Immunogenicity of the carcinoembryonic antigen derived peptide 694 in HLA-A2 healthy donors and colorectal carcinoma patients

Pedro M S Alves, Sebastien Viatte, Theres Fagerberg, Olivier Michielin, Gabriel Bricard, Hanifa Bouzourene, Henri Vuilleumier, Thorsten Kruger, Jean Claude Givel, Frédéric Lévy, Daniel E. Speiser, Jean Charles Cerottini, Pedro Romero

    Research output: Contribution to journalArticlepeer-review


    Carcinoembryonic antigen (CEACAM5) is commonly overexpressed in human colon cancer. Several antigenic peptides recognized by cytolytic CD8+ T-cells have been identified and used in colon cancer phase-I vaccination clinical trials. The HLA-A*0201-binding CEA694-702 peptide was recently isolated from acid eluted MHC-I associated peptides from a human colon tumor cell line. However, the immunogenicity of this peptide in humans remains unknown. We found that the peptide CEA694-702 binds weakly to HLA-A*0201 molecules and is ineffective at inducing specific CD8+ T-cell responses in healthy donors. Immunogenic-altered peptide ligands with increased affinity for HLA-A*0201 were identified. Importantly, the elicited cytolytic T lymphocyte (CTL) lines and clones cross-reacted with the wild-type CEA 694-702 peptide. Tumor cells expressing CEA were recognized in a peptide and HLA-A*0201 restricted fashion, but high-CEA expression levels appear to be required for CTL recognition. Finally, CEA-specific T-cell precursors could be readily expanded by in vitro stimulation of peripheral blood mononuclear cell (PBMC) from colon cancer patients with altered CEA peptide. However, the CEA-specific CD8+ T-cell clones derived from cancer patients revealed low-functional avidity and impaired tumor-cell recognition. Together, using T-cells to demonstrate the processing and presentation of the peptide CEA694-702, we were able to corroborate its presentation by tumor cells. However, the low avidity of the specific CTLs generated from cancer patients as well as the high-antigen expression levels required for CTL recognition pose serious concerns for the use of CEA694-702 in cancer immunotherapy. © 2007 Springer-Verlag.
    Original languageEnglish
    Pages (from-to)1795-1805
    Number of pages10
    JournalCancer Immunology, Immunotherapy
    Issue number11
    Publication statusPublished - Nov 2007


    • Cancer vaccines
    • CTL
    • Tetramers
    • Tumor immunology


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