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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

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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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Acknowledgments

This work was supported by the “Institut National de la Santé et de la Recherche Médicale” (INSERM). The laboratory is associated to the “Ligue contre le cancer”, Comité Ile de France. S. Delluc received a financial support from France Intergroupe de la Leucemie Myeloide Chronique (FI LMC) and the “Delegation Regionale à la Recherche Clinique (DRRC)”.

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Authors and Affiliations

  1. Département d’Immunologie, Institut Cochin, Institut National de la Santé Et de la Recherche Médicale (INSERM) U 567, Centre National de Recherche Scientifique (CNRS) UMR 8104, Institut Fédératif de Recherche (IFR) 116, Université René Descartes, Paris V, France

    Stéphanie Delluc, Auguste Gaston, Carmen Marchiol-Fournigault, Lea Tourneur, Narjes Babchia, Didier Fradelizi & Gilles Chiocchia

  2. EA4054, ENVA, Maisons-Alfort, Université René Descartes, Paris V, France

    Patricia Hachem, Sylvie Rusakiewicz & Agnès Buzyn

  3. Unite U462, INSERM-Universite Paris VII, Hopital Saint-Louis–Institut Universitaire d’Hematologie, Paris, France

    Armelle Regnault

  4. Service de Pharmacologie, Hôpital Necker-Enfants Malades, Assistance Publique des Hôpitaux de Paris (AP-HP), Paris, France

    Kim Hanh Le Quan Sang

  5. Service d’Hématologie Adultes, Hôpital Necker-Enfants Malades, AP-HP, 149 rue de Sèvres, 75743, Paris Cedex 15, France

    Agnès Buzyn

Authors
  1. Stéphanie Delluc
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  2. Patricia Hachem
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  3. Sylvie Rusakiewicz
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  4. Auguste Gaston
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  5. Carmen Marchiol-Fournigault
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  6. Lea Tourneur
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  7. Narjes Babchia
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  9. Armelle Regnault
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  10. Kim Hanh Le Quan Sang
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  11. Gilles Chiocchia
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  12. Agnès Buzyn
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Correspondence to Agnès Buzyn.

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Delluc, S., Hachem, P., Rusakiewicz, S. et al. 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. Cancer Immunol Immunother 58, 1669–1677 (2009). https://doi.org/10.1007/s00262-009-0678-7

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