A new cloning and expression system yields and validates TCRs from blood lymphocytes of patients with cancer within 10 days

Eiji Kobayashi, Eishiro Mizukoshi, Hiroyuki Kishi*, Tatsuhiko Ozawa, Hiroshi Hamana, Terumi Nagai, Hidetoshi Nakagawa, Aishun Jin, Shuichi Kaneko, Atsushi Muraguchi

*この論文の責任著者

研究成果: ジャーナルへの寄稿学術論文査読

78 被引用数 (Scopus)

抄録

Antigen-specific T cell therapy, or T cell receptor (TCR) gene therapy, is a promising immunotherapy for infectious diseases and cancers. However, a suitable rapid and direct screening system for antigen-specific TCRs is not available. Here, we report an efficient cloning and functional evaluation system to determine the antigen specificity of TCR cDNAs derived from single antigen-specific human T cells within 10 d. Using this system, we cloned and analyzed 380 Epstein-Barr virus-specific TCRs from ten healthy donors with latent Epstein-Barr virus infection and assessed the activity of cytotoxic T lymphocytes (CTLs) carrying these TCRs against antigenic peptide-bearing target cells. We also used this system to clone tumor antigen-specific TCRs from peptide-vaccinated patients with cancer. We obtained 210 tumor-associated antigen-specific TCRs and demonstrated the cytotoxic activity of CTLs carrying these TCRs against peptide-bearing cells. This system may provide a fast and powerful approach for TCR gene therapy for infectious diseases and cancers.

本文言語英語
ページ(範囲)1542-1546
ページ数5
ジャーナルNature Medicine
19
11
DOI
出版ステータス出版済み - 2013/11

ASJC Scopus 主題領域

  • 生化学、遺伝学、分子生物学一般

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