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Immunogenicity of the carcinoembryonic antigen derived peptide 694 in HLA-A2 healthy donors and colorectal carcinoma patients.
Cancer Immunol Immunother. 2007 Nov; 56(11):1795-805.CI

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.

Authors+Show Affiliations

Division of Clinical Onco-Immunology, Ludwig Institute for Cancer Research, Hôpital Orthopédique, HO-05, Rue Pierre-Decker, 4, 1005, Lausanne, Switzerland. Pedro.romero@isrec.unil.chNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17447064

Citation

Alves, Pedro M S., et al. "Immunogenicity of the Carcinoembryonic Antigen Derived Peptide 694 in HLA-A2 Healthy Donors and Colorectal Carcinoma Patients." Cancer Immunology, Immunotherapy : CII, vol. 56, no. 11, 2007, pp. 1795-805.
Alves PM, Viatte S, Fagerberg T, et al. Immunogenicity of the carcinoembryonic antigen derived peptide 694 in HLA-A2 healthy donors and colorectal carcinoma patients. Cancer Immunol Immunother. 2007;56(11):1795-805.
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. (2007). Immunogenicity of the carcinoembryonic antigen derived peptide 694 in HLA-A2 healthy donors and colorectal carcinoma patients. Cancer Immunology, Immunotherapy : CII, 56(11), 1795-805.
Alves PM, et al. Immunogenicity of the Carcinoembryonic Antigen Derived Peptide 694 in HLA-A2 Healthy Donors and Colorectal Carcinoma Patients. Cancer Immunol Immunother. 2007;56(11):1795-805. PubMed PMID: 17447064.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Immunogenicity of the carcinoembryonic antigen derived peptide 694 in HLA-A2 healthy donors and colorectal carcinoma patients. AU - Alves,Pedro M S, AU - Viatte,Sebastien, AU - Fagerberg,Theres, AU - Michielin,Olivier, AU - Bricard,Gabriel, AU - Bouzourene,Hanifa, AU - Vuilleumier,Henri, AU - Kruger,Thorsten, AU - Givel,Jean-Claude, AU - Lévy,Frédéric, AU - Speiser,Daniel E, AU - Cerottini,Jean-Charles, AU - Romero,Pedro, Y1 - 2007/04/20/ PY - 2007/01/29/received PY - 2007/03/23/accepted PY - 2007/4/21/pubmed PY - 2007/10/27/medline PY - 2007/4/21/entrez SP - 1795 EP - 805 JF - Cancer immunology, immunotherapy : CII JO - Cancer Immunol. Immunother. VL - 56 IS - 11 N2 - 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. SN - 0340-7004 UR - https://www.unboundmedicine.com/medline/citation/17447064/Immunogenicity_of_the_carcinoembryonic_antigen_derived_peptide_694_in_HLA_A2_healthy_donors_and_colorectal_carcinoma_patients_ L2 - https://dx.doi.org/10.1007/s00262-007-0323-2 DB - PRIME DP - Unbound Medicine ER -