Radioimmunotherapy with Anti-podoplanin cancer-specific monoclonal antibody

• Project/Area Number: 18K07778
• 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: National Institutes for Quantum and Radiological Science and Technology
• Principal Investigator: Sudo Hitomi 国立研究開発法人量子科学技術研究開発機構, 放射線医学総合研究所 分子イメージング診断治療研究部, 主任研究員(任常) (10415416)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: ポドプラニン / 放射免疫療法

Outline of Final Research Achievements

Radioimmunotherapy (RIT) is a selective internal radiation therapy using radiolabeled monoclonal antibodies against tumor-associated antigens. In this study, we radiolabeled antibodies which recognized cancer specific podoplanin and evaluated the potential of podoplanin-targeted RIT using mouse model. Giving 90Y- and 225Ac-labeled anti-podoplanin antibodies showed markedly antitumor effect without obvious adverse effects. These results suggests that the radiolabeled anti-podoplanin antibody is a promising RIT agent as a new therapeutic option for podoplanin-expressing tumors.

Academic Significance and Societal Importance of the Research Achievements

マウス皮下腫瘍と比較して、患者由来組織でのポドプラニンの発現は高い傾向にあったことから、この抗体を用いたRITは中皮腫患者ではより高い治療効果が期待できる。RI標識した本抗体が臨床応用されれば、中皮腫の新たな画期的な治療法となるだろう。また、ポドプラニンは脳腫瘍など様々ながんで高発現していることが報告されており、本抗体を用いたRITが中皮腫以外の固形がんの治療にも応用が可能であり、難治性固形がんの治療法開発に大きな進展をもたらすと期待される。

Research Products

• [Journal Article] Radiolabeled Human Monoclonal Antibody 067-213 has the Potential for Noninvasive Quantification of CD73 Expression (2020)
  • Author(s): Sudo Hitomi、Tsuji Atsushi B.、Sugyo Aya、Kurosawa Gene、Kurosawa Yoshikazu、Alexander David、Tsuda Hiroyuki、Saga Tsuneo、Higashi Tatsuya
  • Journal Title: International Journal of Molecular Sciences Volume: 21 Issue: 7 Pages: 2304-2304
  • DOI: 10.3390/ijms21072304
  • Peer Reviewed / Open Access
• [Journal Article] Therapeutic efficacy evaluation of radioimmunotherapy with 90Y-labeled anti-podoplanin antibody NZ-12 for mesothelioma (2019)
  • Author(s): Sudo Hitomi、Tsuji Atsushi B.、Sugyo Aya、Saga Tsuneo、Kaneko Mika K.、Kato Yukinari、Higashi Tatsuya
  • Journal Title: Cancer Science Volume: 110 Issue: 5 Pages: 1653-1664
  • DOI: 10.1111/cas.13979
  • Peer Reviewed / Open Access
• [Presentation] A novel anti-podoplanin antibody NZ-16 has the potential as a radioimmunotherapy agent for solid tumors (2020)
  • Author(s): Hitomi Sudo, Atsushi B. Tsuji, Aya Sugyo, Kentaro Fujiwara, Mika K. Kaneko, Yukinari Kato, and Tatsuya Higashi
  • Organizer: 第79回日本癌学会学術総会
• [Presentation] Preclinical evaluation of an anti-podoplanin antibody NZ-12 as a radioimmunotherapy agent for malignant mesothelioma (2019)
  • Author(s): Hitomi Sudo, Atsushi B. Tsuji, Aya Sugyo, Tsuneo Saga, Mika K. Kaneko, Yukinari Kato, and Tatsuya Higashi
  • Organizer: 第78回日本癌学会学術総会
• [Presentation] Development of a noninvasive imaging technique to detect the expression of CD73 mediating immunosuppression in cancer (2018)
  • Author(s): Hitomi Sudo, Atsushi B. Tsuji, Aya Sugyo, Mitsuru Koizumi, Gene Kurosawa, Yoshikazu Kurosawa, Tsuneo Saga, Tatsuya Higashi
  • Organizer: 第77回日本癌学会学術総会