TY - JOUR
T1 - Identification of an antigenic epitope for helper T lymphocytes from carcinoembryonic antigen
AU - Kobayashi, Hiroya
AU - Omiya, Ryusuke
AU - Ruiz, Marta
AU - Huarte, Eduardo
AU - Sarobe, Pablo
AU - Lasarte, Juan José
AU - Herraiz, Maite
AU - Sangro, Bruno
AU - Prieto, Jesús
AU - Borras-Cuesta, Francisco
AU - Celis, Esteban
PY - 2002/10/1
Y1 - 2002/10/1
N2 - Purpose: The product of the carcinoembryonic antigen (CEA) gene is an attractive candidate for T-cell-based immunotherapy because it is frequently expressed in epithelial solid carcinomas. Although many CEA peptide epitopes capable of stimulating CTLs have been identified, no MHC class II-restricted T helper epitope has yet been reported. Experimental Design: The amino acid sequence of CEA was examined for the presence of potential T helper epitopes, and candidate peptides were used to stimulate in vitro T-cell responses. Results: We describe here that using an algorithm to identify promiscuous helper T-cell epitopes, a peptide of CEA occupying residue positions 653 to 667 (CEA653-667), was effective in inducing in vitro T helper responses in the context of the HLA-DR4, HLA-DR7, and HLA-DR9 alleles. Most significantly, some of the peptide-reactive helper T lymphocytes were also capable of recognizing naturally processed antigen in the form of recombinant CEA protein or cell lysates from tumors that express CEA. Interestingly, the newly identified helper T-cell epitope was found to overlap with a previously described HLA-A24-restricted CTL epitope, CEA652-660, which could facilitate the development of a therapeutic vaccine capable of eliciting both CTL and T helper responses in patients suffering from epithelial carcinomas. Conclusion: These results indicate that T helper lymphocytes are capable of recognizing CEA as a tumor antigen and that epitope CEA653-667 could be used for immunotherapy against tumors expressing CEA.
AB - Purpose: The product of the carcinoembryonic antigen (CEA) gene is an attractive candidate for T-cell-based immunotherapy because it is frequently expressed in epithelial solid carcinomas. Although many CEA peptide epitopes capable of stimulating CTLs have been identified, no MHC class II-restricted T helper epitope has yet been reported. Experimental Design: The amino acid sequence of CEA was examined for the presence of potential T helper epitopes, and candidate peptides were used to stimulate in vitro T-cell responses. Results: We describe here that using an algorithm to identify promiscuous helper T-cell epitopes, a peptide of CEA occupying residue positions 653 to 667 (CEA653-667), was effective in inducing in vitro T helper responses in the context of the HLA-DR4, HLA-DR7, and HLA-DR9 alleles. Most significantly, some of the peptide-reactive helper T lymphocytes were also capable of recognizing naturally processed antigen in the form of recombinant CEA protein or cell lysates from tumors that express CEA. Interestingly, the newly identified helper T-cell epitope was found to overlap with a previously described HLA-A24-restricted CTL epitope, CEA652-660, which could facilitate the development of a therapeutic vaccine capable of eliciting both CTL and T helper responses in patients suffering from epithelial carcinomas. Conclusion: These results indicate that T helper lymphocytes are capable of recognizing CEA as a tumor antigen and that epitope CEA653-667 could be used for immunotherapy against tumors expressing CEA.
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M3 - Article
C2 - 12374692
AN - SCOPUS:0036793872
SN - 1078-0432
VL - 8
SP - 3219
EP - 3225
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 10
ER -