Investigation of acquired resistance of PD-1 inhibitor with recycle of CART system

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K19591
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Research Field: Tumor biology and related fields
• Research Institution: Kyoto University
• Principal Investigator: Hamanishi Junzo 京都大学, 医学研究科, 講師 (80378736)
• Co-Investigator(Kenkyū-buntansha): 安彦 郁 独立行政法人国立病院機構(京都医療センター臨床研究センター), 内分泌代謝高血圧研究部, 研究員 (20508246) ; 村上 隆介 京都大学, 医学研究科, 特定病院助教 (40782363)
• Project Period (FY): 2017-06-30 – 2020-03-31
• Keywords: 卵巣癌 / がん性腹水 / CART

Outline of Final Research Achievements

A large amount of cancer ascitic fluid could be filtrated and be concentrated by CART system in the patients with recurrent ovarian cancer. The optimal extraction of cancer cells and immune cells from the cancer ascites and next, we identified the several genes associated with chemotherapy-resistance. Mouse ovarian cancer cell lines whose expression was suppressed in syngeneic mouse ovarian cancer cell lines for these genes. Cancer ascites model and combined treatment with an inhibitor of these genes significantly reduced cancer ascites and prolonged survival. Similar results were obtained in an immunodeficient PDX model administered with cancer ascites cells collected by CART. The results show the usefulness of monitoring and reuse of the CART method for immune analysis.

Free Research Field

婦人科腫瘍学

Academic Significance and Societal Importance of the Research Achievements

本研究では卵巣癌だけでなく、がん性腹水を生じる他臓器がんにも応用可能であると考えられるため、CART法による、腫瘍局所の多角的な免疫状態のモニタリングや、新たな免疫抑制因子の発現メカニズムの解明、さらには同因子を標的とした新たな治療選択のシーズ開発の基盤として、様々な再利用（リサイクル）が複数のがん種に対して期待でき、限られた医療材料や資源を有効に活用することが示され、今後の腫瘍免疫研究の新たなツールとして期待できる。