Novel immunomodulatory properties of low dose cytarabine entrapped in a mannosylated cationic liposome
| Autor: | Emilie Picard, Nya L. Fraleigh, Leila Mousavifar, Hoyun Lee, Graham Pawelec, Jordan D. Lewicky, Grace W. Ma, Hoang-Thanh Le, Alexandrine L. Martel, René Roy |
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| Rok vydání: | 2021 |
| Předmět: |
Cellular immunity
medicine.medical_treatment Pharmaceutical Science 02 engineering and technology CD8-Positive T-Lymphocytes 030226 pharmacology & pharmacy Immunomodulation Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Immune system Cancer immunotherapy Antigen medicine Animals Cationic liposome Immunity Cellular Tumor microenvironment Chemistry Cytarabine biochemical phenomena metabolism and nutrition 021001 nanoscience & nanotechnology Cytokine Liposomes Leukocytes Mononuclear Cancer research 0210 nano-technology Muramyl dipeptide |
| Zdroj: | International Journal of Pharmaceutics. 606:120849 |
| ISSN: | 0378-5173 |
| DOI: | 10.1016/j.ijpharm.2021.120849 |
| Popis: | Cancer treatment remains unsatisfactory with high rates of recurrence and metastasis. Immunomodulatory agents capable of promoting cellular antitumor immunity while inhibiting the local immunosuppressive tumor microenvironment could greatly improve cancer treatment. We have developed a multi-targeted mannosylated cationic liposome delivery system containing muramyl dipeptide (DS) and low doses of the chemotherapeutic agent cytarabine (Ara-C). Immunomodulation of primary immune cells and immortalized cancer cell lines by Ara-C/DS was assessed by measuring cytokine levels and surface marker expression. As a proof of concept, the generation of targeted cellular immunity was investigated in the context of responses to viral antigens. This report is the first demonstrating that Ara-C combined with DS can modulate immune responses and revert immunosuppression as evidenced by increased IFN-γ and IL-12p40 without changes in IL-10 in peripheral blood mononuclear cells, and increased CD80 and decreased CD163 on immunosuppressive macrophages. Furthermore, Ara-C/DS increased MHC class I expression on cancer cells while increasing the production of antigen-specific IFN-γ+ CD8+ T cells in viral peptide-challenged lymphocytes from both humans and vaccinated mice. Taken together, these results are the first to document immunomodulatory properties of Ara-C linked with recognition of antigens and potentially the generation of antitumor immune memory. |
| Databáze: | OpenAIRE |
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