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Nanomedicine. 2018 Apr;14(3):835-847. doi: 10.1016/j.nano.2017.12.011. Epub 2018 Jan 3.

Nanoparticulate vaccine inhibits tumor growth via improved T cell recruitment into melanoma and huHER2 breast cancer.

Author information

1
Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal; Department of Immunology, Weizmann Institute of Science, Rehovot, Israel; Center for Neuroscience and Cell Biology (CNC), University of Coimbra, Faculty of Medicine (Polo I), Coimbra, Portugal.
2
Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
3
Department of Physiology and Pharmacology, Sackler School of Medicine, Room 607, Tel Aviv University, Tel Aviv, Israel.
4
Flow Cytometry unit, Biological Services Department, Weizmann Institute of Science, Rehovot, Israel.
5
Chemistry and Biochemistry Center, Sciences Faculty, Universidade de Lisboa, Lisbon, Portugal.
6
Department of Immunology, Weizmann Institute of Science, Rehovot, Israel; Immunology research center, Tel Aviv Sourasky Medical Center (TASMC), Tel Aviv, Israel.
7
Center for Neuroscience and Cell Biology (CNC), University of Coimbra, Faculty of Medicine (Polo I), Coimbra, Portugal; Faculty of Pharmacy (FFUC), University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, Coimbra, Portugal.
8
Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal. Electronic address: hflorindo@ff.ul.pt.

Abstract

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.

KEYWORDS:

Breast cancer; Cancer vaccine; Cytotoxic T cells; Melanoma; Tumor-infiltrating lymphocytes

PMID:
29306001
DOI:
10.1016/j.nano.2017.12.011
[Indexed for MEDLINE]

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