Cellular and Molecular analyses of cancer-associated antigen-specific cytotoxic T cells by multidimensional methods and development of novel cancer immunotherapy

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07729
• 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: Osaka University
• Principal Investigator: Nishida Sumiyuki 大阪大学, 医学系研究科, 講師 (00403189)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: がん免疫療法 / がんワクチン / WT1 / T細胞受容体 / 膵臓がん

Outline of Final Research Achievements

WT1 is a promising cancer-associated antigen. We, here, evaluated the qualitative and functional changes in WT1-specific cytotoxic T cells, WT1-CTLs, induced during the combination therapy with cytotoxic drug and WT1 cancer vaccine for advanced pancreatic cancer patients.
It was essential for long-term clinical efficacy that WT1-CTLs, induced after treatment, obtained a memory function to maintain their antitumor immunity. Further, we found that some TCR clones of WT1-CTLs were shared among patients who had exhibited clinical efficacy. We will link these TCRs to the future development of new cancer immunotherapies.

Free Research Field

がん免疫療法

Academic Significance and Societal Importance of the Research Achievements

今回の成果はWT1を標的としたがん免疫療法（細胞療法）の開発につながる。個々の患者のがん特異的なネオ抗原に対するT細胞受容体の同定が個別化医療となることに対して、汎腫瘍抗原であるWT1に特異的なキラーT細胞が持つT細胞受容体を同定することは、膵癌のみならずWT1を発現するがんを患った患者に応用が可能であることを意味する。免疫チェックポイント阻害薬の効果が乏しいとされる、いわゆる“cold”ながんに対する治療戦略を将来発展させうる１つの成果である。