Format

Send to

Choose Destination
Nat Med. 2013 Nov;19(11):1542-6. doi: 10.1038/nm.3358. Epub 2013 Oct 13.

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

Author information

1
1] Department of Immunology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan. [2].

Abstract

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.

PMID:
24121927
DOI:
10.1038/nm.3358
[Indexed for MEDLINE]

Publication types, MeSH terms, Substances, Secondary source ID

Publication types

MeSH terms

Substances

Secondary source ID

Supplemental Content

Full text links

Icon for Nature Publishing Group
Loading ...
Support Center