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

被引：33

作者：

Delluc, Stephanie ^{[5
]}

Hachem, Patricia ^{[4
]}

Rusakiewicz, Sylvie ^{[4
]}

Gaston, Auguste ^{[5
]}

Marchiol-Fournigault, Carmen ^{[5
]}

Tourneur, Lea ^{[5
]}

Babchia, Narjes ^{[5
]}

Fradelizi, Didier ^{[5
]}

Regnault, Armelle ^{[3
]}

Sang, Kim Hanh Le Quan ^{[2
]}

Chiocchia, Gilles ^{[5
]}

Buzyn, Agnes ^{[1
,4
]}

机构：

[1] Hop Necker Enfants Malad, AP HP, Serv Hematol Adultes, F-75743 Paris 15, France

[2] Hop Necker Enfants Malad, AP HP, Serv Pharmacol, F-75743 Paris 15, France

[3] Univ Paris 07, INSERM, U462, Hop St Louis,Inst Univ Hematol, Paris, France

[4] Univ Paris 05, EA4054, ENVA, Paris V, France

[5] Univ Paris 05, CNRS, Dept Immunol,UMR 8104, INSERM,U567,Inst Cochin,IFR 116, F-75270 Paris, France

来源：

CANCER IMMUNOLOGY IMMUNOTHERAPY | 2009年 / 58卷 / 10期

关键词：

Leukemia; Immunotherapy; DC-vaccination; Eluted peptides; Regulatory T cells; ACUTE MYELOID-LEUKEMIA; TUMOR-IMMUNITY; ANTITUMOR IMMUNITY; PEPTIDE; CD4(+); CD8(+); ELICIT; LYMPHOCYTES; STRATEGIES; REJECTION;

D O I：

10.1007/s00262-009-0678-7

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

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.

引用

页码：1669 / 1677

页数：9

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