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1998 Fiscal Year Final Research Report Summary

Adoptive immunotherapy using MUC1 specific cytotoxic T lymphocytes for pancreatic cancer

Research Project

Project/Area Number 08671445
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionYamaguchi University

Principal Investigator

OKA Masaaki  Yamaguchi University School of Medicine. Professor., 医学部, 教授 (70144946)

Co-Investigator(Kenkyū-buntansha) HAZAMA Shoichi  Yamaguchi University School of Medicine. Assistant., 医学部, 助手 (50253159)
Project Period (FY) 1996 – 1998
Keywordspancreatic cancer / cytotoxic T lymphocyte / MUC1 / liver metastasis / adoptive immunotherapy / postoperative administration
Research Abstract

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

  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] 岡 正朗: "膵癌の養子免疫療法" 日本消化器外科学会雑誌. 29. 1851-1855 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hirazawa K: "New technique for inducing reversible obstructive jaundice in the rat." Eur Surg Res. 29. 195-201 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yuji Masaki: "Sialylated MUC1 mucin expression in normal pancreas, benign pancreatic lesions, and pancreatic ductal adenocarcinoma." Hepato-Gastroenterology.(in Press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tomio Ueno: "Laparoxcopic distal pancreatectomy preserving the spleen." Surg Lapa Endoscop.(in Press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Akiyoshi Tanaka: "Possible mechanism for early delayed gastric emptying after pylorus preserving pancreatoduodenectomy in rats." J Smooth Muscle Res. (in Press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Katsutoshi Hirazawa: "Depressed cytotoxic activity of hepatic nonparenchymal cells in rats with obstructive jaundice." Surgery. (in Press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Masaaki Oka: "Adoptive immunotherapy for pancreatic cancer." Jpn J Gastroenterl Surg. 29. 1851-1855 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hirazawa K: "New technique for inducing reversible obstructive jaundice in the rat." Eur Surg Res. 29. 195-201 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yuji Masaki: "Sialylated MUC1 mucin expression in normal pancreas, benign pancreatic lesions, and pancreatic ductal adenocarcinoma." Hepato-Gastroenterology. (in Press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tomio Ueno.: "Laparoscopic distal pancreatectomy preserving the spleen." Surg Lapa Endoscop. (in Press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Akiyoshi Tanaka: "Possible mechanism for early delayed gastric emptying after pylorus preserving pancreatoduodenectomy in rats." J Smooth Muscle Res. (in Press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Katsutoshi Hirazawa: "Depressed cytotoxic activity of hepatic nonparenchymal cells in rats with obstructive jaundice." Surgery. (in Press).

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1999-12-08  

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