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

Eva Zupančič, Caterina Curato, Jung Seok Kim, Eilam Yeini, Ziv Porat, Ana S. Viana, Anat Globerson-Levin, Tova Waks, Zelig Eshhar, João N. Moreira, Ronit Satchi-Fainaro, Lea Eisenbach, Steffen Jung, Helena F. Florindo*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)835-847
Number of pages13
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Volume14
Issue number3
DOIs
StatePublished - Apr 2018

Keywords

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

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