Pancreatic cancer immunotherapy using tumor lysate vaccine, engineered to express α-gal epitopes, can target pancreatic cancer stem cells

2012 Fiscal Year Final Research Report

• Project/Area Number: 22591520
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: 国立病院機構呉医療センター (2012); Department of Clinical Research, National Hospital Organization Kure Medical Center (2011); Osaka University (2010)
• Principal Investigator: TANRMURA Masahiro 国立病院機構呉医療センター, 中国がんセンター, 外科医長 (30379250)
• Co-Investigator(Kenkyū-buntansha): DOKI Yuichirou 大阪大学, 医学系研究科, 教授 (20291445) ; MIYOSHI Eiji 大阪大学, 医学系研究科, 教授 (20322183)
• Project Period (FY): 2010 – 2012
• Keywords: 膵癌 / 免疫療法 / 癌幹細胞 / 糖鎖 / 創薬

Research Abstract

The results of our in vitro and in vivo experiments emphasize the efficiency of tumor lysate vaccines expressing α-gal epitopes in targeting all pancreatic cancer cells, including differentiated cancer cells and pancreatic CSCs. Vaccination with α-gal tumor lysate induced strong long-lasting anti-tumor immunity. The α-gal tumor lysate vaccine may form the basis for testing this novel therapeutic approach in human clinical trials.

Research Products

• [Journal Article] Hepatectomy based on the tumor hemodynamics for hepatocellular carcinoma: a comparison among the hybrid and pure laparoscopic procedures and open surgery. (2013)
  • Author(s): Kobayashi S, Nagano H, Marubashi S, Kawamoto K, Wada H, Eguchi H, Tanemura M, Umeshita K, Doki Y, Mori M
  • Journal Title: SurgEndosc Volume: 27 (2) Pages: 610-7
• [Journal Article] Significant Improvement in Islet Yield and Survival with Modified ET-Kyoto Solution (ET-Kyoto/Neutrophil Elastase Inhibitor). (2013)
  • Author(s): Machida T, Tanemura M, Ohmura Y, Tanida T, Wada H, Kobayashi S, Marubashi S, H Eguchi , Ito T, Nagano H, Mori M, Doki Y, Sawa Y
  • Journal Title: Cell Transplant Volume: 22 (1) Pages: 159-73
• [Journal Article] Role of α-gal epitope/anti-Gal antibody reaction in immunotherapy and its clinicalapplication in pancreatic cancer. (2013)
  • Author(s): Tanemura M, Miyoshi, Nagano H, Eguchi H,Taniyama K, Kamiike W, Mori M, Doki Y
  • Journal Title: Cancer Science Volume: 104 (3) Pages: 282-90
• [Journal Article] Clinicopathological features of long-term survivors for advanced biliary tract cancer and impact of the number of lymph nodes involved. (2013)
  • Author(s): Kobayashi S, Nagano H, Marubashi S, Kawamoto K, Wada H, Eguchi H, Tanemura M, Umeshita K, Doki Y, Mori M
  • Journal Title: Int J Surg. Volume: 11 (2) Pages: 145-51
• [Journal Article] IntragraftTranscriptome Level of CXCL9 as Biomarker of Acute Cellular Rejection after Liver Transplantation. (2012)
  • Author(s): AsaokaT, Marubashi S, Kobayashi S, Hama N, Eguchi H, Takeda Y, Tanemura M, Wada H, Takemasa I, Takahashi H, Ruiz P, Doki Y, Mori M, Nagano H
  • Journal Title: J SurgRes Volume: (Epub ahead of print)
• [Journal Article] Arterial Stimulation and Venous Sampling for Glucagonomas of the Pancreas. (2012)
  • Author(s): Eguchi H, Tanemura M, Marubashi S, Kobayashi S, Wada H, Okita K, Iwahashi H, Imagawa A, Shimomura I, Osuga K, Umeshita K, Wakasa K, Mori M, Doki Y, Nagano H
  • Journal Title: Hepatogastroenterology Volume: 59(113) Pages: 276-9
