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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

检测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例粘液性囊腺瘤和2例胰腺导管腺癌肝转移瘤中唾液酸化MUC 1的表达。用新的单克隆抗体（mAb）（MY.1E12）通过免疫组织化学评估表达。唾液酸化MUC 1粘蛋白在所有导管癌的癌细胞膜上表达。当这些是小管形成时，在细胞的顶端方面看到反应产物。粘液性囊腺瘤中也可检测到这种模式。然而，在单个癌细胞或小簇细胞中，以及在转移性肝肿瘤中，可在细胞膜上广泛观察到它。也就是说，侵入或转移的癌细胞在整个细胞膜上表达这种类型的粘蛋白。在正常胰腺、慢性胰腺炎和胰腺癌组织中均未观察到唾液酸化MUC 1的表达。 ...更多信息胰腺炎或胰腺导管增生。在正常胰腺和这些病变中，唾液酸化MUC 1的表达仅限于腺泡和分泌性粘蛋白。唾液酸化MUC 1粘蛋白在胰腺癌细胞膜上的表达可能与胰腺癌的转移潜能有关。通过用MUCi表达的人胰腺癌细胞系YPK-1刺激的外周血单个核细胞诱导CTL，加入白细胞介素-2。有趣的是，这些CTL直接识别MUC 1分子的HLA不受限制的方式不同于传统的CTL。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）。对不能手术切除的肿瘤有一定疗效。然而，接受根治性切除术并在术后接受GTL治疗的患者均未发生肝转移。这些结果表明，使用MUC 1识别的CTL的过继免疫治疗可能对接受根治性切除术的胰腺癌患者有用。少