Proteomic screening for pancreatic cancer antigen and development of antibody-based medicine.

• Project/Area Number: 25860575
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Gastroenterology
• Research Institution: National Institutes of Biomedical Innovation, Health and Nutrition
• Principal Investigator: SERADA SATOSHI 国立研究開発法人医薬基盤・健康・栄養研究所, 免疫シグナルプロジェクト, 研究員 (50463302)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 癌 / プロテオーム / タンパク質 / 抗体医薬 / 蛋白質

Outline of Final Research Achievements

By quantitative proteomic approach, cell surface membrane proteins were screened by comparing normal human pancreatic epithelial cells and pancreatic carcinoma cells. Elevated expression levels of the candidate cancer antigen was confirmed by immunohistochemical staining analysis using pancreatic carcinoma tissue sections. We developed novel monoclonal antibody targeting this antigen and found that some clone represented internalization into cells. When in vitro antibody-drug conjugate (ADC) assay was performed using primary antibody and second antibody, which was conjugated with tubulin inhibitor, the value was IC50 was less than 1 nM against antigen positive pancreatic carcinoma cells. We confirmed specific anti-tumor effect of the monoclonal antibody by ADC toward pancreatic carcinoma.

Research Products

• [Journal Article] CpG ODN potentiates the anti-tumor activity of anti-BST2 antibody. (2015)
  • Author(s): Hiramatsu, K., Serada, S., Kobiyama, K., Nakagawa, S., Morimoto, A., Matsuzaki, S., Ueda,Y., Fujimoto, M., Yoshino, K., Ishii, K., Enomoto, T., Kimura, T., Naka, T.
  • Journal Title: Cancer Science Volume: 106(10) Issue: 10 Pages: 474-82
  • DOI: 10.1111/cas.12738
  • Peer Reviewed / Open Access
• [Journal Article] Suppressor of cytokine signalling-1 induces significant preclinical antitumor effect in malignant melanoma cells. (2015)
  • Author(s): Tagami-Nagata N, Serada S, Fujimoto M, Tanemura A, Nakatsuka R, Ohkawara T, Murota H, Kishimoto T, Katayama I, Naka T.
  • Journal Title: Exp Dermatol. Volume: 24 Issue: 11 Pages: 864-71
  • DOI: 10.1111/exd.12802
  • Peer Reviewed
• [Journal Article] Gene therapy with SOCS1 for gastric cancer induces G2/M arrest and has an anti-tumor effect on peritoneal carcinomatosis. (2015)
  • Author(s): Natatsuka R, Takahashi T, Serada S, Fujimoto M, Ookawara T, Nishida T, Hara H, Nishigaki T, Harada E, Murakami T, Miyazaki Y, Makino T, Kurokawa Y, Yamasaki M, Miyata H, Nakajima K, Takiguchi S, Kishimoto T, Mori M, Doki Y, Naka T.
  • Journal Title: Br J Cancer Volume: 113(3) Issue: 3 Pages: 433-442
  • DOI: 10.1038/bjc.2015.229
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Annexin A4 induces platinum resistance in a chloride-and calcium-dependent manner. (2014)
  • Author(s): Morimoto A, Serada S, Enomoto T, Kim A, Matsuzaki S, Takahashi T, Ueda Y, Yoshino K, Fujita M, Fujimoto M, Kimura T, Naka T.
  • Journal Title: Oncotarget Volume: 5 Pages: 7776-87
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Screening for novel serum biomarker for monitoring disease activity in rheumatoid arthritis using iTRAQ technology-based quantitative proteomic approach. (2014)
  • Author(s): Serada S, Naka T.
  • Journal Title: Methods Mol Biol. Volume: 1142 Pages: 99-110
  • DOI: 10.1007/978-1-4939-0404-4_12
  • ISBN: 9781493904037, 9781493904044
• [Journal Article] D34(+) /CD38(-) acute myelogenous leukemia cells aberrantly express CD82 which regulates adhesion and survival of leukemia stem cells. (2013)
  • Author(s): Nishioka C, Ikezoe T, Furihata M, Yang J, Serada S, Naka T, Nobumoto A, Kataoka S, Tsuda M, Udaka K, Yokoyama A
  • Journal Title: International Journal of Cancer Volume: 132(9) Issue: 9 Pages: 2006-2019
  • DOI: 10.1002/ijc.27904
  • Peer Reviewed
• [Journal Article] Molecular mechanism underlying the antiproliferative effect of suppressor of cytokine signaling-1 in non-small-cell lung cancer cells. (2013)
  • Author(s): Shimada K, Serada S, Fujimoto M, Nomura S, Nakatsuka R, Harada E, Iwahori K, Tachibana I, Takahashi T, Kumanogoh A, Kishimoto T, Naka T.
  • Journal Title: Cancer Sci. Volume: 104 Issue: 11 Pages: 1483-91
  • DOI: 10.1111/cas.12266
  • Peer Reviewed
• [Journal Article] New findings of kinase switching in gastrointestinal stromal tumor under imatinib using phosphoproteomic analysis. (2013)
  • Author(s): Takahashi T, Serada S, Ako M, Fujimoto M, Miyazaki Y, Nakatsuka R, Ikezoe T, Yokoyama A, Taguchi T, Shimada K, Kurokawa Y, Yamasaki M, Miyata H, Nakajima K, Takiguchi S, Mori M, Doki Y, Naka T, Nishida T.
  • Journal Title: Int J Cancer Volume: 133(11) Pages: 2737-2743
  • DOI: 10.1002/ijc.28282
  • Peer Reviewed