Therapy for melanoma with the combination of bleomycin and immune checkpoint inhibitors

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K08760
• 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: St. Marianna University School of Medicine
• Principal Investigator: Kadono Takafumi 聖マリアンナ医科大学, 医学部, 教授 (80292910)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 悪性黒色腫 / PD-1 / CTLA-4 / ブレオマイシン

Outline of Final Research Achievements

Malignant melanoma, a skin cancer derived from moles, generally has a poor prognosis with frequent metastasis. In this study, we used mouse model of melanoma and treat the tumor with bleomycin, an anti-cancer agent that exerts strong DNA damage, in addition to anti-PD-1 antibody, an immune checkpoint inhibitor that enhances tumor immunity. We found that the combination therapy retarded the tumor growth and the possible mechanism includes strong inflammatory cell infiltration and augmentation of inflammatory cytokines. We also found that regional lymph nodes were enlarged with the increase of T cells that have the capacity to migrate into the tumor.

Free Research Field

皮膚悪性腫瘍

Academic Significance and Societal Importance of the Research Achievements

悪性黒色腫は容易に転移し予後が悪い皮膚がんである。近年、がん免疫を高める免疫チェックポイント阻害薬や特定の遺伝子異常を標的とする分子標的薬が登場し、従来よりも生存率が向上したが、未だ十分とは言えない。本研究では、マウスの実験ではあるが、免疫チェックポイント阻害薬による治療にDNA障害性の強い抗がん剤であるブレオマイシンを併用することで、免疫チェックポイント阻害薬単独治療の場合よりも悪性黒色腫の成長速度が低下することが分かり、人への応用が期待できる。