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Immunotherapy for prevention of postoperative recurrence in pancreatic cancer using cell therapy and vaccine therapy

Research Project

Project/Area Number 15390397
Research Category

Grant-in-Aid for Scientific Research (B)

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, Hospital, Assistant Professor, 医学部附属病院, 講師 (50253159)
YOSHINO Shigefumi  Yamaguchi University, Faculty of Medicine, Assistant, 医学部, 講師 (60294633)
YAMAMOTO Kotaro  Yamaguchi University, Faculty 1 of Medicine, Researcher, 医学部, 非常勤研究員 (50304481)
IIZUKA Norio  Yamaguchi University, Faculty 1 of Medicine, Research Associate, 医学部, 助手 (80332807)
Project Period (FY) 2003 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥14,500,000 (Direct Cost: ¥14,500,000)
Fiscal Year 2005: ¥4,200,000 (Direct Cost: ¥4,200,000)
Fiscal Year 2004: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2003: ¥6,300,000 (Direct Cost: ¥6,300,000)
KeywordsPancreatic Cancer / cell therapy / vaccine therapy / postoperative recurrence / 手術 / 予後 / 遺伝子解析 / 樹状細胞 / CTL療法 / マイクロアレイ
Research Abstract

(1)Thirty patients with pancreatic cancer were treated by immunotherapy using MUC1-CTL after curative resection. Only 3 patient (10%) had liver recurrence. However, 19 patients (63%) had local recurrence. One year, 2 year, and 3 year survival rate were 83.3%, 32.4%, and 19.9%, respectively. This immunotherapy may prevent liver metastasis after surgery, but can not control local recurrence.
(2)To evaluate safety and immunological responses, we conducted a phase I study of personalized peptide vaccination for pancreatic cancer patients (n=11). Namely, pre-vaccination peripheral blood mononuclear cells were screened for their reactivity in vitro to each of 14 or 16 peptides in HLA-A24(+) or -A2(+) patients, and only the reactive peptides (maximum:4) were vaccinated in vivo. This regimen was generally well tolerated, although inflammatory reactions at the injection site were observed in 7 patients. Delayed-type hypersensitivity to peptides used for vaccination was observed in 7 patients. Increased cellular and humoral immune responses to at least one of peptides used for vaccination were observed in the post-vaccination PBMCs and sera from 4 of 8 patients and 4 of 10 patients tested, respectively. The 6- and 12-month survival rates for patients who received >3 vaccinations (n=10) were 80% and 20%, respectively. Due to tolerability and capability of inducing specific immunity, further development of personalized peptide-based immunotherapy for pancreatic cancer patients is warranted.
(3)We performed MUC1-CTL+personalized peptide-based immunotherapy in 3 patients undergone curative resection for pancreatic cancer. All patients still alive without recurrence.
(4)Fifteen patients with unresectable or recurrence pancreatic cancer were treated with MUC1-CTL+MUC1 peptide stimulated dendritic cells (DC) therapy. One patients had CR and 4 patients had SD. No severe side effects was observed.

Report

(4 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • Research Products

    (43 results)

All 2005 2004 2003 Other

All Journal Article (35 results) Book (3 results) Publications (5 results)

  • [Journal Article] MUC1 peptide vaccination in patients with advanced pancreas or biliary tract cancer.2005

    • Author(s)
      Yamamoto K
    • Journal Title

      Anticancer Research 25(5)

      Pages: 3575-3579

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Current Antibiotic prophylaxis in pancreatodudenectomy in Japan.2005

    • Author(s)
      Ueno T
    • Journal Title

      JHBP Surgery 12(4)

      Pages: 304-309

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Immunological evaluation of personalized peptide vzccination for patients with pancreatic cancer.2005

    • Author(s)
      Yamamoto K
    • Journal Title

      Oncology Report 13(5)

      Pages: 874-883

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 術後膵瘻2005

    • Author(s)
      上野富雄
    • Journal Title

      手術 59(10)

      Pages: 1512-1520

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 非特異的免疫療法2005

    • Author(s)
      吉野茂文
    • Journal Title

      Biotherapy 19(2)

