Nanoparticulate vaccine inhibits tumor growth via improved T cell recruitment into melanoma and huHER2 breast cancer
Autor: | Eva Zupancic, Tova Waks, Ronit Satchi-Fainaro, Eilam Yeini, Ziv Porat, Anat Globerson-Levin, Caterina Curato, João Nuno Moreira, Steffen Jung, Lea Eisenbach, Ana S. Viana, Zelig Eshhar, Jung-Seok Kim, Helena F. Florindo |
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Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Carcinogenesis T cell Lymphocyte Biomedical Engineering Pharmaceutical Science Medicine (miscellaneous) Breast Neoplasms Bioengineering CD8-Positive T-Lymphocytes Lymphocyte Activation Cancer Vaccines Mice 03 medical and health sciences Immune system Tumor Cells Cultured medicine Animals Cytotoxic T cell General Materials Science Tumor microenvironment Tumor-infiltrating lymphocytes business.industry Dendritic cell Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure Cancer research Nanoparticles Molecular Medicine Female Cancer vaccine business T-Lymphocytes Cytotoxic |
Zdroj: | Nanomedicine: Nanotechnology, Biology and Medicine. 14:835-847 |
ISSN: | 1549-9634 |
DOI: | 10.1016/j.nano.2017.12.011 |
Popis: | Nanoparticulate vaccines are promising tools to overcome cancer immune evasion. However, a deeper understanding on nanoparticle-immune cell interactions and treatments regime is required for optimal efficacy. We provide a comprehensive study of treatment schedules and mode of antigen-association to nanovaccines on the modulation of T cell immunity in vivo, under steady-state and tumor-bearing mice. The coordinated delivery of antigen and two adjuvants (Monophosphoryl lipid A, oligodeoxynucleotide cytosine-phosphate-guanine motifs (CpG)) by nanoparticles was crucial for dendritic cell activation. A single vaccination dictated a 3-fold increase on cytotoxic memory-T cells and raised antigen-specific immune responses against B16.M05 melanoma. It generated at least a 5-fold increase on IFN-γ cytokine production, and presented over 50% higher lymphocyte count in the tumor microenvironment, compared to the control. The number of lymphocytes at the tumor site doubled with triple immunization. This lymphocyte infiltration pattern was confirmed in mammary huHER2 carcinoma, with significant tumor reduction. |
Databáze: | OpenAIRE |
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