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Virus-like particles and α-galactosylceramide form a self-adjuvanting composite particle that elicits anti-tumor responses.

Abstract
Virus-like particles (VLP) are effective vehicles for delivery of heterologous antigen to antigen-presenting cells. However VLP alone are insufficiently stimulatory to generate the signals required to facilitate effective priming of naïve T cells. We show that the VLP derived from rabbit hemorrhagic disease virus can bind the galactose-containing adjuvant α-galactosylceramide to form a composite particle for co-delivery of antigen and adjuvant to the same antigen-presenting cell. Vaccination with VLP and α-galactosylceramide activated splenic iNKT cells to produce IFN-γ and IL-4, led to the generation of antigen-specific T cells that protected prophylactically against subcutaneous tumor challenge, and was more effective at generating anti-tumor immune responses than either component individually. These data demonstrate a novel method for immunopotentiating VLP to increase their efficacy in the generation of anti-tumor responses via the innate ligand recognition properties of calicivirus-derived nanoparticles.
AuthorsSara J McKee, Vivienne L Young, Fiona Clow, Colin M Hayman, Margaret A Baird, Ian F Hermans, Sarah L Young, Vernon K Ward
JournalJournal of controlled release : official journal of the Controlled Release Society (J Control Release) Vol. 159 Issue 3 Pg. 338-45 (May 10 2012) ISSN: 1873-4995 [Electronic] Netherlands
PMID22386518 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2012 Elsevier B.V. All rights reserved.
Chemical References
  • Adjuvants, Immunologic
  • Cancer Vaccines
  • Galactosylceramides
  • alpha-galactosylceramide
Topics
  • Adjuvants, Immunologic (administration & dosage, therapeutic use)
  • Animals
  • Cancer Vaccines (administration & dosage, immunology, therapeutic use)
  • Cell Line, Tumor
  • Dendritic Cells (immunology)
  • Galactosylceramides (administration & dosage, immunology, therapeutic use)
  • Hemorrhagic Disease Virus, Rabbit (genetics, immunology)
  • Male
  • Melanoma, Experimental (immunology, therapy)
  • Mice
  • Mice, Inbred C57BL
  • Neoplasm Transplantation
  • T-Lymphocytes (immunology)
  • Virion (genetics, immunology)

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