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
Rok vydání: 2018
Předmět:
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