Detection of neoantigens by gene-engineered T cells

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K14403
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Tumor therapeutics
• Research Institution: The University of Tokyo
• Principal Investigator: Kakimi Kazuhiro 東京大学, 医学部附属病院, 特任教授 (80273358)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: 腫瘍免疫 / ネオアンチゲン / TCR / レパトア解析 / 次世代シーケンサー

Outline of Final Research Achievements

Somatic mutations accumulate in cancer cells during cancer progression. Recent studies reported that T cells recognize antigens derived from tumor-specific mutated genes, so-called neoantigens, and mediate immune responses against tumor cells. These neoantigens are not expressed in the thymus and escape from the mechanism of central tolerance; thereby, their immunogenicity is higher than conventional tumor antigens. In this study, we developed the pipeline to predict and prioritize neoantigens by integrating RNA-Seq data with whole-exome sequencing. In addition, we demonstrated that T cell receptor gene sequencing technique using next-generation sequencer is quite useful to detect the expansion of antigen-reactive T cells. It is 1000-times more sensitive to detect antigen-reactive T cells than flowcytometry. Integrating these two novel techniques allow us to identify neoantigens and neoantigen-reactive T cells.

Free Research Field

腫瘍免疫