TY - JOUR
T1 - Identification and Characterization of A T-Helper Peptide from Carcinoembryonic Antigen
AU - Ruiz, Marta
AU - Kobayashi, Hiroya
AU - Lasarte, Juan José
AU - Prieto, Jesús
AU - Borrás-Cuesta, Francisco
AU - Celis, Esteban
AU - Sarobe, Pablo
PY - 2004/4/15
Y1 - 2004/4/15
N2 - 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.
AB - 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.
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U2 - 10.1158/1078-0432.CCR-03-0476
DO - 10.1158/1078-0432.CCR-03-0476
M3 - Article
C2 - 15102695
AN - SCOPUS:1942438127
SN - 1078-0432
VL - 10
SP - 2860
EP - 2867
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 8
ER -