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Clin Cancer Res. 2004 Apr 15;10(8):2860-7.

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

Author information

1
Facultad de Medicina y Clínica Universitaria, Fundación para la Investigación Médica Aplicada , Universidad de Navarra, Pamplona, Spain.

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.

PMID:
15102695
[Indexed for MEDLINE]
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