Identification of an antigenic epitope for helper T lymphocytes from carcinoembryonic antigen

Hiroya Kobayashi, Ryusuke Omiya, Marta Ruiz, Eduardo Huarte, Pablo Sarobe, Juan José Lasarte, Maite Herraiz, Bruno Sangro, Jesús Prieto, Francisco Borras-Cuesta, Esteban Celis

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49 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3219-3225
Number of pages7
JournalClinical Cancer Research
Volume8
Issue number10
StatePublished - Oct 1 2002

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Kobayashi, H., Omiya, R., Ruiz, M., Huarte, E., Sarobe, P., Lasarte, J. J., Herraiz, M., Sangro, B., Prieto, J., Borras-Cuesta, F., & Celis, E. (2002). Identification of an antigenic epitope for helper T lymphocytes from carcinoembryonic antigen. Clinical Cancer Research, 8(10), 3219-3225.