• [Journal Article] Significance of Alanine Aminopeptidase N (APN) in Bile in the Diagnosis of Acute Cellular Rejection After Liver Transplantation. (2012)
  • Author(s): Kim C, Aono S, Marubashi S, Wada H, Kobayashi S, Eguchi H, Takeda Y, Tanemura M,Okumura N, Takao T, Doki Y, Mori M, Nagano H
  • Journal Title: J Surg Res Volume: 175(1) Pages: 138-48
• [Journal Article] Role of Rapamycin induced autophagy in pancreatic islets. (2012)
  • Author(s): Tanemura M, Nagano H, Taniyama K, Kamiike W, Mori M, Doki Y
  • Journal Title: Am J Transplant Volume: 12(4) Pages: 1067
• [Journal Article] Equivalent outcomes after anatomical and non-anatomical resection of smallsolitary hepatocellular carcinoma in patients with preserved liver function. (2012)
  • Author(s): Tomimaru Y, Eguchi H, Marubashi S, WadaH, Kobayashi S, Tanemura M, Umeshita K, Doki Y, Mori M,Nagano H
  • Journal Title: Digest Dis Sci Volume: 57(7) Pages: 1942-8
• [Journal Article] PLOD2 induced under hypoxia is a novel prognostic factor for hepatocellular carcinoma after curative resection. (2012)
  • Author(s): Noda T, Yamamoto H, Takemasa I, Yamada D, Uemura M, Wada H, Kobayashi S, Marubashi S, Eguchi H, Tanemura M, Umeshita K, Doki Y, Mori M, Nagano H
  • Journal Title: Liver Int. Volume: 32 (1) Pages: 110-8
• [Journal Article] Xenon-Inhalation Computed Tomography for Noninvasive Quantitative Measurement of Tissue Blood Flow in Pancreatic Tumor. (2012)
  • Author(s): Kubota M, Murakami T, Nagano H, Eguchi H, Marubashi S, Kobayashi S, Wada H, Tanemura M, Dono K, Nakamori S, Sakon M, Monden M, Mori M, Doki Y
  • Journal Title: Dig Dis Sci. Volume: 57(3) Pages: 801-5
• [Journal Article] Rapamycin causes upregulation of autophagy and impairs islets function both in vitro and in vivo. (2012)
  • Author(s): Tanemura M, Ohmura Y, Deguchi T, Machida T, Tsukamoto R, Wada H, Kobayashi S, Marubashi S, Eguchi H, Ito T, Nagano H, Mori M, Doki Y
  • Journal Title: Am J Transplant. Volume: 12(1) Pages: 102-14
• [Journal Article] Fibrin Sealant with PGA felt for Prevention of Bile Leakage after Liver Resection (2012)
  • Author(s): Kobayashi S, Nagano H, Marubashi S, Wada H, Eguchi H, Takeda Y,Tanemura M, And YD
  • Journal Title: Hepatogastroenterology. Volume: 59 (120) Pages: 2564-8
• [Journal Article] Diagnostic value of FDG-PET for lymp node metastasis and outcome ofsurgery for biliary cancer (2011)
  • Author(s): Kobayashi S, Nagano H, Hoshino H, Wada H, Marubashi S, Eguchi H,Takeda Y, Tanemura M, Kim T, Shimosegawa E, Hatazawa J, Doki Y, Mori M
  • Journal Title: J SurgOncol Volume: 103(3) Pages: 223-9
• [Journal Article] Prognosis of hepatocellular carcinoma with biliary tumor thrombi following liver surgery (2011)
  • Author(s): Noda T, Nagano H, Tomimaru Y, Murakami M, Wada H, Kobayashi S, Marubashi S, Eguchi H, Takeda Y, Tanemura M, Umeshita K, Kim T, Wakasa K, Doki Y, Mori M
  • Journal Title: Surgery Volume: 49(3) Pages: 371-7
• [Journal Article] Tyrosine kinase inhibitor PTK/ZK enhances the anti-tumor effects of interferon-α/5-fluorouracil therapy for hepatocellularcarcinoma cells. (2011)
  • Author(s): Murakami M, Kobayashi S, Marubashi S, Tomimaru Y, Noda T, Wada H,Eguchi H, Takeda Y, Tanemura M, Umeshita K, Doki Y, Mori M, HiroakiNagano H
