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

Maria Stella Sasso, Giovanna Lollo, Marion Pitorre, Samantha Solito, Laura Pinton, Sara Valpione, Guillaume Bastiat, Susanna Mandruzzato, Vincenzo Bronte, Ilaria Marigo, Jean Pierre Benoit

Research output: Contribution to journalArticlepeer-review

Abstract

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 (M - ) 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.

Original languageEnglish
Pages (from-to)47-62
Number of pages16
JournalBiomaterials
Volume96
DOIs
Publication statusPublished - Jul 1 2016

Keywords

  • Adoptive T cell therapy
  • Gemcitabine
  • Lipid nanocapsules
  • Myeloid-derived suppressor cells

ASJC Scopus subject areas

  • Biomaterials
  • Bioengineering
  • Ceramics and Composites
  • Mechanics of Materials
  • Biophysics

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