Therapy against HCC by potential ability of CpG endowed by DDS

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07175
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Osaka University
• Principal Investigator: Tsujimura Naoto 大阪大学, 大学院医学系研究科, 招へい教員 (10804198)
• Co-Investigator(Kenkyū-buntansha): 柴田 理志 大阪大学, 大学院医学系研究科, 特任講師(常勤) (00423153) ; 山本 浩文 大阪大学, 大学院医学系研究科, 教授 (30322184) ; 横山 雄起 大阪大学, 大学院医学系研究科, 助教 (60615714)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 肝細胞癌 / CpG / DDS / インターフェロンアルファ

Outline of Final Research Achievements

We had experienced several advanced HCC cases to which 5-FU/IFN alpha therapy gave marked therapeutic efficacy, but the therapy was not approved as a standard therapy at that time. CpG nucleic acids containing non-methylated CG sequences are being used in clinical trials of cancer and infectious diseases, but the efficacy has not been proved thus far. In this study, we have succeeded to induce IFN alpha/gamma at high levels in HCC cells by combination of K type CpG and our unique DDS system. This is particularly important because D type CpG usually induces IFN alpha but clinically available K type CpG does not. This result was also confimed with colorectal cancer cells. Our findings may open a new avenue to novel therapy against HCC and other solid tumors.

Free Research Field

消化器外科

Academic Significance and Societal Importance of the Research Achievements

本研究の結果、CpG核酸を独自のDDSに搭載することで肝細胞癌に対する新規の治療法に繋がる可能性がある。この治療法は核酸医薬に分類され、通常のマウス試験では核酸による治療は、小さな腫瘍にしか適応できないことが多いが、本法によれば4～10倍程度大きなマウス腫瘍にも治療効果がみられた。この結果は、肝細胞癌のみではなく大腸癌のマウス腫瘍モデルでも確認されたことから、強力な抗腫瘍効果を示す核酸を使った治療法となることが期待される。