Two types of monoclonal antibodies generated by immunizing mice with MIA-PaCa-2 human pancreatic cancer cell line for diagnostic and therapeutic strategies for pancreatic cancer

• Project/Area Number: 16K10595
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Shimane University
• Principal Investigator: Tajima Yoshitsugu 島根大学, 学術研究院医学・看護学系, 教授 (20264228)
• Co-Investigator(Kenkyū-buntansha): 浦野 健 島根大学, 学術研究院医学・看護学系, 教授 (70293701) ; 西 健 島根大学, 学術研究院医学・看護学系, 助教 (80538893)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: モノクローナル抗体 / 膵がん / 早期診断 / 治療法 / がん表面抗原 / バイオ医薬品開発

Outline of Final Research Achievements

Two types of monoclonal antibodies were generated by immunizing mice with MIA-PaCa-2 human pancreatic cancer cell line. Mass spectrometry analysis revealed that mAb 4-6.8 recognizes human epidermal growth factor receptor (EGFR). Protein array analysis and CRISPR/Cas9 system showed that mAb 12-13.8 recognizes a cell membrane glycoprotein. mAb 12-13.8 stained the cell membrane of cancer cells and increased 12-13.8-positive staining worsened the prognosis of lung and pancreatic cancer patients using immunohistochemistry. in vivo imaging system (IVIS) elucidated that mAb 12-13.8 labeled with indocyanine green (ICG) was concentrated at palpable tumors of MIA-PaCa-2 cells implanted subcutaneously in nu/nu mice. And Liposome-based cancer drug delivery system with mAb 12-13.8 as an active targeting ligand markedly suppresses the growth of MIA-PaCa-2 cells implanted subcutaneously in nu/nu mice.
The mAb 12-13.8 will be very useful for diagnostic and therapeutic strategies for pancreatic cancer.

Academic Significance and Societal Importance of the Research Achievements

ヒト膵がん細胞株MIA PaCa-2を免疫源として樹立した、がん細胞表面を認識するマウスモノクローナル抗体12-13.8はその染色強度は肺がんおよび膵がん患者の予後と相関しており、同抗体修飾抗腫瘍薬内包リポソームを用いた治療実験により腫瘍増殖抑制効果を有することを確認した。12-13.8はがんの早期診断・予後診断、さらにバイオ医薬品開発の重要なシーズとなる。

