Evaluation of neoantigen cancer vaccination for anti-PD-1 resistant head and neck cancer

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K16841
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56050:Otorhinolaryngology-related
• Research Institution: Gifu University
• Principal Investigator: Shibata Hirofumi 岐阜大学, 大学院医学系研究科, 准教授 (20610421)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 頭頸部がん / 腫瘍免疫 / ネオアンチゲン / TCR-T

Outline of Final Research Achievements

We reported that an overlap antigen containing both MHC-I and MHC-II antigens showed strong antitumor effects in a head and neck cancer mouse model sensitive to anti-PD-1 antibodies (Shibata H et al. Oncoimmunology 2021). We summarized the current status of neoantigen vaccines for head and neck cancer (Shibata H et al. Cancer Sci 2021, Shibata H et al. Front in Oncol 2021). Neoantigen therapy was performed on a head and neck cancer mouse model resistant to anti-PD-1 antibodies. Although it showed temporary antitumor effects, escape tumors soon appeared.
Tissues of oropharyngeal HNSCC and head and neck rare cancers were collected and subjected to RNA-seq and exome-seq to predict neoantigens in silico. We are conducting single-cell RNA analysis and TCR analysis of T cells to identify tumor-specific T cells. TCR derived from T cells with an exhausted phenotype with cytotoxic activity or progenitor cell activity is considered to be promising. Using these data, we are developing TCR-T.

Free Research Field

頭頸部がん

Academic Significance and Societal Importance of the Research Achievements

抗PD-1抗体に感受性の頭頸部がんマウスモデルに対し、MHC-IとMHC-II アンチゲンを両方含むoverlap antigen が強い抗腫瘍効果を示すことを示した(Shibata H et al. Oncoimmunology 2021)。また、ネオアンチゲンワクチンの現状をまとめ報告した(Shibata H et al. Cancer Sci 2021、Shibata H et al. Frontiers in Oncology 2021)。一方で、抗PD-1抗体に抵抗性のがんマウスモデルにはネオアンチゲンワクチンは有意な効果を示さなかった。併用療法やTCR-Tの開発を行い研究を続ける。