Production of monoclonal antibodies using B cells derived from patients and their clinical application

• Project/Area Number: 18K07293
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Kanazawa University
• Principal Investigator: Takamatsu Hiroyuki 金沢大学, 医学系, 講師 (70401932)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: HLA / モノクローナル抗体 / 微小残存病変 / 造血器腫瘍 / 多発性骨髄腫 / 再生不良性貧血 / HLA抗原 / リンパ系腫瘍 / 癌精巣抗原 / 血液腫瘍

Outline of Final Research Achievements

In this study, using peripheral B cells derived from donors and cell-arrays we have created novel monoclonal antibodies that could not be made using conventional methods. In addition to monoclonal antibodies against HLA-B61 and Bw4, we could create recombinant cells that secrete antibodies against HLA-A33, B13, B48, B53 and B54 and so on. Using these novel monoclonal antibodies, we can monitor minimal residual disease, chimerism after allogeneic stem cell transplantation and identify patients with aplastic anemia who respond to immunosuppressive treatments by flow cytometry.

Academic Significance and Societal Importance of the Research Achievements

これまでに白血球の血液型であるHLAの一部に対するモノクローナル抗体は通常の実験動物に免疫をする方法では作製することができなかった。本研究では患者B細胞と細胞アレイを使用することによって、新規抗HLAモノクローナル抗体を初めて作製できた。今回作製に成功した新規の抗HLAモノクローナル抗体を用いることで簡便にごく少数の血液がん細胞を検出することができ、再発の早期診断が可能になった。また、免疫抑制療法が効きやすい再生不良性貧血の患者も同定可能になった。

Research Products

• [Journal Article] HLA class I allele-lacking leukocytes predict rare clonal evolution to MDS/AML in patients with acquired aplastic anemia. (2021)
  • Author(s): Hosokawa K, Mizumaki H, Yoroidaka T, Maruyama H, Imi T, Tsuji N, Urushihara R, Tanabe M, Zaimoku Y, Nguyen MAT, Tran DC, Ishiyama K, Yamazaki H, Katagiri T, Takamatsu H, Hosomichi K, Tajima A, Azuma F, Ogawa S, Nakao S.
  • Journal Title: Blood Volume: － Issue: 25 Pages: 3576-3580
  • DOI: 10.1182/blood.2020010586
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A frequent nonsense mutation in exon 1 across certain HLA-A and -B alleles in leukocytes of patients with acquired aplastic anemia. (2020)
  • Author(s): Mizumaki H, Hosomichi K, Hosokawa K, Yoroidaka T, Imi T, Zaimoku Y, Katagiri T, Nguyen MAT, Tran DC, Elbadry MIY, Chonabayashi K, Yoshida Y, Takamatsu H, Ozawa T, Azuma F, Kishi H, Fujii Y, Ogawa S, Tajima A, Nakao S.
  • Journal Title: Haematologica Volume: － Issue: 6 Pages: 247809-247809
  • DOI: 10.3324/haematol.2020.247809
  • Peer Reviewed / Open Access / Int'l Joint Research