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

Authors
  • Molino, Nicholas M1
  • Neek, Medea1
  • Tucker, Jo Anne2
  • Nelson, Edward L3
  • Wang, Szu-Wen4
  • 1 Department of Chemical Engineering and Materials Science, University of California, Irvine, CA 92697, USA.
  • 2 Department of Medicine, University of California, Irvine, CA 92697, USA.
  • 3 Department of Medicine, University of California, Irvine, CA 92697, USA; Chao Family Comprehensive Cancer Center, University of California, Irvine, CA 92697, USA; Institute for Immunology, University of California, Irvine, CA 92697, USA.
  • 4 Department of Chemical Engineering and Materials Science, University of California, Irvine, CA 92697, USA; Chao Family Comprehensive Cancer Center, University of California, Irvine, CA 92697, USA; Department of Biomedical Engineering, University of California, Irvine, CA 92697, USA. Electronic address: [email protected]
Type
Published Article
Journal
Biomaterials
Publication Date
Apr 01, 2016
Volume
86
Pages
83–91
Identifiers
DOI: 10.1016/j.biomaterials.2016.01.056
PMID: 26894870
Source
Medline
Keywords
Language
English
License
Unknown

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. Copyright © 2016 Elsevier Ltd. All rights reserved.

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