Functional HLA-DR T cell epitopes of CEA identified in patients with colorectal carcinoma immunized with the recombinant protein CEA.

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Ullenhag, Gustav JDepartment 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 (författare)

Functional HLA-DR T cell epitopes of CEA identified in patients with colorectal carcinoma immunized with the recombinant protein CEA.

Artikel/kapitelEngelska2004

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Springer Science and Business Media LLC,2004
printrdacarrier

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LIBRIS-ID:oai:DiVA.org:umu-126903
https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-126903URI
https://doi.org/10.1007/s00262-003-0441-4DOI
http://kipublications.ki.se/Default.aspx?queryparsed=id:1940647URI

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Språk:engelska
Sammanfattning på:engelska

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Ämneskategori:art swepub-publicationtype

Anmärkningar

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.

Ämnesord och genrebeteckningar

MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Kirurgi hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Surgery hsv//eng
T cell epitopes
Vaccination
HLA-DR
CEA

Biuppslag (personer, institutioner, konferenser, titlar ...)

Fagerberg, JanDepartment of Oncology and Cancer Centre Karolinska, Karolinska Hospital, Stockholm, Sweden (författare)
Strigård, KarinKarolinska Institutet(Swepub:umu)Kast0065 (författare)
Frödin, Jan-ErikKarolinska Institutet (författare)
Mellstedt, HåkanKarolinska Institutet (författare)
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, SwedenDepartment of Oncology and Cancer Centre Karolinska, Karolinska Hospital, Stockholm, Sweden (creator_code:org_t)

Sammanhörande titlar

Ingår i:Cancer Immunology and Immunotherapy: Springer Science and Business Media LLC53:4, s. 331-3370340-70041432-0851

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Cancer Immunology and Immunotherapy (Sök värdpublikationen i LIBRIS)

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Av författaren/redakt...: Ullenhag, Gustav ...; Fagerberg, Jan; Strigård, Karin; Frödin, Jan-Erik; Mellstedt, Håkan

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MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Klinisk medicin; och Kirurgi

Artiklar i publikationen: Cancer Immunolog ...

Av lärosätet: Umeå universitet; Karolinska Institutet

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