Cell-mediated immunity induction by anti-HER2 antibody treatment for HER2-positive breast cancer and development of new immunotherapy

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K18051
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55010:General surgery and pediatric surgery-related
• Research Institution: Shiga University of Medical Science
• Principal Investigator: Kitamura Mina 滋賀医科大学, 医学部, 医員 (10587934)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 免疫治療 / 乳癌薬物療法 / 腫瘍浸潤リンパ球 / 抗HER2抗体 / 免疫チェックポイント阻害剤 / 免疫逃避 / 細胞性免疫

Outline of Final Research Achievements

The purpose of the research was to elucidate the mechanism of the antitumor effect by molecular-targeted antibody therapeutic agents targeting tumor cell surface molecules from the aspect of local immunity and to establish a new antibody treatment method. In the mouse HER2-positive breast cancer model, anti-HER2 antibody treatment induced HER2-specific cytotoxic T cells (CTL), and CTL infiltrated into the tumor tissue. Docetaxel also induces TIL, but when used in combination with an anti-HER2 antibody, TIL increased further. Breast cancer resected specimens treated with chemotherapy plus anti-HER2 antibody for neoadjuvant chemotherapy have significantly more CD4 and CD8-positive cell infiltration than breast cancer tissue treated with chemotherapy alone. Thus, anti-HER2 antibody therapy may induce cellular immunity to HER2-positive breast cancer.

Free Research Field

乳腺外科

Academic Significance and Societal Importance of the Research Achievements

HER2陽性固形癌で抗HER2抗体が治療に利用されているが、本研究により抗HER2抗体が乳癌局所にHER2特異的CTLの集積が増強され細胞性免疫が誘導されることが示唆された。このことは、免疫チェックポイント阻害剤などの併用がHER2陽性癌に対するさらなる抗腫瘍効果増強をもたらす可能性があることを示しており、今後の治療法開発への有用な情報となるであろう。