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

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Serval ID
serval:BIB_9EF18CF1C772
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Immunogenicity of the carcinoembryonic antigen derived peptide 694 in HLA-A2 healthy donors and colorectal carcinoma patients.
Journal
Cancer immunology, immunotherapy
Author(s)
Alves P.M., Viatte S., Fagerberg T., Michielin O., Bricard G., Bouzourene H., Vuilleumier H., Kruger T., Givel J.C., Lévy F., Speiser D.E., Cerottini J.C., Romero P.
ISSN
0340-7004
Publication state
Published
Issued date
2007
Peer-reviewed
Oui
Volume
56
Number
11
Pages
1795-1805
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
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 CEA(694-702) 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 CEA(694-702) 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.
Keywords
Amino Acid Sequence, Antigen Presentation/immunology, CD8-Positive T-Lymphocytes/cytology, CD8-Positive T-Lymphocytes/immunology, Cancer Vaccines/therapeutic use, Carcinoembryonic Antigen/genetics, Carcinoembryonic Antigen/immunology, Carcinoma/therapy, Cell Line, Tumor, Cell Proliferation, Colorectal Neoplasms/immunology, Colorectal Neoplasms/therapy, HLA-A2 Antigen/metabolism, Humans, Leukocytes, Mononuclear/immunology, Lymphocyte Activation, Molecular Sequence Data, Peptide Fragments/genetics, Peptide Fragments/metabolism, Protein Binding
Pubmed
Web of science
Open Access
Yes
Create date
28/01/2008 12:17
Last modification date
01/10/2019 7:19
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