Development of a novel anti-cancer immunotherapy based on tumor immunogenicity improvement by abnormal self-antigens

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K22801
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0901:Oncology and related fields
• Research Institution: University of Toyama
• Principal Investigator: Susukida Takeshi 富山大学, 学術研究部薬学・和漢系, 助教 (50880689)
• Project Period (FY): 2020-09-11 – 2022-03-31
• Keywords: 腫瘍免疫 / HLA / CD8陽性T細胞

Outline of Final Research Achievements

Abacavir treatment showed significant tumor growth inhibition associated with CD8+ T cell infiltration into tumor in mice inoculated with HLA-B*57:01 expressing tumor cells, but neither in HLA-B*57:03 (negative allele)expressing tumor nor control tumor inoculated mice. Moreover, the tumor infiltrating CD8+ T cell were immune-activated and proliferated, with secreting cytotoxic cytokines. These results suggested that Abacavir/HLA-B*57:01 interaction could improve tumor immunogenicity in poorly immunogenic tumor, leading to anti-tumor effect.

Free Research Field

腫瘍免疫学

Academic Significance and Societal Importance of the Research Achievements

現在のがん免疫療法の課題の1つに、抗原提示能が低い低免疫原性の腫瘍では細胞傷害性T細胞に認識されないため、免疫チェックポイント阻害剤を介しても細胞傷害性T細胞の活性化が誘導されないことが挙げられる。そのため既存のがん免疫療法では限定的な治療効果しか認められておらず、将来的な適応拡大を視野に入れると高効率な細胞傷害性T細胞の活性化法の開発は必要不可欠であった。本研究で実証した『低免疫原性腫瘍の抗原性を向上させる』がん免疫治療戦略によって、この課題への新たな解決策の提示が期待される。