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Dramatic efficacy improvement of a DC-based vaccine against AML by CD25 T cell depletion allowing the induction of a long-lasting T cell response.

Authors
  • Delluc, Stéphanie
  • Hachem, Patricia
  • Rusakiewicz, Sylvie
  • Gaston, Auguste
  • Marchiol-Fournigault, Carmen
  • Tourneur, Lea
  • Babchia, Narjes
  • Fradelizi, Didier
  • Regnault, Armelle
  • Sang, Kim Hanh Le Quan
  • Chiocchia, Gilles
  • Buzyn, Agnès
Type
Published Article
Journal
Cancer Immunology Immunotherapy
Publisher
Springer-Verlag
Publication Date
Oct 01, 2009
Volume
58
Issue
10
Pages
1669–1677
Identifiers
DOI: 10.1007/s00262-009-0678-7
PMID: 19225777
Source
Medline
License
Unknown

Abstract

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.

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