Nanoparticulate vaccine inhibits tumor growth via improved T cell recruitment

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Nanoparticulate vaccine inhibits tumor growth via improved T cell recruitment

Terça, 04.12.2018

Este estudo descreve o desenvolvimento de uma vacina composta por nanopartículas e a caracterização da interacção desta imunoterapia com as células imunológicas alvo. Esta vacina induziu uma extensa infiltração de linfócitos T no tumor, e inibiu significativamente a progressão desta doença em modelos animais de melanoma e cancro da mama.

Eva Zupančič1,2,3, Caterina Curato2, Jung-Seok Kim‎2, Eilam Yeini4, Ziv Porat5, Ana S Viana6, Anat Globerson-Levin2,7, Tova Waks2,7, Zelig Eshhar 2,7, João N Moreira3,8, Ronit Satchi-Fainaro4, Lea Eisenbach2, Steffen Jung2, Helena F Florindo1*

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.

Nanomedicine: Nanotechnology, Biology and Medicine