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Adoptive immunotherapy using MUC1 specific cytotoxic T lymphocytes for pancreatic cancer

使用 MUC1 特异性细胞毒性 T 淋巴细胞治疗胰腺癌的过继免疫疗法

基本信息

批准号：
08671445
负责人：
OKA Masaaki
金额：
$ 1.66万
依托单位：
Yamaguchi University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1998
项目状态：
已结题

项目摘要

The expression of sialylated MUC1 mucin was examined in 55 pancreatic ductal adenocarcinomas, 2 normal pancreas specimens, 3 chronic pancreatitis specimens, I ductal hyperplasia of the pancreas, 3 mucinous cystadenomas, and 2 liver metastases from pancreatic ductal adenocarcinoma. Expression was assessed by immunohistochemistry with a new monoclonal antibody (mAb) (MY.1E12). Sialylated MUC1 mucin was expressed in the cancer cell membrane in all the ductal carcinomas. The reaction product was seen at the apical aspect of cells when these was tubule formation. This pattern was also detected in mucinous cystadenomas. However, it was seen diffusely in the cell membrane in single cancer cells or small clusters of cells without tubule formation and in metastatic liver tumors. Namely, invading or metastatic cancer cells expressed this type of mucin throughout the entire cell membrane. The expression of sialylated MUC1 mucin was not observed in specimens from normal pancreas, chronic pancreati … More tis, or ductal hyperplasia of the pancreas. In normal pancreas and these lesions expression of sialylated MUC1 was limited to acini and secreted mucin. Sialylated MUC1 mucin which expressed throughout the cancer cell membrane may be a factor in the metastatic potential of pancreatic ductal adenocarcinoma.Cytotoxic T lymphocytes (CTLs) against MUC1 was induced in pancreas cancer patients. CTLs were induced by peripheral blood mononuclear cells stimulated by MUCi-expressed human pancreatic cancer cell line, YPK-1, added interleukin-2. Interestingly, these CTLs directly recognized MUC1 molecules in an HLA-unrestricted manner unlike conventional CTLs. We treated patients with 18 pancreatic cancer (resectable 10, unresectable 8) using these CTLs. A little effects were observed in patients with unresectable tumors. However, none of patient who underwent curative resection and was treated by GTLs after surgery had liver metastasis. These results indicated that adoptive immunotherapy using MUC1 recognized CTLs could be useful for pancreatic cancer patients who underwent curative resection. Less

我们在55例胰腺导管腺癌、2例正常胰腺、3例慢性胰腺炎、1例胰腺导管增生、3例粘液囊腺瘤和2例胰腺导管腺癌肝转移灶中检测了唾液化MUC1粘蛋白的表达。免疫组织化学检测新的单克隆抗体（MY.1E12）的表达。唾液化MUC1粘蛋白在所有导管癌的细胞膜上均有表达。当这些细胞是小管形成时，反应产物可见于细胞的顶端。黏液性囊腺瘤也有这种表现。然而，在单个癌细胞或没有小管形成的小簇细胞和转移性肝肿瘤的细胞膜中可见弥漫性。也就是说，侵袭或转移的癌细胞在整个细胞膜上表达这种粘蛋白。在正常胰腺、慢性胰腺炎和胰腺导管增生的标本中均未观察到唾液化MUC1粘蛋白的表达。在正常胰腺和这些病变中，唾液化MUC1的表达仅限于腺泡和分泌的粘蛋白。唾液化的MUC1粘蛋白在整个癌细胞膜上表达，可能是胰腺导管腺癌转移潜力的一个因素。在胰腺癌患者体内诱导抗MUC1的细胞毒性T淋巴细胞（ctl）。用muci表达的人胰腺癌细胞系YPK-1和白细胞介素-2刺激外周血单个核细胞诱导ctl。有趣的是，与传统的ctl不同，这些ctl以不受hla限制的方式直接识别MUC1分子。我们使用这些ctl治疗了18例胰腺癌患者（可切除10例，不可切除8例）。对于无法切除的肿瘤患者，疗效甚微。然而，手术后接受根治性切除和gtl治疗的患者均未发生肝转移。这些结果表明，使用MUC1识别的ctl进行过继免疫治疗可能对接受根治性切除的胰腺癌患者有用。少