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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 >

Induction of multiepitopic and long-lasting immune responses against tumour antigens by immunization with peptides, DNA and recombinant adenoviruses expressing minigenes
Authors: Durantez, M. (Maika)
Lopez-Vazquez, A.B. (Ana B.)
Cerio, A.L.(A.L.) de
Huarte, E. (Eduardo)
Casares, N. (Noelia)
Prieto, J. (Jesús)
Borras-Cuesta, F. (Francisco)
Lasarte, J.J. (Juan José)
Sarobe, P. (Pablo)
Keywords: Antigens, Neoplasm/immunology
Cancer Vaccines/immunology
Epitopes, T-Lymphocyte
Peptides/immunology
Vaccines, DNA/immunology
Issue Date: 2009
Publisher: Blackwell
Publisher version: http://dx.doi.org/10.1111/j.1365-3083.2008.02202.x
ISSN: 0300-9475
Citation: Durantez M, Lopez-Vazquez AB, de Cerio AL, Huarte E, Casares N, Prieto J, et al. Induction of multiepitopic and long-lasting immune responses against tumour antigens by immunization with peptides, DNA and recombinant adenoviruses expressing minigenes. Scand J Immunol 2009 Feb;69(2):80-89.
Abstract
The development of immunization strategies to induce strong and multiepitopic T-cell responses against tumour antigens is needed for anti-tumour immunotherapy. However, a common finding after immunization with complex antigens is the preferential induction of immune responses against immunodominant epitopes. In this study, with the aim of inducing multiepitopic responses against several common tumour antigens, we have designed a minigene construct encoding four human leucocyte antigen (HLA)-A2-restricted epitopes belonging to tumour antigens CEA (CEA-691 and CEA-571), MAGE2 (MAGE2-157) and MAGE3 (MAGE3-112), as well as the universal PADRE epitope recognized by T helper lymphocytes. To optimize the activation of immune responses against these epitopes, we have used different antigen formats (short peptides encompassing individual epitopes and DNA plasmids or adenoviral constructs expressing the minigene) in single or combined immunization schedules. A single immunization with either DNA plasmid or recombinant adenovirus induced a monospecific immune response against the immunodominant epitope CEA-571, whereas immunization with the peptide pool induced responses against all epitopes. Combination of peptide priming followed by a boost with the plasmid and the recombinant adenovirus expressing the minigene induced stronger, multi-specific and long-lasting immune responses, overcoming the immunodominance imposed by the main T-cell epitope. Moreover, these combined immunization strategies were able to induce responses that were able to recognize Mel624 HLA-A2+ tumour cells expressing MAGE2. These results suggest that heterologous immunization strategies combining peptides and DNA or recombinant adenoviruses can be useful to broaden the specificity and enhance the efficacy of subunit vaccines.
Permanent link: http://hdl.handle.net/10171/20420
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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