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01-10-2009 | Original Article

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: Stéphanie Delluc, Patricia Hachem, Sylvie Rusakiewicz, Auguste Gaston, Carmen Marchiol-Fournigault, Lea Tourneur, Narjes Babchia, Didier Fradelizi, Armelle Regnault, Kim Hanh Le Quan Sang, Gilles Chiocchia, Agnès Buzyn

Published in: Cancer Immunology, Immunotherapy | Issue 10/2009

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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Title: 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: Stéphanie Delluc
Patricia Hachem
Sylvie Rusakiewicz
Auguste Gaston
Carmen Marchiol-Fournigault
Lea Tourneur
Narjes Babchia
Didier Fradelizi
Armelle Regnault
Kim Hanh Le Quan Sang
Gilles Chiocchia
Agnès Buzyn
Publication date: 01-10-2009
Publisher: Springer-Verlag
Published in: Cancer Immunology, Immunotherapy / Issue 10/2009
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-009-0678-7

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