Research on drug seeds creation targeting glycosyltransferase in non-small cell lung cancer

• Project/Area Number: 16K19437
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Respiratory organ internal medicine
• Research Institution: Hokkaido University
• Principal Investigator: Honma Rio 北海道大学, 医学研究院, 助教 (40709276)
• Research Collaborator: Akita Hirotoshi
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 糖転移酵素 / FUT8 / 肺癌

Outline of Final Research Achievements

Research on drug seeds creation targeting FUT8 glycosyltransferase in non-small cell lung cancer (NSCLC) was performed, using CRISPR-Cas9 system to knockdown FUT8 and produce FUT8-knocked-down cell lines, although stable cell lines were not obtained.
14 (43.8%) of 32 NSCLC cell lines screened for the expression of PD-L1 showed PD-L1 expression. PD-L1 expression was not correlated with 3’UTR miRNA seeding region mutations of PD-L1 and copy number of the gene.

Academic Significance and Societal Importance of the Research Achievements

FUT8糖転移酵素を制御することによって、FUT8糖鎖修飾標的PD-L1の機能抑制による腫瘍免疫活性化による新たな創薬シーズ創出することは学術的意義が大きい。特に抗PD-1抗体薬、抗PD-L1抗体薬の効果増強や耐性克服の上で。
32株の肺癌細胞株についてPD-L発現をウエスタンブロット法／免疫細胞染色法で解析したところ、14細胞株（43.8%）においてPD-L1発現を認め、PD-Lが非小細胞肺癌の有力な治療標的であることを示すことができた。