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.
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.
Delluc
Stéphanie
S
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, Université René Descartes, Paris V, France.
Hachem
Patricia
P
Rusakiewicz
Sylvie
S
Gaston
Auguste
A
Marchiol-Fournigault
Carmen
C
Tourneur
Lea
L
Babchia
Narjes
N
Fradelizi
Didier
D
Regnault
Armelle
A
Sang
Kim Hanh Le Quan
KH
Chiocchia
Gilles
G
Buzyn
Agnès
A
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D015470:Leukemia, Myeloid, Acute / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D008212:Lymphocyte Depletion; D051379:Mice; D008810:Mice, Inbred C57BL; D015996:Survival Rate; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D014611:Vaccination
D000911:Antibodies, Monoclonal; D019496:Cancer Vaccines; D053645:Interleukin-2 Receptor alpha Subunit