2023 Fiscal Year Annual Research Report
Development of new cancer therapy using IRE combined with checkpoint blockade
| Project/Area Number |
21K07072
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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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| Keywords | Radiofrequency ablation / IRE / Immune response / immunotherapy |
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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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