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development of superselective intra-arterial infusion chemotherapy for oral cancer using anti-PD-L1 antibody drug

Research Project

Project/Area Number 19K19214
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 57060:Surgical dentistry-related
Research InstitutionThe Nippon Dental University

Principal Investigator

Sakuma Kaname  日本歯科大学, 新潟生命歯学部, 講師 (70733319)

Project Period (FY) 2019-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
KeywordsPD-1 / 局所投与 / CD8 / 動注化学療法 / CTL / Granzyme B / PD-L1 / GranzymeB / 抗PD-L1抗体 / 超選択的動注化学療法 / 抗PD-1抗体 / CD8Tリンパ球
Outline of Research at the Start

抗PD-L1抗体を浅側頭動脈から挿入した逆行性超選択的動注カテーテルより腫瘍部へ直接少量投与することで,高い抗腫瘍効果と,全身投与と比較して重篤な免疫関連有害事象(irAE)の軽減を目指す超選択的動脈注療法の開発である.実現により医療費の大幅な軽減が期待できる.抗PD-1抗体の場合,T細胞に作用するため全身投与が必要であり,irAEが高度に発症するという問題がある.そこで,癌細胞に発現するPD-L1に着目した.マウスモデルを用いて,抗PD-L1抗体薬の低用量局所投与と静脈全身投与の抗腫瘍効果およびPD-L1などの遺伝子発現を比較検討し, 発現変化量,irAEに関してT細胞浸潤で評価を行う.

Outline of Final Research Achievements

Background/Aim: In this study, we investigated the antitumor effect of local and systemic administration of a small amount of anti-PD-1 antibody, overall survival (OS), and the immune environment around cancer using mice. The cell line was transplanted to the back of the mouse. And the anti-PD-1 antibody was locally administered in a small dose (30 mg / body) and systemically (300 mg / body). The tumor shrinkage rate and antitumor effect were examined 29 days after the start of administration. The OS was also compared in each of the other groups. Results: The local low-dose group and the systemic group had the same antitumor effect, and both groups showed a significant difference (p <0.05) from the control group, and the OS also showed a significant prolongation. Conclusion: Local low-dose administration of anti-PD-1 antibody showed the same antitumor effect and OS as systemic normal-dose administration, suggesting that local low-dose administration in oral cancer may be useful.

Academic Significance and Societal Importance of the Research Achievements

近年、免疫療法は口腔がん治療の第4の柱として期待されている。 しかし、1 型糖尿病などの重篤な免疫関連有害事象 (irAE) が報告されている。 したがって、抗 PD-1 抗体を少量の動注療法で局所投与し、全身投与と同等の抗腫瘍効果が得られれば、irAE や医療費の削減につながると考えた。結果として、局所少量投与は、全身通常量投与と比較して非劣性であり、OSに関しても同等の結果であった。また、CD8やグランザイムを局所少量投与ではより強く腫瘍組織内に誘導している可能性があり、局所の少量投与は有用性が高い可能性が示唆された。これは、口腔癌における動注化学療法の有用性へ橋渡しになると考える。

Report

(5 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (2 results)

All 2022 2021

All Journal Article (1 results) (of which Peer Reviewed: 1 results) Presentation (1 results)

  • [Journal Article] An In Vivo Study of Local Administration of Low-dose Anti-PD-1 Antibody Using an Oral Cancer Cell Line.2022

    • Author(s)
      Sakuma K, Kii T, Takahashi H, Suzuki S, Yoshikawa K, Ogawa T, Tanaka A.
    • Journal Title

      Ainticancer Research

      Volume: 42 Issue: 9 Pages: 4293-4303

    • DOI

      10.21873/anticanres.15929

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Presentation] マウス口腔扁平上皮癌細胞株を用いた抗PD-1抗体低用量局所投与と全身投与の比較検討2021

    • Author(s)
      佐久間 要
    • Organizer
      第45回日本頭頸部癌学会
    • Related Report
      2021 Research-status Report

URL: 

Published: 2019-04-18   Modified: 2024-01-30  

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