Development of a novel cancer immunotherapy targeting the immune checkpoint molecule, HLA-F.

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07246
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Nara Medical University
• Principal Investigator: Ouji-Sageshima Noriko (下嶋典子) 奈良県立医科大学, 医学部, 助教 (30398432)
• Co-Investigator(Kenkyū-buntansha): 伊藤 利洋 奈良県立医科大学, 医学部, 教授 (00595712)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: HLA-F / immunotherapy / PDX / SCID / SCID-beige / tumor

Outline of Final Research Achievements

We performed this research with the aim of developing a new cancer immunotherapy targeting HLA-F, one of the HLA class I molecules, as an immune checkpoint molecule.
We have already detected that IFN-γ production is enhanced, when tumor cells, tumor-infiltrating lymphocytes, and anti-HLA-F antibodies were co-cultured. To elucidate the mechanism, we established patient-derived colon cancer cells expressing HLA-F and produced a mouse model. As a result, although we succeeded in producing a tumor-bearing model mouse using HLA-F-positive patient-derived colon cancer cells, we were unable to establish a mouse model transfected with human NK cells to verify the HLA-F blocking effect. In the future, we plan to verify the HLA-F blocking effect in an in vitro system.

Free Research Field

腫瘍免疫

Academic Significance and Societal Importance of the Research Achievements

免疫療法は、第3のがん治療法として期待されているが、適用のないがん種もあるため、新たな標的分子の探索は継続して必要である。HLA-Fは幅広い種の腫瘍細胞に発現しており、腫瘍マーカーだけでなく免疫療法の新規標的分子として期待できる。
臨床検体から継代可能な患者由来大腸癌細胞を作製し、マウスモデルを作成したことで、HLA-Fが生体内においても腫瘍細胞膜表面に発現していることが明らかとなった。本研究成果は幅広い種の腫瘍細胞に発現するHLA-Fを利用したがん免疫療法の開発につながると考える。