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Validation of cytotoxic T cell activity when immune checkpoint inhibitors are combined with other cancer treatments

Research Project

Project/Area Number 19K16866
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 50020:Tumor diagnostics and therapeutics-related
Research InstitutionHiroshima University

Principal Investigator

Sakamoto Shinjiro  広島大学, 病院(医), 助教 (30816541)

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: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywordsimmunotherapy / Cytotoxic T lymphocyte / anti-PD-1 antibody / anti-CTLA-4 antibody / cancer peptide vaccine / がんワクチン / 免疫チェックポイント阻害剤 / 細胞障害性T細胞 / 癌 / ペプチドワクチン / 癌ワクチン / バイオマーカー
Outline of Research at the Start

In vitroにて、ペプチドワクチン療法と免疫チェックポイント阻害剤の併用により、単独治療よりも癌特異的細胞障害性T細胞自体の誘導増強や、癌特異的細胞障害性T細胞誘導の細胞障害活性の上昇を証明し、今後、in vivoや実臨床における、ペプチドワクチン療法と免疫チェックポイント阻害剤の併用による抗腫瘍効果の増強が得られるかを予測する。

Outline of Final Research Achievements

Sufficient results could not be obtained regarding the verification of useful combination therapy such as combined immunotherapy in cancer treatment.
Lymphocytes stimulated with anti-PD-1 antibody, anti-CTLA-4 antibody, and cancer peptide were co-cultured with tumor cells and evaluated for cytotoxic activity. However, in the verification under combined use, the reaction with cancer peptide was very weak and difficult to evaluate. Moreover, there was no difference in cell surface markers and cytokines related to immune reaction. Stimulation of only lymphocytes, which is different from biological reactions, is thought to be due to weak relationships between immune cells. We also tried co-culturing and stimulating lymphocytes and monocytes, but we were not able to obtain sufficient results.

Academic Significance and Societal Importance of the Research Achievements

がんに対する免疫療法は長期の治療効果が得られる可能性があるが、免疫複合療法での免疫関連有害事象のような副作用問題や治療効果の予測因子が十分解明されていないことが現状の課題である。これらを解明するために、in vivoで多くの有用な報告がされているが、人への適応となると十分な効果が得られない。そのため人の細胞を使用し、in vitroで検証が可能となれば早期にこれらの課題が解明される可能性がある。本研究課題において十分な成果は得られなかったが、本検証内容をさらに発展させることで、生体内に近い反応をin vitroで検証できるようになる可能性があると考える

Report

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

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

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