Identification and characterization of a T-helper peptide from carcinoembryonic antigen

Clin Cancer Res. 2004 Apr 15;10(8):2860-7. doi: 10.1158/1078-0432.ccr-03-0476.

Abstract

Purpose: The purpose of this research was to identify promiscuous T-helper cell determinants (THd) from carcinoembryonic antigen (CEA) to be used to prime T-cell help for cancer therapy. CEA was selected because this antigen is expressed in an important variety of carcinomas.

Experimental design: Potential promiscuous THd from CEA were predicted using available computer algorithms. Predicted peptides were synthesized and tested in binding experiments to different HLA-DR molecules. Binder peptides were then used to prime T-cell responses both in vitro and in vivo.

Results: Twenty 15-mer peptides from CEA were predicted to bind to different HLA-DR molecules. The promiscuous character of these peptides was demonstrated in binding experiments. Fifteen of 20 peptides tested were able to bind to HLA-DR4, but only CEA (625-639) was shown to be presented after processing of recombinant CEA. CEA (625-639) was also found to be presented by HLA-DR53. Moreover, immunization of HLA-DR4 transgenic mice with CEA (625-639) in conjunction with class I epitope OVA (257-264), induced a CTL response specific of OVA (257-264).

Conclusions: CEA (625-639) might be a relevant promiscuous THd peptide for cancer therapy.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Algorithms
  • Animals
  • Antigens / chemistry
  • Carcinoembryonic Antigen / chemistry*
  • Carcinoembryonic Antigen / immunology*
  • Carcinoma / metabolism
  • Cell Line
  • Dose-Response Relationship, Drug
  • Epitopes / chemistry
  • Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
  • HLA-DR Antigens / chemistry
  • HLA-DRB4 Chains
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Peptides / chemistry*
  • Protein Binding
  • Recombinant Proteins / chemistry
  • T-Lymphocytes / metabolism
  • T-Lymphocytes, Cytotoxic / metabolism
  • T-Lymphocytes, Helper-Inducer / chemistry*

Substances

  • Antigens
  • Carcinoembryonic Antigen
  • Epitopes
  • HLA-DR Antigens
  • HLA-DR53
  • HLA-DRB4 Chains
  • Peptides
  • Recombinant Proteins
  • Granulocyte-Macrophage Colony-Stimulating Factor