4.6 Article

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

Journal

NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
Volume 14, Issue 3, Pages 835-847

Publisher

ELSEVIER
DOI: 10.1016/j.nano.2017.12.011

Keywords

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

Funding

  1. Fundacao para a Ciencia e a Technologia-Ministerio da Ciencia, Tecnologia e Ensino Superior (FCT-MCTES), Portugal [SFRH/BD/78480/2011, UTAP-ICDT/DTP-FTO/0016/2014, SAICTPAC/0019/2015, UID/DTP/04138/2013]
  2. The Israeli Ministry of Health
  3. FCT-MCTES [ENMed/0051/2016]
  4. European Research Council (ERC) [340345, 617445]
  5. EMBO [ASTF 277-2015]

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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-gamma 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. (c) 2018 Elsevier Inc. All rights reserved.

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