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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
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 1998: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1997: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1996: ¥1,600,000 (Direct Cost: ¥1,600,000)
Keywordspancreatic 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
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

Report

(4 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • 1996 Annual Research Report
  • Research Products

    (24 results)

All Other

All Publications (24 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
    • Related Report
      1998 Final Research Report Summary
  • [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
    • Related Report
      1998 Final Research Report Summary
  • [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
    • Related Report
      1998 Final Research Report Summary
  • [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
    • Related Report
      1998 Final Research Report Summary
  • [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
    • Related Report
      1998 Final Research Report Summary
  • [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
    • Related Report
      1998 Final Research Report Summary
  • [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
    • Related Report
      1998 Final Research Report Summary
  • [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
    • Related Report
      1998 Final Research Report Summary
  • [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
    • Related Report
      1998 Final Research Report Summary
  • [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
    • Related Report
      1998 Final Research Report Summary
  • [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
    • Related Report
      1998 Final Research Report Summary
  • [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
    • Related Report
      1998 Final Research Report Summary
  • [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)

    • Related Report
      1998 Annual Research Report
  • [Publications] Hirazawa K: "New technique for inducing reversible obstructive jaundice in the rat." Eur Surg Res. 29. 195-201 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yuji Masaki: "Sialylated MUC1 mucin expression in normal pancreas,benign pancreatic lesions,and pancreatic ductal adenocarcinoma." Hepato-Gastroenterology. (in Press).

    • Related Report
      1998 Annual Research Report
  • [Publications] Tomio Ueno: "Laparoscopic distal pancreatectomy preserving the spleen." Surg Lapa Endoscop. (in Press).

    • Related Report
      1998 Annual Research Report
  • [Publications] Akiyoshi Tanaka: "Possible mechanism for early delayed gastric emptying after pylorus preserving pancreatoduodenectomy in rats." J Smooth Muscle Res. (in Press).

    • Related Report
      1998 Annual Research Report
  • [Publications] Katsutoshi Hirazawa: "Depressed cytotoxic activity of hepatic nonparenchymal cells in rats with obstructive jaundice." Surgery. (in Press).

    • Related Report
      1998 Annual Research Report
  • [Publications] 岡 正朗: "膵液漏出を膵瘻とするために" 臨床外科. 52巻. 441-444 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] M Oka: "New Techique for Inducing Reversible Obstructive Jaundice in the Rat" European Surgical Research. 29. 195-201 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] M Oka: "Effect of Intraoperative radiotherapy for pancreatic cancer" Hepato-Biliary-Pancreatic Surgery. (発表予定). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] 岡 正朗: "膵癌の集学的治療" 日本医事新報. 3790号. 6-10 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 岡 正朗: "膵癌の集学的治療" 日本消化器外科学会雑誌. 29(8). 1851-1855 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 正木裕児: "膵癌に対する養子免疫療法" 癌と化学療法. 23(12). 1679-1680 (1996)

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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