Neoantigen analysis in tumor tissues for development of personalized precision cancer immunotherapy

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K08577
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55010:General surgery and pediatric surgery-related
• Research Institution: Kyushu University
• Principal Investigator: KUBO Makoto 九州大学, 医学研究院, 准教授 (60403961)
• Co-Investigator(Kenkyū-buntansha): 甲斐 昌也 九州大学, 大学病院, 助教 (10755242) ; 大内田 研宙 九州大学, 大学病院, 講師 (20452708) ; 中村 雅史 九州大学, 医学研究院, 教授 (30372741) ; 大西 秀哉 九州大学, 医学研究院, 准教授 (30553276) ; 水元 一博 九州大学, 大学病院, 准教授 (90253418) ; 森崎 隆 九州大学, 医学研究院, 共同研究員 (90291517)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: ネオアンチゲン / がん微小環境 / 腫瘍免疫 / 乳癌 / 腫瘍遺伝子変異量 / 腫瘍浸潤リンパ球 / がんゲノム

Outline of Final Research Achievements

Analysis of total exon DNA + RNA by next-generation sequencer (NGS) using biopsy material from 32 cases of fresh breast cancer showed that the number of gene mutations tended to be higher in triple-negative breast cancer. The number of gene mutations showed a positive correlation with TIL and PD-L1 expression rate (according to immunostaining IHC), T cell activation marker GZMB, and expected number of neoantigen candidates.
Subsequently, the IFN-γ production of autologous lymphocytes against pulsed dendritic cells with the mutant peptide obtained by neoantigen predictive analysis was amplified in a peptide concentration-dependent manner. In addition, the cytotoxicity of lymphocytes stimulated with neoantigen-pulsed dendritic cells to autologous tumors was enhanced. These results suggest that neoantigen is an immune target in the breast cancer microenvironment.

Free Research Field

医歯薬学

Academic Significance and Societal Importance of the Research Achievements

NGSを用いた全エクソンDNA+RNAの解析の結果、乳癌におけるネオアンチゲンの存在を確認し、ネオアンチゲンで刺激されたTリンパ球よって腫瘍に対する細胞障害性は増強されることが示された。副作用の少ない精密個別化医療として細胞医薬への道を開いた社会的意義は大きい。