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

MUC-1分子是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。本研究用MUC-1合成肽段刺激肺癌患者和正常人外周血单个核细胞（PBMC），在IL-7存在下培养，观察其诱导细胞毒性T淋巴细胞（CTL）的作用，并分析其特异性。每一周用肽脉冲和辐射的PBMC再刺激细胞，并在IL-7和IL-2存在下培养。在第4次再刺激结束时检测诱导的CTL的MUC-1比活性。COLs对表达MUC-1的MLC和T47 D细胞具有较强的细胞毒活性，加入对自然杀伤细胞敏感的冷K562后，这种活性不受抑制。观察到CTL对MUC-1转染子具有细胞毒性活性，而对野生细胞（MUC-1缺陷细胞）几乎没有活性。这些结果表明，所获得的CTL对MUC-1具有特异性。我们对2例具有MUC-1特异性CTL的晚期肺癌患者进行了MUC-1肽过继免疫治疗的临床研究。临床症状得到改善，肿瘤标记物（CEA）水平下降的两名患者管理的CTL。该方法可用于肺癌的免疫治疗。

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.