Development of a radioimmunotherapy (RIT) agent for triple-negative breast cancer

• Project/Area Number: 16K10269
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Radiation science
• Research Institution: Gunma University
• Principal Investigator: Katsumata Natsumi 群馬大学, 医学部附属病院, 医員 (50588811)
• Co-Investigator(Kenkyū-buntansha): 花岡 宏史 群馬大学, 大学院医学系研究科, 特任准教授 (50361390)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: RI内用療法 / トリプルネガティブ乳癌 / 抗VEGF抗体 / 血液クリアランス / アビジン / 放射性医薬品・造影剤

Outline of Final Research Achievements

The overexpression of vascular endothelial growth factor (VEGF) in varying types of solid tumor renders radioimmunotherapy (RIT) with the anti-VEGF antibody bevacizumab (BV) a promising treatment. To enhance RIT efficacy by increasing the radioactivity dose, we evaluated the ability of avidin to accelerate the blood clearance of yttrium-90 (90Y)-labeled biotinylated BV (90Y-Bt-BV) in a xenograft mouse model of triple-negative breast cancer (TNBC). The blood clearance enhancement effect of the avidin chase was demonstrated in the normal mouse studies. The avidin chase enabled an increase in the maximum tolerated dosein tumor-bearing mice and thereby improved the therapeutic effect. These results underscored the potential usefulness of 90Y-bevacizumab-RIT with the avidin chase for the treatment of VEGF-positive TNBC.

Academic Significance and Societal Importance of the Research Achievements

本研究成果は、有効な薬のないトリプルネガティブ乳癌に対する新たな治療薬開発の足掛かりとなるものである。担がんマウスを用いた検討において、十分な治療効果が得られたことから、臨床研究や臨床応用が期待される。また、本研究で用いたアビジン-ビオチンシステムを用いた血液クリアランスを促進する手法は、他の薬剤に対しても応用可能であると考えられ、学術的な意義も大きいものである。

Research Products

• [Journal Article] Bevacizumab Radioimmunotherapy (RIT) with Accelerated Blood Clearance Using the Avidin Chase (2018)
  • Author(s): Yudistiro Ryan、Hanaoka Hirofumi、Katsumata Natsumi、Yamaguchi Aiko、Tsushima Yoshito
  • Journal Title: Molecular Pharmaceutics Volume: 15 Issue: 6 Pages: 2165-2173
  • DOI: 10.1021/acs.molpharmaceut.8b00027
  • Peer Reviewed
• [Presentation] Radioimmunotherapy of triple negative breast cancer using 90Y-DTPA-bevacizumab (2017)
  • Author(s): Hirofumi Hanaoka, Ryan Yudistiro, Aiko Yamaguchi, Tetsuya Higuchi, Yoshito Tsushima
  • Organizer: 第22回放射性薬剤国際シンポジウム（ISRS 2017）