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* ERM-0208 Institut National de la Santé et de la Recherche Médicale, Faculté Kremlin Bicêtre, Institut Gustave Roussy, Villejuif, France;
Department of Hepatogastroenterology, Groupe Hospitalier Pitié Salpétrière,
Unité Institut National de la Santé et de la Recherche Médicale 517, Faculté de Médecine, Dijon, France;
Department of Neurology, Groupe Hospitalier Pitié Salpétrière, Paris, France;
¶ Department of Biotherapies, Groupe Hospitalier Pitié-Salpétrière, Unité Mixte de Recherche 7087, Paris, France; and
|| Institut Pasteur, Unité d’Immunologie Cellulaire Antivirale, Paris, France
Dendritic cell-derived exosomes (DEX) are nanomeric vesicles harboring MHC/peptide complexes capable of promoting primary T cell responses and tumor rejection in the presence of adjuvants. In this study, we show that, in the absence of adjuvants, DEX mediate potent Ag-dependent antitumor effects against preestablished tumors in mice pretreated with immunopotentiating dosing of cyclophosphamide. Cyclophosphamide could 1) abolish the suppressive function of CD4+CD25+Foxp3+ regulatory T cells, 2) markedly enhance the magnitude of secondary but not primary CTL responses induced by DEX vaccines, 3) synergize with DEX in therapy but not prophylaxis tumor models. Therefore, therapeutic vaccines such as DEX aimed at boosting tumor-primed effector T cells could benefit procedures that minimize the effects of CD4+CD25+ regulatory T cells.
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