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  Identification and characterization of Mcl-1- and cyclin B1-derived CTL epitopes
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 Ophav:
Andersen, Rikke Sick1, Forfatter
Straten, Per Thor1, Vejleder
Andersen, Mads Hald1, Vejleder
Aasted, Bent1, Vejleder
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1Det Biovidenskabelige Fakultet, København, Danmark, diskurs:18              
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 Abstract: Cytotoxic T lymphocytes (CTLs) are able to recognize peptides derived from tumor associated antigens (TAAs) in context of HLA molecules. TAA-derived peptides can be used in vaccines, and clinical trials with cancer patients have in some cases been promising. Therefore, substantial efforts have been invested in identifying TAAs and characterizing the CTLs recognizing these. The objective of this study was to identify and characterize HLA-A2-restricted CTL epitopes derived from the proteins myeloid cell leukemia-1 (Mcl-1) and cyclin B1. This was done by selecting a number of peptides derived from the two proteins using in silico prediction algorithms. Blood from cancer patients was screened for T cell responses against the peptides in an IFN-? ELISPOT assay. In addition, the peptides were analyzed for their HLA-A2 binding affinity using the Assembly assay. Subsequently, CTL clones were established by dendritic cell stimulations and limiting dilution. The clones were tested for cytotoxicity in a 51Cr-release assay.Nine Mcl-1-derived peptides were investigated. One of these, Mcl-1(139), elicited spontaneous responses in cancer patients, and a Mcl-1(139) specific CTL clone was able to lyse ex vivo enriched AML blasts, from an HLA-A2 positive acute myeloid leukemia patient, in an HLA-A2-restricted and peptide specific manner. Twelve cyclin B1-derived peptides were selected. Two of these, CB9(204) and CB10(203), elicited powerful and frequent spontaneous responses in cancer patients. However, CB9(204) also elicited powerful and frequent responses in healthy donors. CB10(203) specific CTL clones were established, and one of these were able to lyse two melanoma cancer cell lines. HLA class I-restriction experiments were, however, not convincing, indicating only partially HLA class I-restriction. Furthermore, two cold target inhibition assays showed differing results, indicating that not a single CTL clone, but at least two clones, were responsible for the observed lysis. Further investigations are needed.
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Basal

Bogmærk denne post: https://diskurs.kb.dk/item/diskurs:28070:2
 Type: Speciale
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Detaljer

Sprog: English - eng
 Datoer: 2008
 Sider: 105 pages
 Publiceringsinfo: København, Danmark : Institut for Veterinær Patobiologi
 Indholdsfortegnelse: -
 Note: Biology - Biotechnology, Biologi - Bioteknologi
 Type: Speciale
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