A study on preparation of single receptor specific lectin and its usefulness

• Project/Area Number: 16K08320
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Drug development chemistry
• Research Institution: Kagawa University
• Principal Investigator: Niki Toshiro 香川大学, 医学部, 助教 (40558508)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: ガレクチン９ / 大腸ガン / 一本鎖抗体 / 融合タンパク質 / KRAS変異 / オートファジー / 免疫学 / 遺伝子

Outline of Final Research Achievements

A fusion protein of Galectin 9 and an anti-EGFR single chain antibody was produced with the goal of generating a modified galectin 9 specifically delivered to colon cancer. The target fusion protein performed two functions as expected, but the productivity was very low even with various trials to improve it. Therefore, the possibility of developing this fusion protein as a drug candidate is not high. However the productivity was improved when a peptide targeting cancer was fused instead of a single chain antibody. I would like to pursue this possibility in the future.

Academic Significance and Societal Importance of the Research Achievements

ガレクチン９は自己免疫疾患やガン等の様々な難治疾患動物モデルで有効性を示すが、複数の受容体・細胞に作用するために薬剤としての開発は難しい。今回の研究は大腸ガン特異的に作用するガレクチン９改変体を作製することで薬剤としての開発ハードルを下げ、新規な抗ガン薬を生み出すことを究極の目標としている。成功すればこれまでのガレクチン９研究成果を最大に社会還元できる。

Research Products

• [Int'l Joint Research] CNRS/Cellvax/Institut Pasteur(フランス)
• [Int'l Joint Research] Keck School of Medicine(米国)
• [Int'l Joint Research] The Wistar Institute/University of Hawaii(米国)
• [Int'l Joint Research] University Medical Center Groningen(オランダ)
• [Int'l Joint Research] University of Groningen(Netherlands)
• [Journal Article] Galectin-9 Mediates HIV Transcription by Inducing TCR-Dependent ERK Signaling (2019)
  • Author(s): Colomb F, Giron LB, Premeaux TA, Mitchell BI, Niki T, Papasavvas E, Montaner LJ, Ndhlovu LC, Abdel-Mohsen M
  • Journal Title: Front Immunol Volume: 10 Pages: 267-278
  • DOI: 10.3389/fimmu.2019.00267
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Lgals9 deficiency attenuates nephritis and arthritis in pristane-induced lupus model of BALB/c mice (2018)
  • Author(s): Zeggar S, Watanabe KS, Teshigawara S, Hiramatsu S, Katsuyama T, Katsuyama E, Watanabe H, Matsumoto Y, Kawabata T, Sada KE, Niki T, Hirashima M, Wada J.
  • Journal Title: Arthritis Rheumatol. Volume: - Issue: 7 Pages: 1089-1101
  • DOI: 10.1002/art.40467
  • Peer Reviewed / Open Access
• [Journal Article] Characterization of neutralizing antibodies reacting with the 213-224 amino-acid segment of human galectin-9 (2018)
  • Author(s): Lhuillier C, Barjon C, Baloche V, Niki T, Gelin A, Mustapha R, Claer L, Hoos S, Chiba Y, Ueno M, Hirashima M, Wei M, Morales O, Raynal B, Delhem N, Dellis O, Busson P
  • Journal Title: PLoS One Volume: 13 Issue: 9 Pages: 1-23
  • DOI: 10.1371/journal.pone.0202512
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Plasma Galectin-9 Concentrations in Normal and Diseased Conditions (2018)
  • Author(s): Niki T, Fujita K,Rosen H, Hirashima M, Masaki T, Hattori T, Hoshino K.
  • Journal Title: Cell Physiol Biochem Volume: 50 Issue: 5 Pages: 1856-1868
  • DOI: 10.1159/000494866
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Galectin-9 Changes Its Function to Maintain Homeostasis (2018)
  • Author(s): Hirashima Mitsuomi、Niki Toshiro、Masaki Tsutomu
  • Journal Title: Trends in Glycoscience and Glycotechnology Volume: 30 Issue: 172 Pages: SJ55-SJ64
  • DOI: 10.4052/tigg.1741.1SJ
  • NAID: 130006319061
  • ISSN: 0915-7352, 1883-2113
  • Peer Reviewed / Open Access
• [Journal Article] Galectin-9 as a Predictive Marker for the Onset of Immune-Related Adverse Effects Associated with Anti-CCR4 MoAb Therapy in Patients with Adult T Cell Leukemia (2017)
  • Author(s): Mohamed TC, Chagana-Yasutan H, Ashino Y, Nakayama W, Suzushima H, Hattori T
  • Journal Title: The Tohoku Journal of Experimental Medicine Volume: 241 Issue: 3 Pages: 201-208
  • DOI: 10.1620/tjem.241.201
  • NAID: 130005461075
  • ISSN: 0040-8727, 1349-3329
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Plasma levels of Galectin-9 reflect disease severity in malaria infection. (2016)
  • Author(s): Dembele BP, Chagan-Yasutan H, Niki T, Ashino Y, Tangpukdee N, Shinichi E, Krudsood S, Kano S, Hattori T.
  • Journal Title: Malar J. Volume: 15 Issue: 1 Pages: 403-403
  • DOI: 10.1186/s12936-016-1471-7
  • Peer Reviewed / Open Access
• [Journal Article] Human Galectin-9 Is a Potent Mediator of HIV Transcription and Reactivation. (2016)
  • Author(s): Abdel-Mohsen M, Chavez L, Tandon R, Chew GM, Deng X, Danesh A, Keating S, Lanteri M, Samuels ML, Hoh R, Sacha JB, Norris PJ, Niki T, Shikuma CM, Hirashima M, Deeks SG, Ndhlovu LC, Pillai SK.
  • Journal Title: PLoS Pathog. Volume: 12(6） Issue: 6 Pages: e1005677-e1005677
  • DOI: 10.1371/journal.ppat.1005677
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Acute Liver Failure Study Group. Association Between Plasma Level of Galectin-9 and Survival of Patients With Drug-Induced Acute Liver Failure. (2016)
  • Author(s): Rosen HR, Biggins SW, Niki T, Gralla J, Hillman H, Hirashima M, Schilsky M, Lee WM
  • Journal Title: Clin Gastroenterol Hepatol Volume: 14 Issue: 4 Pages: 606-612
  • DOI: 10.1016/j.cgh.2015.09.040
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Patent(Industrial Property Rights)] GALECTIN MOLECULES AS IMMUNOTHERAPY TARGETS. (2018)
  • Inventor(s): Ndhlovu L and Niki T.
  • Industrial Property Rights Holder: Ndhlovu L and Niki T.
  • Industrial Property Rights Type: 特許
  • Filing Date: 2018
  • Overseas