  • Journal Title: Ann SurgOncol Volume: 18(2) Pages: 589-96
• [Journal Article] A thick pancreas is a risk factor for pancreatic fistula after a distal pancreatectomy:Selection of the closure technique according to the thickness. (2011)
  • Author(s): Eguchi H, Nagano H, Tanemura M, Takeda Y, Marubashi S, Kobayashi S, Wada H, Umeshita K, Mori M, Doki Y
  • Journal Title: Dig Surg Volume: 28(1) Pages: 50-6
• [Journal Article] Clinical Significance of Alpha-Fetoprotein mRNA in Peripheral Blood in Liver Resection for Hepatocellular Carcinoma (2011)
  • Author(s): Marubashi S, Nagano H, Wada H, Kobayashi S, Eguchi H, Takeda Y, Tanemura M, Umeshita K, Doki Y, Mori M
  • Journal Title: Ann SurgOncol Volume: 18 (8) Pages: 2200-9
• [Journal Article] IGFBP7 downregulation is associated with tumor progression and clinical outcome in hepatocellular carcinoma. (2011)
  • Author(s): Tomimaru Y, Eguchi H, Wada H, Kobayashi S, Marubashi S, Tanemura M, Umeshita K, Kim T, Wakasa K, Doki Y, Mori M, Nagano H
  • Journal Title: Int J Cancer Volume: 15;130(2) Pages: 319-27
• [Journal Article] Donor Hepatectomy for Living Donor Liver Transplantation: Learning Steps and Surgical Outcome. (2011)
  • Author(s): Marubashi S, Nagano H, Wada H, Kobayashi S, Eguchi H, Takeda Y,Tanemura M, Doki Y, Mori M.
  • Journal Title: Dig Dis Sci Volume: 56 (8) Pages: 2482-90
• [Journal Article] Synergistic antitumor effect of interferon-β with gemcitabine in interferon-α-non-responsive pancreatic cancer cells. (2011)
  • Author(s): Tomimaru Y, Eguchi H, Wada H, Tomokuni A, Kobayashi S, Marubashi S, Takeda Y, Tanemura M, Umeshita K, Mori M, Doki Y, Nagano H
  • Journal Title: Int J Oncol Volume: 38(5) Pages: 1237-43
• [Journal Article] Mural nodule in branch duct-type intraductal papillary mucinous neoplasms of the pancreas is a marker of malignant transformation and indication for surgery. (2011)
  • Author(s): Akita H, Takeda Y, Hoshino H, Wada H, Kobayashi S, Marubashi S, Eguchi H, Tanemura M, Mori M, Doki Y, Nagano H
  • Journal Title: Am J Surg Volume: 202 (2) Pages: 214-9
• [Journal Article] Combination use of anti-CD133 antibody and SSA lectin can effectively enrich cells with high tumorigenicity. (2011)
  • Author(s): Moriwaki K, Okudo K, Haraguchi N, Takeishi S, Sawaki H, Narimatsu H, Tanemura M, Ishii H, Mori M, Miyoshi E
  • Journal Title: Cancer Sci Volume: 102 (6) Pages: 1164-70
• [Journal Article] Ep-CAM is a significant prognostic factor in pancreatic cancer patients by suppressing cell activity. (2011)
  • Author(s): Akita H, Nagano H, Takeda Y, Eguchi H, Wada H, Kobayashi S, Marubashi S, Tanemura M, Takahashi H, Ohigashi H, Tomita Y, Ishikawa O, Mori M, Doki Y
  • Journal Title: Oncogene Volume: 4; 30 (31) Pages: 3468-76
• [Journal Article] Successful pregnancy after simultaneous pancreas-kidney transplantation from a brain-dead donor: the first case report in Japan. (2011)
  • Author(s): Koyama S, Tomimatsu T, Kanagawa T, Daimon E, Kimura T, Kuroda A,Tanemura M, Doki Y, Ito T
  • Journal Title: J Obstetrics Gynaecol Res Volume: 37 (11) Pages: 1711-6
• [Journal Article] Long-term outcome of combined subcutaneous interferon-αand intra-arterial 5-fluorouracil treatment for advanced hepatocellular carcinoma with major portal vein thrombosis. (2011)
