Low dose gemcitabine-loaded lipid nanocapsules target monocytic myeloid-derived suppressor cells and potentiate cancer immunotherapy

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TitreLow dose gemcitabine-loaded lipid nanocapsules target monocytic myeloid-derived suppressor cells and potentiate cancer immunotherapy
Type de publicationArticle de revue
AuteurSasso, Maria Stella , Lollo, Giovanna , Pitorre, Marion , Solito, Samantha , Pinton, Laura , Valpione, Sara , Bastiat, Guillaume , Mandruzzato, Susanna , Bronte, Vincenzo , Marigo, Ilaria , Benoît, Jean-Pierre
PaysPays-Bas
EditeurElsevier
VilleAmsterdam
TypeArticle scientifique dans une revue à comité de lecture
Année2016
LangueAnglais
Date22 avril 2016
Pagination47-62
Volume96
Titre de la revueBiomaterials
ISSN0142-9612
Mots-clésAdoptive T cell therapy, Gemcitabine, Lipid nanocapsules, Myeloid-derived suppressor cells
Résumé en anglais

Tumor-induced expansion of myeloid-derived suppressor cells (MDSCs) is known to impair the efficacy of cancer immunotherapy. Among pharmacological approaches for MDSC modulation, chemotherapy with selected drugs has a considerable interest due to the possibility of a rapid translation to the clinic. However, such approach is poorly selective and may be associated with dose-dependent toxicities. In the present study, we showed that lipid nanocapsules (LNCs) loaded with a lauroyl-modified form of gemcitabine (GemC12) efficiently target the monocytic MDSC subset. Subcutaneous administration of GemC12-loaded LNCs reduced the percentage of spleen and tumor-infiltrating M-MDSCs in lymphoma and melanoma-bearing mice, with enhanced efficacy when compared to free gemcitabine. Consistently, fluorochrome-labeled LNCs were preferentially uptaken by monocytic cells rather than by other immune cells, in both tumor-bearing mice and human blood samples from healthy donors and melanoma patients. Very low dose administration of GemC12-loaded LNCs attenuated tumor-associated immunosuppression and increased the efficacy of adoptive T cell therapy. Overall, our results show that GemC12-LNCs have monocyte-targeting properties that can be useful for immunomodulatory purposes, and unveil new possibilities for the exploitation of nanoparticulate drug formulations in cancer immunotherapy.

URL de la noticehttp://okina.univ-angers.fr/publications/ua14603
DOI10.1016/j.biomaterials.2016.04.010
Titre abrégéBiomaterials