      Pages: 143-150

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 全胃幽門輪温存膵頭十二指腸切除術2005

    • Author(s)
      岡正朗
    • Journal Title

      消化器外科 28(1)

      Pages: 1-13

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] MUC1 peptide vacccination in patients with advanced pancreas or biliary tract cancer.2005

    • Author(s)
      Yamamoto K, et al.
    • Journal Title

      Anticancer Res. 25(5)

      Pages: 3575-3579

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Current Antibiotic Prophylaxis in Pancreatodudenectomy in Japan.2005

    • Author(s)
      Ueno T, et al.
    • Journal Title

      JHBP Surgery 12(4)

      Pages: 304-309

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Immunological evaluation of personalized peptide vaccination for patients with pancreatic cancer.2005

    • Author(s)
      Yamamoto T, et al.
    • Journal Title

      Oncol Rep. 13(5)

      Pages: 874-883

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Pancreatic fistel after pancreatectomy2005

    • Author(s)
      Ueno T, et al.
    • Journal Title

      Syujyutu 59(10)

      Pages: 1512-1520

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Nonspecific Cancer immunotherapy2005

    • Author(s)
      Yoshino S, et al.
    • Journal Title

      Biotherapy 19(2)

      Pages: 143-150

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Pylorus preserving pancreaticoduodenectomy.2005

    • Author(s)
      Oka M, et al.
    • Journal Title

      Syoukakigeka 28(1)

      Pages: 1-13

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Cancer Immunotherapy2005

    • Author(s)
      Hazama S, et al.
    • Journal Title

      Review of Digestive Surgery

      Pages: 249-249

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Cell therapy for pancreatic cancer.2005

    • Author(s)
      Nagashima Y, et al.
    • Journal Title

      Chemo-Immunotherapy for Cancer

      Pages: 227-227

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] MUC1 peptide vaccination in patients with advanced pancreas or biliary tract cancer.2005

    • Author(s)
      Yamamoto K, Oka M, et al.
    • Journal Title

      Anticancer Research 25・5

      Pages: 3575-3579

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Immunological evaluation of personalized peptide vaccination for patients with pancreatic cancer.2005

    • Author(s)
      Yamamoto K, Oka M, et al.
    • Journal Title

      Oncology Report 13・5

      Pages: 874-883

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Current Antibiotic Prophylaxis in Pancreatodudenectomy in Japan.2005

    • Author(s)
      Ueno T, Oka M, et al.
    • Journal Title

      Journal of Hepato-Biliary-Pancreatic Surgery 12・4

      Pages: 304-309

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 術後膵瘻2005

    • Author(s)
      上野富雄, 岡 正朗, 他
    • Journal Title

      手術 59(10)

      Pages: 1512-1520

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 全胃幽門輪温存温存膵頭十二指腸切除術2005

    • Author(s)
      岡 正朗
    • Journal Title

      消化器外科 28(1)

      Pages: 1-13

    • Related Report
      2004 Annual Research Report
  • [Journal Article] CIITA methylation and decreased levels of HLA-DR in tumour progression.2004

    • Author(s)
      Iizuka N
    • Journal Title

      British journal of Cancer 91(4)

      Pages: 814-815

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Tumor secreting high levels of IL-15 induce specific immunity through CD8+ cells to low immunogeneic colon adenocarcinoma.2004

    • Author(s)
      Araki A
    • Journal Title

      International Journal of Molecular Medicine 14(1)

      Pages: 571-576

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 〔外科治療選択のタイミング〕 重症急性膵炎2004

    • Author(s)
      上野富雄
    • Journal Title

      臨床外科 60(1)

      Pages: 55-60

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] CIITA methylation and decreased levels of HLA-DR in tumour progression.2004

    • Author(s)
      Iizuka N, et al.
    • Journal Title

      Brit J cancer. 91(4)

      Pages: 814-815

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Tumor secreting high levels of IL-15 induces specific immunity through CD8+ T cells to low immunogeneic colon adenocarcinoma.2004