Research Products

• [Journal Article] A Case of Left Ventricular Thrombus with Superior Mesenteric Vein Thrombosis Due to Atopic Dermatitis (2018)
  • Author(s): Ito S, Endo A, Okada T, Yoshitomi H, Hyakudomi R, Tajima Y, Tanabe K.
  • Journal Title: International Heart Journal Volume: 59 Issue: 4 Pages: 881-886
  • DOI: 10.1536/ihj.17-386
  • NAID: 130007428322
  • ISSN: 1349-2365, 1349-3299
  • Year and Date: 2018-07-31
  • Peer Reviewed / Open Access
• [Journal Article] Antidiabetic adiponectin receptor agonist AdipoRon suppresses tumour growth of pancreatic cancer by inducing RIPK1/ERK-dependent necroptosis (2018)
  • Author(s): 17.Akimoto M, Maruyama R, Kawabata Y, Tajima Y, Takenaga K.
  • Journal Title: Cell Death & Disease Volume: 9 Issue: 8 Pages: 804-804
  • DOI: 10.1038/s41419-018-0851-z
  • Peer Reviewed / Open Access
• [Journal Article] Prognostic significance of red cell distribution width in esophageal squamous cell carcinoma. (2018)
  • Author(s): Hirahara N, Tajima Y, Fujii Y, Hyakudomi R, Yamamoto T, Ishitobi K, Taniura T, Kawabata Y.
  • Journal Title: Journal of Surgical Research Volume: 230 Pages: 53-60
  • DOI: 10.1016/j.jss.2018.04.051
  • Peer Reviewed
• [Journal Article] Preoperative Prognostic Nutritional Index Predicts Long-term Outcome in Gastric Cancer: A Propensity Score-matched Analysis. (2018)
  • Author(s): Hirahara N, Tajima Y, Fujii Y, Yamamoto T, Hyakudomi R, Taniura T, Kaji S, Kawabata Y.
  • Journal Title: Anticancer Research Volume: 38 Issue: 8 Pages: 4735-4746
  • DOI: 10.21873/anticanres.12781
  • Peer Reviewed
• [Journal Article] Complete abdominal wound and anastomotic leak with diffuse peritonitis closure achieved by an abdominal vacuum sealing drainage in a critical ill patient: a case report. (2018)
  • Author(s): Fujii Y, Tajima Y, Kaji S, Kishi T, Miyazaki Y, Taniura T, Hirahara N.
  • Journal Title: BMC Surgery Volume: 18 Issue: 1 Pages: 41-41
  • DOI: 10.1186/s12893-018-0375-6
  • Peer Reviewed / Open Access
• [Journal Article] Carney complex: a case with thyroid follicular adenoma without a PRKAR1A mutation. (2018)
  • Author(s): Hattori S, Yamane Y, Shimomura R, Uchida Y, Toyota N, Miura Y, Shiota S, Tajima Y.
  • Journal Title: Surgical Case Reports Volume: 4 Issue: 1 Pages: 34-34
  • DOI: 10.1186/s40792-018-0438-z
  • Peer Reviewed / Open Access
• [Journal Article] Preoperative imaging evaluation of pancreatic pathologies for objective prediction of pancreatic fistula after pancreaticoduodenectomy (2018)
  • Author(s): Tajima Y, Kawabata Y, Hirahara N.
  • Journal Title: Surg Today Volume: 48 Issue: 2 Pages: 140-150
  • DOI: 10.1007/s00595-017-1529-3
  • Peer Reviewed
• [Journal Article] Bevacizumab-induced intestinal perforation in a patient with inoperable breast cancer: a case report and review of the literature. (2018)
  • Author(s): Fujii Y, Hirahara N, Kaji S, Taniura T, Hyakudomi R, Yamamoto T, Tajima Y.
  • Journal Title: J Med Case Rep. Volume: 12 Issue: 1 Pages: 84-84
  • DOI: 10.1186/s13256-018-1619-x
  • Peer Reviewed / Open Access
• [Journal Article] Prognostic nutritional index as a predictor of survival in resectable gastric cancer patients with normal preoperative serum carcinoembryonic antigen levels: a propensity score matching analysis. (2018)
  • Author(s): Hirahara N, Tajima Y, Fujii Y, Kaji S, Yamamoto T, Hyakudomi R, Taniura T, Kawabata Y.
  • Journal Title: BMC Cancer Volume: 18 Issue: 1 Pages: 285-285
  • DOI: 10.1186/s12885-018-4201-4
  • Peer Reviewed / Open Access
• [Journal Article] Case of colonic intussusception secondary to mobile cecum syndrome repaired by laparoscopic cecopexy using a barbed wound suture device. (2018)
  • Author(s): Yamamoto T, Tajima Y, Hyakudomi R, Hirayama T, Taniura T, Ishitobi K, Hirahara N.
  • Journal Title: World J Gastroenterol. Volume: 42 Issue: 1 Pages: 172-184
  • DOI: 10.1007/s00268-017-4144-y
  • Peer Reviewed / Open Access
• [Journal Article] Liver parenchyma transection-first approach in hemihepatectomy with en bloc caudate lobectomy for hilar cholangiocarcinoma: A safe technique to secure favorable surgical outcomes. (2017)
  • Author(s): Kawabata Y, Hayashi H, Yano S, Tajima Y.
  • Journal Title: J Surg Oncol. Volume: 印刷中 Issue: 8 Pages: 963-970
  • DOI: 10.1002/jso.24612
  • Peer Reviewed
• [Journal Article] HMGB1 is a promising therapeutic target for acute liver failure. (2017)
  • Author(s): Yamamoto T, Tajima Y.
  • Journal Title: Expert Rev Gastroenterol Hepatol. Volume: 11 Issue: 7 Pages: 673-682
  • DOI: 10.1080/17474124.2017.1345625
  • Peer Reviewed
