Clinical Study of Immunotherapy at Pre-, Peri- and Psot-operation Applied ATK Activity to Lung Cancer

肺癌术前、围术期和术后应用 ATK 活性免疫治疗的临床研究

• 批准号: 07671462
• 负责人: KATO Hirofumi
• 金额: $ 1.47万
• 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: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07671462/
• 关键词: Adoptive immunotherapy; MUC-1; Cytotoxic T Lymphocyte; Lung Cancer; Synthetic Peptide; ATK活性

MUC-1 molecule is a mucin protein expressed on paticular cancer cell surface and thought to be an important tumor antigen. In this study we have attempted to induce cytotoxic T lymphocyte (CTL) using synthetic peptide of MUC-1 and analyzed the specificity for this molecyle.Peripheral blood mononuclear cell (PBMC) from lung cancer patients or normal donors was pulsed with the peptide and cultured in the presence of IL-7. The cell were re-stimulated with peptide-pulsed and irradiated PBMC every one week and cultured in the presence of IL-7 and IL-2. The MUC-1 specific activity of the induced CTL was tested at the end of 4th cycle of re-stimulateion. COLs had a strong cytotoxic acitivity against MUC-1 expressing MLC and T47D,and this activity was not inhibited by adding cold K562 which was sensitive to natural killar cells. And a cytotoxic activity of the CTLs was observed against MUC-1 transfectant whereas few activity was against the wild cell (MUC-1 deficient cell). These data show that the CTLs are specific for MUC-1.Clinical study of the adoptive immunotherapy was performed to 2 advanced lung cancer patients with the CTLs using MUC-1 peptide. Clinical symptons were improved and tumor maker (CEA) level was decreased on both patients administered the CTLs. And severe side effects were not observed.This methods was thought tobe useful for the purpose of immunotherapy for lung cancer.

MUC-1分子是在特定癌细胞表面表达的粘蛋白蛋白，被认为是重要的肿瘤抗原。在本研究中，我们尝试使用 MUC-1 合成肽诱导细胞毒性 T 淋巴细胞 (CTL)，并分析该分子的特异性。使用该肽脉冲来自肺癌患者或正常供体的外周血单核细胞 (PBMC)，并在 IL-7 存在的情况下培养。每周用肽脉冲和照射的 PBMC 重新刺激细胞，并在 IL-7 和 IL-2 存在的情况下培养。在第四个再刺激周期结束时测试诱导的CTL的MUC-1比活性。 COLs对表达MUC-1的MLC和T47D具有较强的细胞毒活性,且添加对自然杀伤细胞敏感的冷K562不抑制这种活性。观察到 CTL 对 MUC-1 转染子具有细胞毒活性，而对野生细胞（MUC-1 缺陷细胞）几乎没有活性。这些数据表明CTL对MUC-1具有特异性。使用MUC-1肽对2名患有CTL的晚期肺癌患者进行了过继免疫治疗的临床研究。接受 CTL 治疗的两名患者的临床症状均得到改善，肿瘤标志物 (CEA) 水平也有所降低。并且没有观察到严重的副作用。该方法被认为可用于肺癌的免疫治疗。