    • Author(s)
      Araki A, et al.
    • Journal Title

      Int J Mol Med. 14(1)

      Pages: 571-576

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Therapy for severe acute pancreatitis.2004

    • Author(s)
      Ueno T, et al.
    • Journal Title

      Rinsyogeka 60(1)

      Pages: 55-60

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 消化器癌のワクチン療法2004

    • Author(s)
      岡 正朗
    • Journal Title

      山口医学 52(3)

      Pages: 1-8

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Increased expression of MUC1 in advanced pancreatic cancer.2003

    • Author(s)
      Hinoda Y
    • Journal Title

      Journal of Gastroenterology 38(12)

      Pages: 1162-1166

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 膵頭十二指腸切除術後の再建法とその意義2003

    • Author(s)
      山本光太郎
    • Journal Title

      消化器外科 26(12)

      Pages: 1779-1786

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 消化器癌のワクチン療法2003

    • Author(s)
      岡正朗
    • Journal Title

      山口医学 52(3)

      Pages: 52-54

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Increased expression of MUC1 in advanced pancreatic cancer.2003

    • Author(s)
      Hinoda Y, et al.
    • Journal Title

      J Gastroenterol 38(12)

      Pages: 1162-1166

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Reconstruction after pancreaticoduodenectomy.2003

    • Author(s)
      Yamamoto K, et al.
    • Journal Title

      Syoukakigeka 26(12)

      Pages: 1779-1786

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Vaccine therapy for digestive malignancy2003

    • Author(s)
      Oka M.
    • Journal Title

      Yamaguchi-Igaku 52(3)

      Pages: 52-54

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Immunological evaluation of personalized peptide vaccination for patients with pancreatic cancer.

    • Author(s)
      Yamamoto K, Oka M, et al.
    • Journal Title

      Oncol Rep (In press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Adoptive immunotherapy for pancreatic cancer using cytotoxic T-lymphocytes stimulated by a MUC1-expressed human pancreatic cancer

    • Author(s)
      Kawaoka T, Oka M, et al.
    • Journal Title

      Ann Surg (In press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] MUC1 peptide vaccination in patients with advanced pancreatic or biliary tract cancer.

    • Author(s)
      Yamamoto K, Oka M, et al.
    • Journal Title

      Hepato-Gastroenterology (In press)

    • Related Report
      2004 Annual Research Report
  • [Book] 消化器外科レビュー20052005

    • Author(s)
      硲 彰一
    • Total Pages
      249
    • Publisher
      株式会社総合医学社
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] これだけは知っておきたい癌の免疫化学療法2005

    • Author(s)
      長島由紀子
    • Total Pages
      227
    • Publisher
      株式会社総合医薬ジャーナル社
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] 癌の免疫化学療法-膵癌における治療方法とその成績2005

    • Author(s)
      長島由紀子, 岡 正朗, 他
    • Publisher
      総合医学社
    • Related Report
      2005 Annual Research Report
  • [Publications] Suzuki N, Tanaka S, Maeda Y, Oka M, et al.: "Vaccine therapy using peptide for HLA-02 or HLA-24 patients with advanced pancreatic cancer"Int J Cancer. (In press).

    • Related Report
      2003 Annual Research Report
  • [Publications] Yamamoto K, Oka M.: "MUC1 peptide therapy for advanced pancreatic cancer"Jpn J Cancer Res. (In press).

    • Related Report
      2003 Annual Research Report
  • [Publications] Kawaoka T, Oka M, Hazama S.: "Combination immunotherapy using MUC1 stimulated cytotoxic T cells and dendritic cells for advanced pancreatic cancer"Surgery. (In press).

    • Related Report
      2003 Annual Research Report
  • [Publications] Hinoda Y, Oka M, et al.: "Increased expression of MUC1 in advanced pancreatic cancer"J Gastroenterol. 38. 1162-1166 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Iizuka N, Oka M, et al.: "Use of oligonucleotide microarray as a novel approach for prediction of early intrahepatic recurrence in hepatocellular carcinoma after curative resection"Lancet. 361(9361). 923-929 (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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