• [Journal Article] Prognostic significance of preoperative inflammatory response biomarkers in patients undergoing curative thoracoscopic esophagectomy for esophageal squamous cell carcinoma. (2017)
  • Author(s): Hirahara N, Matsubara T, Kawahara D, Nakada S, Ishibashi S, Tajima Y.
  • Journal Title: Eur J Surg Oncol. Volume: 43 Issue: 2 Pages: 493-501
  • DOI: 10.1016/j.ejso.2016.11.018
  • Peer Reviewed
• [Journal Article] Validation of a novel prognostic scoring system using inflammatory response biomarkers in patients undergoing curative thoracoscopic esophagectomy for esophageal squamous cell carcinoma. (2017)
  • Author(s): Hirahara N, Fujii Y, Yamamoto T, Hyakudomi R, Hirayama T, Taniura T, Ishitobi K, Tajima Y.
  • Journal Title: Onco Targets Ther. Volume: 10 Pages: 363-370
  • DOI: 10.2147/ott.s124556
  • Peer Reviewed / Open Access
• [Journal Article] Prognostic value of preoperative inflammatory response biomarkers in patients with esophageal cancer who undergo a curative thoracoscopic esophagectomy. (2016)
  • Author(s): Hirahara N, Matsubara T, Mizota Y, Ishibashi S, Tajima Y
  • Journal Title: BMC Surg. Volume: 16 Issue: 1 Pages: 66-66
  • DOI: 10.1186/s12893-016-0179-5
  • Peer Reviewed / Open Access
• [Journal Article] Prognostic value of hematological parameters in patients undergoing esophagectomy for esophageal squamous cell carcinoma. (2016)
  • Author(s): Hirahara N, Matsubara T, Kawahara D, Mizota Y, Ishibashi S, Tajima Y
  • Journal Title: Int J Clin Oncol. Volume: 21 Issue: 5 Pages: 909-919
  • DOI: 10.1007/s10147-016-0986-9
  • Peer Reviewed
• [Journal Article] Total meso-pancreatoduodenum excision with pancreaticoduodenectomy in lower biliary tract cancer. (2016)
  • Author(s): Kawabata Y, Hayashi H, Ishikawa N, Tajima Y.
  • Journal Title: Langenbecks Arch Surg. Volume: 401 Issue: 4 Pages: 463-469
  • DOI: 10.1007/s00423-016-1435-y
  • Peer Reviewed
• [Journal Article] Modified total meso-pancreatoduodenum excision with pancreaticoduodenectomy as a mesopancreatic plane surgery in borderline resectable pancreatic cancer. (2016)
  • Author(s): Kawabata Y, Tanaka T, Ishikawa N, Hayashi H, Tajima Y.
  • Journal Title: Eur J Surg Oncol. Volume: 42 Issue: 5 Pages: 698-705
  • DOI: 10.1016/j.ejso.2016.02.241
  • Peer Reviewed
• [Presentation] Risk evaluation and prediction for POPF (2018)
  • Author(s): Tajima Y
  • Organizer: AOPA & KPBA & KPSC 2018
  • Int'l Joint Research
• [Presentation] Efficacy of adjuvant chemoratiation therapy on survival in patients with curative resected pancreatic cancer. (2017)
  • Author(s): Kawabata Yasunari, Hayashi Hikota, Nishi Takeshi, Kishi Takashi, Tajima Yoshitsugu.
  • Organizer: International association of pancreatology/Latin America pancreatic study group Joint Meeting 2017
  • Int'l Joint Research
• [Presentation] Preliminary study on the efficacy of conversion surgery following intensive chemotherapy for initially unresectable pancreatic cancer． (2017)
  • Author(s): Kishi Takashi, Kawabata Yasunari, Nishi Takeshi, Hayashi Hikota, Tajima Yoshitsugu
  • Organizer: International association of pancreatology/Latin America pancreatic study group Joint Meeting 2017
  • Int'l Joint Research
• [Presentation] Assessment of predictive accuracy of postoperative compolication in pancreatic surgery: POSSUM vs E-PASS． (2017)
  • Author(s): Hayashi Hikota, Kawabata Yasunari, Nishi Takeshi, Kishi Takashi, Tajima Yoshitsugu
  • Organizer: International association of pancreatology/Latin America pancreatic study group Joint Meeting 2017
  • Int'l Joint Research
• [Presentation] Radical pancreatectomy with artery-first approach based on tumor-infiltrated site in pancreatic cancer: Surgical technique to obtain complete tumor resection and its outcomes. (2016)
  • Author(s): Yasunari Kawabata, Hikota Hayashi, Yoshitsugu Tajima.
  • Organizer: 26th World congress of the International Association of Surgeons, Gastroenterologists and Oncologists(IASGO 2016).
  • Place of Presentation: Soul (Sheraton Grande Walerhill Hotel)
  • Year and Date: 2016-09-08
  • Int'l Joint Research
• [Presentation] A branch-closing technique to reduce postoperative pancreatic fistula after pancreatectomy. (2016)
  • Author(s): Yasunari Kawabata, Hikota Hayashi, Kazunorii Mizutani, Yoshitsugu Tajima
  • Organizer: 第47回日本膵臓学会/第20回国際膵臓学会/第6回アジアオセアニア膵臓学会
  • Place of Presentation: 仙台（仙台国際センター）
  • Year and Date: 2016-08-04
  • Int'l Joint Research
• [Remarks] 島根大学医学部附属病院消化器・総合外科ホームページ
  • URL: https://www.shimane-u-dgs.jp/
• [Remarks] 島根大学医学部消化器・総合外科
  • URL: http://www.shimane-u-dgs.jp/
• [Remarks] 島根大学医学部附属病院 消化器・総合外科 ホームページ
  • URL: http://www.shimane-u-dgs.jp/