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Functional HLA-DR T cell epitopes of CEA identified in patients with colorectal carcinoma immunized with the recombinant protein CEA.
Department of Oncology, Radiology and Clinical Immunology, Section of Oncology, Uppsala University Hospital, Uppsala, Sweden. Department of Oncology and Cancer Centre Karolinska, Karolinska Hospital, Stockholm, Sweden.
Department of Oncology and Cancer Centre Karolinska, Karolinska Hospital, Stockholm, Sweden.
Department of Surgery, Huddinge University Hospital, Stockholm, Sweden.
Department of Oncology and Cancer Centre Karolinska, Karolinska Hospital, Stockholm, Sweden.
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2004 (English)In: Cancer Immunology and Immunotherapy, ISSN 0340-7004, E-ISSN 1432-0851, Vol. 53, no 4, 331-337 p.Article in journal (Refereed) Published
Abstract [en]

A baculovirus-produced recombinant CEA (rCEA) protein comprising the extracellular region was used for vaccination of CRC patients with or without GM-CSF as an adjuvant cytokine. Ten patients with a significant proliferative T cell response against rCEA were selected for T cell epitope mapping. Fifteen-aa-long overlapping peptides covering the entire aa sequence of the external domain of CEA were used in a proliferation assay. In six of the patients a repeatable T cell response against at least one peptide was demonstrated. For the first time, nine functional HLA-DR epitopes of CEA were defined. Two of the peptides were recognized by more than one patient, i.e., two and three patients, respectively. Those 15-mer peptides that induced a proliferative T cell response fitted to the actual HLA-DR type (SYFPEITHI). The affinity of the native peptides for the T cell receptor was in the low to intermediate range (scores 6-19). The 15-mer peptides also contained 9-mer peptide sequences that could be predicted to bind to the actual HLA-ABC genotypes (SYFPEITHI/BIMAS). Blocking experiments using monoclonal antibodies indicated that the proliferative T cell response was both MHC class I and II restricted. The defined HLA-DR T cell epitopes were spread over the entire CEA molecule, but a higher frequency was noted towards the C-terminal. Peptides with a dual specificity may form a basis for production of subunit cancer vaccines, but modifications should be done to increase the T cell affinity, thereby optimizing the antitumoral effects of the vaccine.

Place, publisher, year, edition, pages
2004. Vol. 53, no 4, 331-337 p.
Keyword [en]
T cell epitopes, Vaccination, HLA-DR, CEA
National Category
Surgery
Identifiers
URN: urn:nbn:se:umu:diva-126903DOI: 10.1007/s00262-003-0441-4PubMedID: 14605762OAI: oai:DiVA.org:umu-126903DiVA: diva2:1038821
Available from: 2016-10-20 Created: 2016-10-20 Last updated: 2016-10-20

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