Combination therapy of anti-PD-1 monoclonal antibody with REIC gene therapy for pancreatic cancer

2023 Fiscal Year Final Research Report

• Project/Area Number: 19K17462
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Okayama University
• Principal Investigator: Uchida Daisuke 岡山大学, 大学病院, 講師 (50749215)
• Project Period (FY): 2019-04-01 – 2024-03-31
• Keywords: 遺伝子治療 / REIC遺伝子 / 難治性消化器癌

Outline of Final Research Achievements

We investigated the combined effect of Ad-SGE-REIC and ICI in pancreatic cancer cell lines, biliary tract cancer cell lines, and colorectal cancer cell lines. In vitro, while the efficacy of anti-PD-1 antibody was not fully validated, a certain trend of enhanced efficacy was observed. In vivo validation involved creating a transplant model of Colon-26, a syngeneic colorectal cancer cell line, and assessing tumor immune induction including the abscopal effect with combined Ad-SGE-REIC and ICI. While a local effect of Ad-SGE-REIC was observed, the strong tumor suppressive effect of PD-1 antibody monotherapy overshadowed the potential synergistic effect of combination therapy, thus failing to demonstrate sufficient synergistic effects.

Free Research Field

消化器病学

Academic Significance and Societal Importance of the Research Achievements

免疫チェックポイント阻害薬や分子標的薬をはじめとした様々ながん化学療法が進歩しているが、難治性消化器癌の根治性はまだ十分とはいえない。本研究において検証した遺伝子治療は、がん治療の新たな治療選択肢の一つとして注目されており、岡山大学において発見されたREIC/Dkk-3は治療ターゲットとして有望ながん関連遺伝子として研究開発が進められてきた。本研究では胆膵がんを中心とした難治性消化器癌における遺伝子治療の可能性を示す有用なデータが蓄積された。