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Dadun > Depósito Académico > CIMA (Centro de Investigación Médica Aplicada) > Área de Terapia génica y Hepatología > Inmunología hepatitis virales > DA - CIMA - Terapia génica y Hepatología - Inmunología hepatitis virales - Artículos de revista >

Enhancing immunogenicity of a CTL epitope from carcinoembryonic antigen by selective amino acid replacements
Authors: Huarte, E. (Eduardo)
Sarobe, P. (Pablo)
Lu, J. (Jun)
Casares, N. (Noelia)
Lasarte, J.J. (Juan José)
Dotor, J. (Javier)
Ruiz, M. (Marta)
Prieto, J. (Jesús)
Celis, E. (Esteban)
Borras-Cuesta, F. (Francisco)
Keywords: Carcinoembryonic Antigen/immunology
Epitopes/immunology
HLA-A2 Antigen/immunology
Peptide Fragments/immunology
Issue Date: 2002
Publisher: American Association for Cancer Research
Publisher version: http://clincancerres.aacrjournals.org/content/8/7/2336.long
ISSN: 1078-0432
Citation: Huarte E, Sarobe P, Lu J, Casares N, Lasarte JJ, Dotor J, et al. Enhancing immunogenicity of a CTL epitope from carcinoembryonic antigen by selective amino acid replacements. Clin Cancer Res 2002 Jul;8(7):2336-2344.
Abstract
PURPOSE: Many epitopes from tumor antigens recognized by CTLs canbe poorly immunogenic. This low immunogenicity can be improved by carrying out amino acid replacements in their sequence. We have applied this strategy to enhance the immunogenicity of the HLA-A2-restricted CTL epitope CEA691 (IMIGVLVGV) from carcinoembryonic antigen (CEA), which is expressed by a wide variety of tumors. EXPERIMENTAL DESIGN: Substituted peptides from CEA691 were synthesized and tested in HLA-A2-binding assays, and in recognition by CEA691-specific CTL. Selected peptides were used to induce CTL responses in vivo in HLA-A2Kb transgenic mice and in vitro with human cells. RESULTS: Our experiments afforded several peptides with enhanced binding and/or recognition by CTL specific of CEA691. However, when HLA-A2Kb mice were immunized with these peptides only a few induced a CTL response that cross-reacted with CEA691. Additional replacement of their NH(2)-terminal amino acid by Y (tyrosine) afforded peptides YMIGMLVGV and YMIGVLLGV with enhanced in vivo and in vitro immunogenicity than CEA691. Indeed, they activated a greater number of precursor cells that recognized CEA691-pulsed cells and tumor cells expressing CEA. CONCLUSIONS: Our results widen the possibility of treating CEA-expressing tumors with enhanced efficacy.
Permanent link: http://hdl.handle.net/10171/20616
Appears in Collections:DA - Medicina - Medicina Interna - Artículos de revista
DA - CIMA - Terapia génica y Hepatología - Inmunología experimental - Artículos de revista
DA - CIMA - Terapia génica y Hepatología - Inmunología hepatitis virales - Artículos de revista

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