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Clinical Cancer Research Vol. 8, 3219-3225, October 2002
© 2002 American Association for Cancer Research

Experimental Therapeutics, Preclinical Pharmacology

Identification of an Antigenic Epitope for Helper T Lymphocytes from Carcinoembryonic Antigen1

Hiroya Kobayashi, Ryusuke Omiya, Marta Ruiz, Eduardo Huarte, Pablo Sarobe, Juan José Lasarte, Maite Herraiz, Bruno Sangro, Jesús Prieto, Francisco Borras-Cuesta and Esteban Celis2

Department of Pathology, Asahikawa Medical College, Asahikawa, Japan [H. K.]; Departamento de Medicina Interna, Facultad de Medicina, Universidad de Navarra, Pamplona, Spain [M. R., E. H., P. S., J. J. L., F. B-C.]; Departamento de Medicina Interna, Clínica Universitaria, Universidad de Navarra, 31008 Pamplona, Spain [M. H., B. S., J. P.]; and Department of Immunology, Mayo Clinic, Rochester, Minnesota 55905 [R. O., E. C.]

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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Copyright © 2002 by the American Association for Cancer Research.