Chemoimmunotherapy of Tumors: Cyclophosphamide Synergizes with Exosome Based Vaccines

Julien Taieb; Nathalie Chaput; Noël Schartz; Stéphan Roux; Sophie Novault; Cédric Ménard; François Ghiringhelli; Magali Terme; Antoine Carpentier; Guillaume Darrasse-Jèse; François Lemonnier; Laurence Zitvogel

doi:10.4049/jimmunol.176.5.2722

Journal articles

Chemoimmunotherapy of Tumors: Cyclophosphamide Synergizes with Exosome Based Vaccines

Julien Taieb ^{1, 2, 3} Nathalie Chaput ^{1, 2} Noël Schartz ^{1, 2} Stéphan Roux ^{1, 2} Sophie Novault ^{1, 2} Cédric Ménard ^{1, 2} François Ghiringhelli ^{1, 2, 4} Magali Terme ^{1, 2} Antoine Carpentier ⁵ Guillaume Darrasse-Jèse ⁶ François Lemonnier ⁷ Laurence Zitvogel ^{1, 2, *}

* Corresponding author

1 INSERM - Institut National de la Santé et de la Recherche Médicale

2 IGR - Institut Gustave Roussy

3 Service d'Hépato-Gastro-Entérologie [CHU Pitié-Salpêtrière]

4 Mort cellulaire et cancer

5 Service de Neurologie [CHU Pitié-Salpêtrière]

6 BTPI - Biologie et thérapeutique des pathologies immunitaires

7 Immunité Cellulaire Antivirale

Abstract : 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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Journal articles

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Life Sciences [q-bio]

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https://hal-pasteur.archives-ouvertes.fr/pasteur-03360098
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Submitted on : Thursday, September 30, 2021 - 3:47:05 PM
Last modification on : Friday, January 7, 2022 - 3:30:02 PM

Chemoimmunotherapy of Tumors: Cyclophosphamide Synergizes with Exosome Based Vaccines

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Chemoimmunotherapy of Tumors: Cyclophosphamide Synergizes with Exosome Based Vaccines

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