Development of Immunotherapy for Triple-Negative Breast Cancer Using Local Epigenetic Therapy

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K15529
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Shinshu University
• Principal Investigator: Oba Takaaki 信州大学, 学術研究院医学系(医学部附属病院), 助教 (90724906)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: エリブリン / 免疫細胞 / エピジェネティック治療薬

Outline of Final Research Achievements

In an effort to develop a treatment for triple-negative breast cancer through intratumoral administration of epigenetic therapy agents, we faced the challenge of these agents not being covered by insurance. Thus, our initial goal was to identify chemotherapeutic agents that, when used in combination with epigenetic therapies, would enhance their efficacy. We focused on analyzing the effects of the microtubule inhibitors eribulin and paclitaxel on immune cells. When eribulin was added during the activation process of peripheral blood mononuclear cells (PBMCs) from healthy donors, it notably promoted the proliferation of CD8+ T cells. In contrast, paclitaxel did not exhibit this effect. RNA sequencing analysis revealed that eribulin upregulated gene pathways associated with cell proliferation and immune response, whereas paclitaxel did not induce such changes.

Free Research Field

乳癌

Academic Significance and Societal Importance of the Research Achievements

本研究により、乳がんに対するキードラッグとして使用されるエリブリンがCD8T細胞の増殖を促進させることが明らかとなった。これにより、エピジェネティック治療薬による腫瘍内注入療法のみならず、実臨床ですでに使用されている免疫チェックポイント阻害剤との併用で、さらにこれらの効果を高めることができる可能性が示唆された。今後、エリブリンと他剤との併用療法による、乳癌の新たな治療戦略の開発が期待される。