DEVELOPMENT OF IMMUNOTHERAPY TARGETING MAGNEPROTEIN FOR LUNG CANCER

肺癌靶向磁蛋白免疫疗法的开发

• 批准号: 10671249
• 负责人: INOUE Shuhei
• 金额: $ 1.92万
• 依托单位: SHIGA UNIVERSITY OF MEDICAL SCIENCE
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10671249/
• 关键词: MAGE; lung cancer; tumor antigen; immunotherapy; 細胞傷害性Tリンパ球(CTL); 肺癌細胞株

We analyzed the antigenicity of MAGE protein expressed in cancer cells for the purpose of developing cancer immunotherapy of lung cancer. We attempted to examine the expression of MAGE antigens in tumors from patients with lung cancer, to induce tumor-specific T lymphocytes (CTL) and to establish lung cancer cell lines from resected tumors from the patients.As a result, approximately 30% of lung tumors from 20 patients with lung cancer were positive for MAGE mRNA expression. Peripheral blood lymphocytes (PBL) from one of the patients were stimulated in vitro with autologous dendritic cells (DC) which were loaded with autologous tumor lysate. After 5-stimulations, CTL expressing CD3+/CD4+ were induced. They lysed autologous DC loaded with autologous lysate by 51Cr-release assay. Also, we established 8 lung cancer cell lines by grafting the resected tumors into Scid mice subcutaneously. Using these cell lined as target cells in the cytotoxic assay allows us to assess recognition of naive MAGE antigens on the cancer cells by the CTL.The data suggest that MAGE antigens are highly expressed in lung cancer and have the antigenicity as a tumor antigen. The antigen is expected to be useful as a tumor antigen for therapeutic application of cancer immunotherapy.

本研究分析了肺癌细胞中表达的法师蛋白的抗原性，为肺癌的免疫治疗提供理论依据。本研究通过检测肺癌患者肿瘤组织中法师抗原的表达，诱导肿瘤特异性T淋巴细胞（tumor-specific T lymphocyte，CTL），建立肺癌细胞系，结果发现20例肺癌患者中约30%的肺癌组织中有法师mRNA的表达。其中一名患者的外周血淋巴细胞（PBL）在体外用负载自体肿瘤裂解物的自体树突状细胞（DC）刺激。经5次刺激后，诱导出表达CD 3 +/CD 4+的CTL。他们通过51 Cr-释放测定裂解负载有自体裂解物的自体DC。此外，我们建立了8个肺癌细胞株，通过皮下移植肿瘤到Scid小鼠。用这些细胞系作为靶细胞进行细胞毒试验，可以检测CTL对癌细胞表面幼稚法师抗原的识别，结果表明法师抗原在肺癌中高度表达，具有肿瘤抗原的抗原性。预期该抗原可用作肿瘤抗原用于癌症免疫疗法的治疗应用。