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Cancer Immunol Immunother ; 58(10): 1669-77, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19225777

RESUMO

Dendritic cell (DC)-based vaccination is a promising approach to enhance anti-tumor immunity that could be considered for acute myeloid leukemia (AML) patients with high-risk of relapse. Our purpose was to study the efficiency and to optimize the immunogenicity of a DC-based vaccine in a preclinical AML murine model. In this report, C57BL6 mice were vaccinated with DC pulsed with peptides eluted (EP) from the syngeneic C1498 myelomonocytic leukemic cell line in a prophylactic setting. In this model, a natural antileukemic immunity mediated by NK cells was observed in the control unloaded DC-vaccinated group. On the other hand, we showed that the cytotoxic antileukemic immune response induced by vaccination with eluted peptides pulsed-DC (DC/EP), in vitro and in vivo, was mainly mediated by CD4(+) T cells. Treatment with anti-CD25 antibody to deplete CD4(+) CD25(+) regulatory T cells before DC-vaccination dramatically improved the antileukemic immune response induced by immunization, and allowed the development of long-lasting immune responses that were tumor protective after a re-challenge with leukemic cells. Our results suggest that this approach could be successful against weakly immunogenic tumors such as AML, and could be translated in human.


Assuntos
Vacinas Anticâncer/imunologia , Células Dendríticas/imunologia , Leucemia Mieloide Aguda/imunologia , Leucemia Mieloide Aguda/terapia , Linfócitos T/imunologia , Animais , Anticorpos Monoclonais/imunologia , Feminino , Subunidade alfa de Receptor de Interleucina-2/metabolismo , Leucemia Mieloide Aguda/patologia , Depleção Linfocítica , Camundongos , Camundongos Endogâmicos C57BL , Taxa de Sobrevida , Linfócitos T/patologia , Vacinação
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