Development of antigen identification system of tumor-infiltrating lymphocytes

2023 Fiscal Year Final Research Report

• Project/Area Number: 21H02782
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: University of Toyama
• Principal Investigator: Kobayashi Eiji 富山大学, 学術研究部医学系, 助教 (70459733)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: T細胞 / 腫瘍

Outline of Final Research Achievements

We first examined reaction conditions. As a result, it was found that IL-2 production was more sensitive than several cell surface markers to detect antigen-specific reactions. Therefore, we performed antigen identification of TCRs with unknown antigens using the previously studied conditions and cDNA libraries. However, we were unable to detect significant reactions. The reason for this was considered to be the possibility that size of the cDNA library was not sufficient. Therefore, we reexamined the cDNA library preparation and succeeded in producing a cDNA library with a library size 10 times larger than before. Currently, we are using the cDNA library to identify unknown TCR antigens.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

近年、次世代シーケンスにより腫瘍浸潤リンパ球（TIL）のTCRレパトアなど技術の発展により腫瘍抗原特異的TILに関する知見が急速に進んでいる。そのような状況下、抗原未知の腫瘍特異的TILの抗原を目的に抗原同定法の開発が世界中で進められている。本研究では、我々独自の新知見「T細胞Cis-activation」を応用した革新的なTCR抗原同定法の開発を行った。本研究提案によりTILのTCRの抗原同定が短期間に可能になり、TCR遺伝子治療に寄与する高機能TCRの効果や副作用の予測が容易になると考えられる。また、TILの抗原同定により抗原ペプチドを用いたがんペプチドワクチン療法への応用も期待される。