaccines and monoclonal antibody-based immunotherapies. Less

肿瘤特异性免疫应答的研究对于肿瘤特异性免疫治疗的研究具有重要意义。我们建立了21株肺癌细胞系，并从肺癌患者局部淋巴结淋巴细胞中诱导出肿瘤特异性细胞毒性T淋巴细胞（CTL）。用cDNA表达克隆法鉴定了这些CTL所识别的肿瘤相关抗原。CTL克隆1和克隆2识别自体大细胞癌（A904 L），而它们对自体EBV-B和PHA-胚样T细胞没有应答。克隆1识别受HLA-A24限制的肿瘤抗原。抗原编码基因显示已知基因的剪接变体。另一方面，克隆2识别HLA-Cw 7背景下的肿瘤抗原。抗原编码基因为功能未知基因。从局部淋巴结淋巴细胞中诱导出抗人肺腺癌细胞系（F1121 L）的肿瘤特异性CTL克隆H1。该CTL克隆裂解自体肿瘤细胞， ...更多信息 HLA-B^*1507的背景。CTL所识别的抗原是一种新的肿瘤/睾丸抗原。为了研究肿瘤浸润B细胞（TI B cells）在肺癌发病中的作用，我们在SLID小鼠肺癌移植模型中检测到TI B细胞的体液免疫应答。通过对重组cDNA表达文库（SERER）的血清学分析，在两种肺癌细胞系中鉴定出25种与TIB来源的IgG反应的不同抗原。测序结果表明，14个抗原基因的功能已知，11个基因的功能未知。此外，在所鉴定的基因中，有4个具有细胞外区域。提示TIB源IgG在肺癌体液免疫应答中起重要作用。所鉴定的癌症相关抗原可能具有癌症疫苗和基于单克隆抗体的免疫疗法的潜在靶点。少

项目成果

Simultaneously cellular and humoral immune response against mutated p53 in a patient with ling cancer

ling 癌患者针对突变 p53 的同时细胞和体液免疫反应

• 发表时间: 2004
• 期刊: J Immunology 172
• 作者: Ichiki Y

Tumor specific expression of survivin-2B in lung cancer as a novel target of immunotherapy

• DOI: 10.1016/j.lungcan.2004.10.017
• 发表时间: 2005-05-01
• 期刊: LUNG CANCER
• 影响因子: 5.3
• 作者: Ichiki, Y;Hanagiri, T;Yasumoto, K
• 通讯作者: Yasumoto, K

Gu CD: "Detection of micrometastatic fumor cells in pNO lymph nodes of patients with completely resected nonsmall cell lung cancer : impact on recurrence and Survival"Ann Surg. 235・1. 133-139 (2002)

Gu CD：“完全切除的非小细胞肺癌患者 pNO 淋巴结中微转移肿瘤细胞的检测：对复发和生存的影响”Ann Surg 235・1（2002）。

肺癌浸潤過程における接着分子の関与とその情報伝達による免疫回避機構の解析

粘附分子参与肺癌侵袭过程及信息传递的免疫逃避机制分析

• 发表时间: 2003
• 期刊: Biotherapy 17(2)
• 作者: Yasuda M

Tumor-infiltrating B lymphocytes as a potential source of identifying tumor antigen in human lung cancer.

• 发表时间: 2002-03
• 期刊: Cancer research
• 影响因子: 11.2
• 作者: M. Yasuda;M. Takenoyama;Y. Obata;M. Sugaya;T. So;T. Hanagiri;K. Sugio;K. Yasumoto