Development of the combination therapy with ultrasound stimulated microbubbles and anti PD-1 antibody to overcome resistance to cancer immunotherapy

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K22505
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0403:Biomedical engineering and related fields
• Research Institution: Teikyo University
• Principal Investigator: Munakata Lisa 帝京大学, 薬学部, 助教 (90879694)
• Project Period (FY): 2020-09-11 – 2022-03-31
• Keywords: がん免疫 / マイクロバブル / 超音波 / 免疫チェックポイント阻害剤

Outline of Final Research Achievements

Cancer immunotherapy is one of the most ideal therapies to prolong the lifetime of cancer patients. However, its overall response rate is not so high. To overcome this problem, we focused on the mechanical energy derived from ultrasound stimulated microbubbles and developed the combination therapy of this and immune checkpoint inhibitor (anti PD-1 antibody). To assess the antitumor effect, tumor inoculated mice were treated with ultrasound stimulated microbubbles and anti PD-1 antibody. As a result of this, the rate of tumor regression increased in murine colon carcinoma model. Moreover, it was confirmed the antitumor effect by this combination therapy in murine breast carcinoma model. Further, the number of antitumoral immune cells increased by this combination therapy. From these results, the combination therapy with ultrasound stimulated microbubbles and anti PD-1 antibody is expected as an useful cancer immunotherapy.

Free Research Field

薬学

Academic Significance and Societal Importance of the Research Achievements

本研究では、マイクロバブルと超音波による治療をがん免疫療法治療薬である抗 PD-1 抗体治療に併用し、その抗腫瘍効果を評価した。その結果、大腸がんモデルマウスにおいて、腫瘍の完全退縮例の増加が確認された。また、乳がんモデルマウスにおいて、腫瘍増殖の抑制が確認された。これらの結果は、マイクロバブルと超音波による治療が、異なるがん種に対して抗 PD-1 抗体の治療効果を増強する有用な併用療法になることを示唆している。そのため、本治療法の最適化を進めることで、現在問題となっているがん免疫療法の奏効率を向上するための有用な併用療法になり得ると期待される。