Preclinical exploratory research and development of new boron drugs for Boron-neutron immunotherapy against melanoma

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K08652
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53050:Dermatology-related
• Research Institution: Shimane University (2021-2022); Okayama University (2020)
• Principal Investigator: Yamasaki Osamu 島根大学, 学術研究院医学・看護学系, 教授 (90294462)
• Co-Investigator(Kenkyū-buntansha): 道上 宏之 岡山大学, 中性子医療研究センター, 准教授 (20572499)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: BNCT / メラノーマ / 複合免疫療法 / 抗PD-1抗体

Outline of Final Research Achievements

Immunotherapies with immune checkpoint inhibitors are successful treatments for advanced melanoma; however, it remains important to search for improved combination therapies. Boron-neutron capture therapy (BNCT) is a cell-level local particle beam therapy in which a boron agent taken up by tumor cells is irradiated with neutrons. Tumor-targeted boron drugs are amino acid derivatives that are highly compatible with melanoma and have been successfully turned into a treatment with neutron generators. We confirmed the effectiveness of the world's first combined immunotherapy that incorporates immune checkpoint inhibitors with BNCT. Using an advanced melanoma mouse model, we report strong immunotherapeutic effects by cell-mediated immunity at the irradiation site and distant sites, in addition to the direct antitumor effects of BNCT, without damage to normal tissues.

Free Research Field

皮膚悪性腫瘍

Academic Significance and Societal Importance of the Research Achievements

メラノーマ動物モデルを用いた実験でBNCTによる免疫療法増強効果とアブスコパル効果が確認できた。BNCTが免疫チェックポイント阻害薬が奏効しない進行期メラノーマ患者の治療選択肢として期待でき、共同研究を進めている進行期メラノーマに対するBNCTの複合免疫療法の臨床研究に発展できる。メラノーマに対して研究レベルで局所療法としてBNCTが施行されているが、免疫複合療法という観点から進行期メラノーマ症例に対する新規治療法をめざすことは画期的である。さらに免疫療法との相乗効果を期待できる複合免疫療法構想は、BNCTの適応が予想される頭頸部癌や乳癌、消化器癌などへも発展が期待される。