Low dose gemcitabine-loaded lipid nanocapsules target monocytic myeloid-derived suppressor cells and potentiate cancer immunotherapy
| Autor: | Giovanna Lollo, Vincenzo Bronte, Guillaume Bastiat, Samantha Solito, Laura Pinton, Susanna Mandruzzato, Marion Pitorre, Ilaria Marigo, Sara Valpione, Jean-Pierre Benoit, Maria Stella Sasso |
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| Přispěvatelé: | Universita degli Studi di Padova, Micro et Nanomédecines Biomimétiques, Université Bretagne Loire (UBL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université d'Angers (UA), Veneto Institute of Oncology, IOV - IRCCS, Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Bretagne Loire (UBL), Micro et Nanomédecines Biomimétiques (MINT) |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
T-Lymphocytes medicine.medical_treatment [SDV]Life Sciences [q-bio] Pharmacology Deoxycytidine Immunotherapy Adoptive Monocytes Lipid nanocapsules Cancer immunotherapy Neoplasms Adoptive T cell therapy Gemcitabine Myeloid-derived suppressor cells Medicine Cell Death Melanoma Biomaterials Bioengineering Ceramics and Composites Mechanics of Materials Biophysics Lipids 3. Good health medicine.anatomical_structure Immunotherapy medicine.drug T cell Mice Transgenic Drug Administration Schedule 03 medical and health sciences Immune system Nanocapsules Animals Humans Immunosuppression Therapy Chemotherapy Dose-Response Relationship Drug business.industry medicine.disease Mice Inbred C57BL 030104 developmental biology Myeloid-derived Suppressor Cell Pinocytosis business Spleen |
| Zdroj: | Biomaterials Biomaterials, Elsevier, 2016, 96, pp.47-62. ⟨10.1016/j.biomaterials.2016.04.010⟩ |
| ISSN: | 0142-9612 |
| Popis: | International audience; 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. |
| Databáze: | OpenAIRE |
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