Adoptive CTL therapy using neo-antigen-specific TCR-gene induced T cells

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08751
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Shiga University of Medical Science
• Principal Investigator: Murata Satoshi 滋賀医科大学, 医学部, 講師 (90239525)
• Co-Investigator(Kenkyū-buntansha): 住本 秀敏 滋賀医科大学, 医学部, 特任講師 (00306838) ; 下地 みゆき 滋賀医科大学, 医学部, 技術補佐員 (50796448) ; 谷 眞至 滋賀医科大学, 医学部, 教授 (60236677)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 免疫細胞治療 / TCR改変T細胞 / 腫瘍浸潤リンパ球 / 腫瘍ネオ抗原 / 免疫チェックポイント阻害剤 / T細胞補助刺激因子

Outline of Final Research Achievements

We successfully created PDX (patient-derived xenograft) models by implanting surgically removed colon cancer, gastric cancer, and breast cancer tumors into immunodeficient mice. We identified somatic mutations in cancer tissues by sequencing DNA from both cancer and normal tissues of each patient. Through this, we found numerous mutant antigen peptides that have a high affinity to the patient's HLA-class I, making them Neo-Ag candidates. We further narrowed down these Neo-Ag peptides based on high lymphocyte reactivity using mass spectrometry. Additionally, we conducted an experiment where we introduced Flu-specific TCRαβ cDNA into human CD8+ T cells and evaluated the phenotype of the TCR-introduced T cells. We believe that combining this platform with PDX models can be an effective approach for the rapid development of adaptive immunotherapy.

Free Research Field

がん免疫学　腫瘍外科学

Academic Significance and Societal Importance of the Research Achievements

患者腫瘍由来の高効率なNeo-Ag同定技術を基に、患者リンパ球由来のNeo-Ag特異的TCR導入CTLを樹立し、OX40刺激下培養によるメモリーCTL誘導技術、さらにICI治療を組み合わせ、独自性の高い高効率な養子免疫細胞療法の開発することにより、既存技術を超える新しいプラットフォームが構築でき、患者ネオ抗原を利用した個別化新規養子免疫細胞療法の臨床開発が可能になる。