  • Author(s): Nagano H, Wada H, Kobayashi S, Marubashi S, Eguchi H, Tanemura M, Tomimaru Y, Osuga K, Umeshita K, Doki Y, Mori M
  • Journal Title: Oncology Volume: 80 (1-2) Pages: 63-9
• [Journal Article] Circulating microRNA-21 as a novel biomarker for hepatocellular carcinoma. (2011)
  • Author(s): Tomimaru Y, Eguchi H, Nagano H, Wada H, Kobayashi S, Marubashi S,Tanemura M, Tomokuni A, Takemasa I, Umeshita K, Kanto T, Doki Y, Mori M
  • Journal Title: J Hepatol Volume: 56 (1) Pages: 167-75
• [Journal Article] Significance of Alanine Aminopeptidase N (APN) in Bile in the Diagnosis of Acute Cellular Rejection After Liver Transplantation. (2011)
  • Author(s): Kim C, Aono S, Marubashi S, Wada H, Kobayashi S, Eguchi H, Takeda Y, Tanemura M, Okumura N, Takao T, Doki Y, Mori M, Nagano H
  • Journal Title: J Surg Res Volume: (Epub ahead of print)
• [Journal Article] Treatment of borderline cases for curative resection of biliary tract cancer. (2011)
  • Author(s): Kobayashi S, Nagano H, Marubashi S, Wada H, Eguchi H, Takeda Y, Tanemura M, Umeshita K, Doki Y, Mori M
  • Journal Title: J SurgOncol Volume: 104 (5) Pages: 499-503
• [Journal Article] Reprogramming of mouse and human cells to pluripotency using mature microRNAs. (2011)
  • Author(s): Miyoshi N, Ishii H, Tanemura M, Sekimoto M, Doki Y, Mori M
  • Journal Title: Cell Stem Cell Volume: 3; 8 (6) Pages: 633-8
• [Journal Article] Experience with the use of fibrin sealant plus polyglycolic acid felt at the cut surface of the liverinlaparoscopic hepatectomy. (2011)
  • Author(s): Kobayashi S, Nagano H, Marubashi S, Wada H, Takeda Y, Eguchi H, Tanemura M, Umeshita K, Doki Y, Mori M
  • Journal Title: SurgEndosc Volume: 25 (11) Pages: 3590-6
• [Journal Article] Successful adult ABO incompatible living donor liver transplantation: experience with double infusion through the hepatic artery and portal vein. (2011)
  • Author(s): Kobayashi S, Nagano H, Marubashi S, Wada H, Takeda Y, Eguchi H, Tanemura M, Umeshita K, Doki Y, Mori M
  • Journal Title: Hepatogastroenterology Volume: 58(106) Pages: 503-7
• [Journal Article] Role of the Hypoxia-Related Gene, JMJD1A, in Hepatocellular Carcinoma: Clinical Impact on Recurrence after Hepatic Resection. (2011)
  • Author(s): Yamada D, Kobayashi S, Yamamoto H, Tomimaru Y, Noda T, Uemura M, Wada H, Marubashi S, Eguchi H,Tanemura M, Doki Y, Mori M, Nagano H
  • Journal Title: Ann SurgOncol Volume: (Epub ahead of print)
• [Journal Article] Increased immunogenicity of tumor-associated antigen, MUC1, engineered to express α-gal epitopes: A novel approach to immunotherapy in pancreatic cancer (2010)
  • Author(s): Deguchi T, Tanemura M, Miyoshi E, Nagano H, Machida T, Ohmura Y, Kobayashi S, Marubashi S, Eguchi H, Takeda Y, Ito T, Mori M, Doki Y and Sawa Y
  • Journal Title: Cancer Research Volume: 70 (13) Pages: 5259-69
• [Journal Article] Effects of preceding interferon therapy on outcome after surgery for hepatitis C virus-related hepatocellular carcinoma (2010)
  • Author(s): Tomimaru Y, Nagano H, Eguchi H, Kobayashi S, Marubashi S, Wada H, Tanemura M, Umeshita K, Hiramatsu N, Takehara T, Doki Y, Mori M
