Immunophoto therapy targeting cancer stem cell in colorectal cancer

• Project/Area Number: 17K09385
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: The University of Tokushima
• Principal Investigator: MUGURUMA Naoki 徳島大学, 大学院医歯薬学研究部(医学域), 准教授 (90325283)
• Co-Investigator(Kenkyū-buntansha): 高山 哲治 徳島大学, 大学院医歯薬学研究部(医学域), 教授 (10284994) ; 岡本 耕一 徳島大学, 病院, 講師 (60531374)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: がん幹細胞 / 大腸癌 / 分子イメージング / オルガノイド / 光線免疫療法 / 光免疫治療 / 光免疫療法

Outline of Final Research Achievements

Organoids were successfully developed and cultured from 20 cases of colorectal cancer and flowcytometry was performed to evaluate expresssion of cancer stem cell markers such as LGR5, CD133 and CD44v6. Chemoresistance was noted in organoids showing high expression of LGR5 and low expression of CD133. Organoids were implanted to nude mice and tumor resembling original human tumor was created. Gastrointestinal stromal tumor expressing c-kit was implanted to nude mice and treated with infrared laser irradiation in combination with intravenous injection of IR700-labeled anti-c-kit antibody. Tumor regression rate was 90% and tumor waa completely eradicated in 4 out of 7 mice. In these results, it is expected to realize photoimmunotherapy targeting cancer stem cell in colorectal cancer.

Academic Significance and Societal Importance of the Research Achievements

本研究では、大腸癌幹細胞としてLgr5陽性細胞に着目し、Lgr5陽性細胞中でCD133陽性率が高いものは抗がん剤薬剤感受性が高く、CD133陽性率が低いものが薬剤耐性に関わっている可能性を示し、これまでにない新たな知見を得た。さらにオルガノイドをヌードマウスへの移植を試み、細胞株とは異なりヒト組織を反映した腫瘍形成を確認した。代用したGIST細胞でレーザー焼灼を行ったところ、標識抗体投与群のみで高い治療効果が得られたことから、Lgr5などの表面マーカーを標的とする大腸癌幹細胞の光免疫治療への応用が期待された。光免疫治療法の確立により化学療法抵抗性を示す大腸癌の予後改善が期待される。