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

muc1分子是一种表达于特定癌细胞表面的粘蛋白，被认为是重要的肿瘤抗原。在本研究中，我们尝试用合成的MUC-1肽诱导细胞毒性T淋巴细胞（CTL），并分析了该分子的特异性。将肺癌患者或正常供者的外周血单核细胞（PBMC）用该肽脉冲并在IL-7存在下培养。每隔一周用肽脉冲和辐照的PBMC再刺激细胞，并在IL-7和IL-2的存在下培养。在第4个再刺激周期结束时检测诱导CTL的MUC-1特异性活性。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态K562不抑制这种活性。ctl对muc1转染细胞有一定的细胞毒活性，而对野生细胞（muc1缺陷细胞）没有明显的细胞毒活性。这些数据表明ctl对MUC-1具有特异性。应用MUC-1肽对2例晚期肺癌ctl患者进行过继免疫治疗的临床研究。两组患者的临床症状均有改善，肿瘤生成因子（CEA）水平均有降低。没有观察到严重的副作用。这种方法被认为对肺癌的免疫治疗是有用的。

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.