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Viral-mimicking protein nanoparticle vaccine for eliciting anti-tumor responses

Paper ID Volume ID Publish Year Pages File Format Full-Text
5435 384 2016 9 PDF Available
Title
Viral-mimicking protein nanoparticle vaccine for eliciting anti-tumor responses
Abstract

The immune system is a powerful resource for the eradication of cancer, but to overcome the low immunogenicity of tumor cells, a sufficiently strong CD8+ T cell-mediated adaptive immune response is required. Nanoparticulate biomaterials represent a potentially effective delivery system for cancer vaccines, as they can be designed to mimic viruses, which are potent inducers of cellular immunity. We have been exploring the non-viral pyruvate dehydrogenase E2 protein nanoparticle as a biomimetic platform for cancer vaccine delivery. Simultaneous conjugation of a melanoma-associated gp100 epitope and CpG to the E2 nanoparticle (CpG-gp-E2) yielded an antigen-specific increase in the CD8+ T cell proliferation index and IFN-γ secretion by 1.5-fold and 5-fold, respectively, compared to an unbound peptide and CpG formulation. Remarkably, a single nanoparticle immunization resulted in a 120-fold increase in the frequency of melanoma epitope-specific CD8+ T cells in draining lymph nodes and a 30-fold increase in the spleen, relative to free peptide with free CpG. Furthermore, in the very aggressive B16 melanoma murine tumor model, prophylactic immunization with CpG-gp-E2 delayed the onset of tumor growth by approximately 5.5 days and increased animal survival time by approximately 40%, compared to PBS-treated animals. These results show that by combining optimal particle size and simultaneous co-delivery of molecular vaccine components, antigen-specific anti-tumor immune responses can be significantly increased.

Keywords
Protein nanoparticle; T cells; CD8; Biomimetic; Tumor-associated antigen; Vaccine
First Page Preview
Viral-mimicking protein nanoparticle vaccine for eliciting anti-tumor responses
Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 86, April 2016, Pages 83–91
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering