A novel treatment of rheumatoid arthritis by photoimmunotherapy with anti-mouse IL-6R antibody

• Project/Area Number: 18K07626
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52040:Radiological sciences-related
• Research Institution: University of Tsukuba (2020-2021); Gunma University (2018-2019)
• Principal Investigator: NAKAJIMA TAKAHITO 筑波大学, 医学医療系, 教授 (70375559)
• Co-Investigator(Kenkyū-buntansha): 米本 由木夫 群馬大学, 大学院医学系研究科, 研究員 (50400734) ; 岡邨 興一 群馬大学, 医学部附属病院, 講師 (90527722)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• 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: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 関節リウマチ / 光免疫療法 / 抗体 / IL-6受容体 / 光イメージング / 関節炎 / ＩＬ－６受容体 / マウスモデル / マクロファージ / 近赤外線

Outline of Final Research Achievements

The technology of photoimmunotherapy, which was developed for cancer treatment, is applied to the murine arthritis model. In photoimmunotherapy, after making a conjugate with a photosensitizer called IR700 and an antibody against an antigen expressed on the surface of cancer cells, near-infrared light is irradiated 24 hours after administration of a conjugate intravenously or intraperitoneally. In this study, photoimmunotherapy was performed targeting the IL-6 receptor, which is used for treatment in clinical practice. A conjugate with a mouse anti-IL-6 receptor antibody and IR700 was created. A mouse model of collagen-induced arthritis was treated by photoimmunotherapy, and the degree of progression of arthritis was clarified by irradiating the joints and spleen with near-infrared light.

Academic Significance and Societal Importance of the Research Achievements

関節リウマチは早期に治療介入することで、二次性の変形性関節症を予防して、患者のQOLの改善を期待できる。一方で、現在用いられている生物学的製剤や抗体療法はまれに重篤な副作用を来すことが分かっており、光免疫療法の技術を応用することで、より少ない抗体量で、より高い効果を期待できる。これまでがん治療に用いられてきた光免疫療法を関節リウマチに応用した新しい着眼点による研究である。

Research Products

• [Journal Article] Imaging modalities for monitoring acute therapeutic effects after near-infrared photoimmunotherapy in vivo (2022)
  • Author(s): Xieyi Zhang, Takahito Nakajima, Kenta Mizoi, Yoshito Tsushima, Takuo Ogihara
  • Journal Title: Journal of Biophotonics Volume: 15 Issue: 1
  • DOI: 10.1002/jbio.202100266
  • Peer Reviewed / Open Access
• [Journal Article] 64Cu-ATSM and 99mTc(CO)3-DCM20 potential in the early detection of rheumatoid arthritis (2021)
  • Author(s): Dam TT, Hanaoka H, Nakajima T, Yamaguchi A, Okamura K, Chikuda H, Tsushima Y.
  • Journal Title: Modern Rheumatology Volume: 31(2) Issue: 2 Pages: 350-356
  • DOI: 10.1080/14397595.2020.1751945
  • Peer Reviewed / Open Access
• [Journal Article] Axillary lymph-node metabolic activity assessment on 18F-FDG-PET/CT in rheumatoid arthritis patients treated with biologic therapies. (2020)
  • Author(s): Dam TT, Okamura K, Nakajima T, Yonemoto Y, Suto T, Arisaka Y, Tomonaga H, Tachibana M, Tajika T, Vu LD, Chikuda H, Tsushima Y.
  • Journal Title: Scandinavian Journal of Rheumatology Volume: 49 Issue: 2 Pages: 96-104
  • DOI: 10.1080/03009742.2019.1650106
  • Peer Reviewed / Open Access
• [Presentation] A Pictorial Review of Positron Emission Tomography with 18F-FDG in Rhematoid Arthritis (2020)
  • Author(s): Trang T. Dam, Takahito Nakajima
  • Organizer: 第105回北米放射線学会
  • Int'l Joint Research
• [Presentation] A Pictorial Review of Positron Emission Tomography with 18F-FDG in Rhematoid Arthritis (2019)
  • Author(s): Trang T. Dam
  • Organizer: 105th Annual meeting of Radiology Society of North America
  • Int'l Joint Research
• [Funded Workshop] 105th Annual Meeting of Radiology Society of North America (2019)