Development of new cancer therapy using IRE combined with checkpoint blockade
| Project/Area Number |
21K07072
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 49070:Immunology-related
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| Research Institution | Tokyo Medical University |
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Principal Investigator |
杉本 勝俊 東京医科大学, 医学部, 准教授 (20385032)
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| Co-Investigator(Kenkyū-buntansha) |
垣見 和宏 東京大学, 医学部附属病院, 特任教授 (80273358)
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2023: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2022: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2021: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | Radiofrequency ablation / IRE / Immune response / immunotherapy / 腫瘍免疫 / 穿刺局所療法 / アブスコパル効果 / 不可逆電気穿孔法 / ラジオ波焼灼療法 / 局所療法 / 免疫チェックポイント阻害薬 |
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| Outline of Research at the Start |
近年免疫チェックポイント阻害薬が開発され、様々な癌腫において実臨床で使用されている。肝細胞癌においても臨床応用されているが、第3相試験の成績では奏功率は2割程度と高くない状況である。そこで近年では、免疫チェックポイント阻害薬と既存の治療薬との併用療法が期待されている。今回我々は担癌動物モデルを用い、免疫チェックポイント阻害薬と作用機序の異なる各種穿刺局所療法［RFA、不可逆電気穿孔法 (Irreversible electroporation: IRE)、マイクロ波凝固療法（MWA）］との併用療法としての有用性の評価とそのメカニズムを解析し、将来的な臨床応用へ向けた研究基盤を構築する。
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| Outline of Annual Research Achievements |
To evaluate the systemic effects of two different ablation methods: radiofrequency ablation (RFA) and irreversible electroporation (IRE) in animal tumor models. Initially, two sets of groups (treatment and control) were established, both inoculated with Hep55 cells on the right flank on day 0. The treatment group received ablation therapy (either RFA or IRE) on day 7 and subsequently, both groups were reinjected with cells on the left flank (rechallenge) on day 35. The groups were further divided based on the administration of an anti-CD8 antibody or not. In another experiment, mice received same cells on both flanks, with different groups receiving no treatments, PD-1, ablation therapy, or a combination of PD-1 and ablation. The primary lesion was treated with ablation on Day 7. The size of both tumors was measured until day 77. Serum cytokine levels were also monitored at four different timepoints. Both RFA and IRE effectively suppressed primary and secondary tumor growth. CD8+ T cell depletion caused secondary tumors growth in both groups. RFA significantly inhibited distant secondary tumor growth, enhanced by PD-1. Conversely, IRE stimulated distant secondary tumor growth, which was suppressed by PD-1. The most notable cytokine difference was higher IL-6 levels in the IRE group compared to the RFA group. The study reveals that both RFA and IRE induce comparable systemic antitumor immunity with lasting effects. However, IRE uniquely stimulated distant subcutaneous tumor growth, potentially linked to elevated serum IL-6 levels compared to RFA.
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Report
(3 results)
Research Products
(8 results)
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[Journal Article] Comparisons of Radiofrequency Ablation, Microwave Ablation, and Irreversible Electroporation by Using Propensity Score Analysis for Early Stage Hepatocellular Carcinoma.2023
Author(s)
Wada T, Sugimoto K, Sakamaki K, Takahashi H, Kakegawa T, Tomita Y, Abe M, Yoshimasu Y, Takeuchi H, Itoi T.
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Journal Title
Cancers
Volume: 15
Issue: 3
Pages: 732-732
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Significance of Radiofrequency Ablation for Unresectable Colorectal Cancer With Liver Metastases.2021
Author(s)
Tago T, Katsumata K, Udou R, Kasahara K, Mazaki J, Kuwabara H, Enomoto M, Ishizaki T, Nagakawa Y, Sugimoto K, Itoi T, Tsuchida A.
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Journal Title
Anticancer Res.
Volume: 41
Issue: 11
Pages: 5539-5547
DOI
Related Report
Peer Reviewed
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