  • Journal Title: J of Surg Oncol Volume: 15;102(4) Pages: 308-14
• [Journal Article] MicroRNA-21 induces resistance to the anti-tumour effect of interferon-α/5-fluorouracil in hepatocellular carcinoma cells (2010)
  • Author(s): Tomimaru Y, Eguchi H, Nagano H, Wada H, Tomokuni A, Kobayashi S, Marubashi S, Takeda Y, Tanemura M, Umeshita K, Doki Y, Mori M
  • Journal Title: Br J Cancer Volume: 9;103(10) Pages: 1617-26
• [Journal Article] Combined Transplantation of Pancreatic Islets and Adipose Tissue-Derived Stem Cells Enhances the Survival and Insulin Function ofIslet Grafts in Diabetic Mice (2010)
  • Author(s): Ohmura Y, Tanemura M, Kawaguchi N, Machida T, Tanida T, Deguchi T, Wada H, Kobayashi S, Marubashi S, Eguchi H, Takeda Y, Matsuura N, Ito T, Nagano H, Doki Y and Mori M
  • Journal Title: Transplantation Volume: 27;90(12) Pages: 1366-73
• [Presentation] A novel immunotherapy for pancreatic cancer stem cells by tumor lysate vaccine, expressing α-gal epitopes (2012)
  • Author(s): Masahiro Tanemura
  • Organizer: Pancreas Cancer 2012 in Kyoto
  • Place of Presentation: 京都
  • Year and Date: 20121000
• [Presentation] A new immunotherapy for pancreatic cancer stem cells by tumor lysate vaccine, expressing α-gal epitopes (2012)
  • Author(s): Masahiro Tanemura
  • Organizer: AACR総会
  • Place of Presentation: シカゴ
  • Year and Date: 20120400
• [Presentation] Immune-based therapy with tumor lysate, remodeled to express α-gal epitopes induce significant B and T cell responses against pancreatic cancer. (2012)
  • Author(s): Masahiro Tanemura
  • Organizer: AACR総会
  • Place of Presentation: シカゴ
  • Year and Date: 20120400
• [Presentation] Vaccination with pancreatic cancer cells expressing α-gal epitopes effectively induced immuneresponses against not only differentiated cancer cells but also cancer stem cells (2011)
  • Author(s): Masahiro Tanemura
  • Organizer: AACR総会
  • Place of Presentation: フロリダ
  • Year and Date: 20110400
• [Presentation] Preliminary experiment of α-gal epitopes immune-based therapy against pancreatic cancer, by tumor cell lysates (2011)
  • Author(s): Masahiro Tanemura
  • Organizer: AACR総会
  • Place of Presentation: フロリダ
  • Year and Date: 20110400
• [Presentation] MUC1, remodeled to express α-gal epitopes immune-based therapy can elicit both significant prolonged survival and effective antibody production against multiple tumor-associated antigens (2010)
  • Author(s): Tanemura M, Deguchi T, Miyoshi E, Nagano H, Ohmura Y, Machida T, Wada H, Kobayashi S, Marubash S, Eguchi H, Takeda Y, Ito T, Mori M and Doki Y
  • Organizer: AACR 101nd Annual Meeting
  • Place of Presentation: ワシントン
  • Year and Date: 20100400
• [Book] レジデントのための消化器外科診療マニュアル (2012)
  • Author(s): 種村匡弘
  • Total Pages: 459
  • Publisher: 医学書院
• [Patent(Industrial Property Rights)] 膵島の分離方法および膵島組織を保護するための保護液 (2010)
  • Inventor(s): 種村匡弘
  • Industrial Property Rights Holder: 大塚製薬工場
  • Industrial Property Number: 特願2010-159053
  • Filing Date: 2010-07-13
  • Overseas
• [Patent(Industrial Property Rights)] 膵島と脂肪組織由来幹細胞を利用した膵島移植 (2010)
  • Inventor(s): 種村匡弘
  • Industrial Property Rights Holder: 大阪大学
  • Industrial Property Number: 特願2010-177993
  • Filing Date: 2010-08-06
  • Overseas