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

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

In: Cancer Immunology, Immunotherapy, 2007, vol. 56, no. 11, p. 1795-1805

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    Titre
    • Immunogenicity of the carcinoembryonic antigen derived peptide 694 in HLA-A2 healthy donors and colorectal carcinoma patients
    Auteur
    • Alves, Pedro. Division of Clinical Onco-Immunology, Ludwig Institute for Cancer Research, Hôpital Orthopédique, HO-05, Rue Pierre-Decker, 4, 1005, Lausanne, Switzerland
    • Viatte, Sebastien. Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Epalinges, Switzerland
    • Fagerberg, Theres. Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Epalinges, Switzerland
    • Michielin, Olivier. Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Epalinges, Switzerland
    • Bricard, Gabriel. Division of Clinical Onco-Immunology, Ludwig Institute for Cancer Research, Hôpital Orthopédique, HO-05, Rue Pierre-Decker, 4, 1005, Lausanne, Switzerland
    • Bouzourene, Hanifa. Institut Universitaire de Pathologie, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
    • Vuilleumier, Henri. Department of Surgery, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
    • Kruger, Thorsten. Department of Surgery, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
    • Givel, Jean-Claude. Department of Surgery, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
    • Lévy, Frédéric. Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Epalinges, Switzerland
    • Speiser, Daniel. Division of Clinical Onco-Immunology, Ludwig Institute for Cancer Research, Hôpital Orthopédique, HO-05, Rue Pierre-Decker, 4, 1005, Lausanne, Switzerland
    • Cerottini, Jean-Charles. Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Epalinges, Switzerland
    • Romero, Pedro. Division of Clinical Onco-Immunology, Ludwig Institute for Cancer Research, Hôpital Orthopédique, HO-05, Rue Pierre-Decker, 4, 1005, Lausanne, Switzerland
    Type de document
    • Postprint
    Langue
    • Anglais
    Publié dans
    • Cancer Immunology, Immunotherapy, 2007, vol. 56, no. 11, p. 1795-1805. Springer-Verlag
    Autre version électronique
    Identifiant OAI-PMH
    • oai:doc.rero.ch:320431
    Summary
    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 CEA694-702 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