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

• 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
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08671445/
• 关键词: pancreatic cancer; cytotoxic T lymphocyte; MUC1; liver metastasis; adoptive immunotherapy; postoperative administration; MUC1抗原; MUC1特異的CTL; 免疫組織染色; pancreatic cancer; cytotoxic T lymphocyte; MUC1; liver metastasis; adoptive immunotherapy; postoperative administration; MUC1抗原; MUC1特異的CTL; 免疫組織染色

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

在55个胰腺导管腺癌，2个正常的胰腺样本，3个慢性胰腺炎，I胰腺的导管增生，3个粘液性囊肿瘤胞瘤和2个肝脏转移的p Cancincin cincincin cincarcin cincincin cincarcin cincin cincincin中，在55个胰腺导管腺癌，2个正常的胰腺样本，3个慢性胰腺炎，I导管增生中检查了硫酸化的MUC1粘蛋白的表达。用新的单克隆抗体（MAB）通过免疫组织化学评估表达（MY.1E12）。在所有导管癌中，在癌细胞膜中表达脱糖的MUC1粘蛋白。当这些是管形成时，在细胞的顶端看到了反应产物。在粘液性囊这瘤中也检测到了这种模式。然而，它在单个癌细胞或没有管形成和转移性肝肿瘤中的细胞中的细胞膜中扩散。也就是说，入侵或转移性癌细胞在整个细胞膜中表达了这种类型的粘蛋白。在正常胰腺，慢性胰腺…更多的TIS或胰腺导管增生的标本中未观察到溶解的MUC1粘蛋白的表达。在正常胰腺中，这些溶解的MUC1的病变表达仅限于acini和分泌的粘蛋白。在胰腺癌患者中诱导了整个癌细胞膜上表达的硫酸化的MUC1粘蛋白，可能是胰腺导管腺癌的转移性潜在的一个因素。淋巴结腺癌（CTL）对MUC1的转移潜力。通过粘液表达的人胰腺癌细胞系YPK-1刺激的外周血单核细胞诱导CTL，添加了白介素2。有趣的是，这些CTL与常规CTL不同，以HLA无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，无法切除的8）。在无法切除的肿瘤患者中观察到了一点影响。但是，没有一个患者接受治疗切除术并在手术后接受GTL的治疗。这些结果表明，使用MUC1识别的CTL的适应性免疫疗法对于接受治疗切除术的胰腺癌患者可能很有用。较少的