Journal
VACCINE
Volume 33, Issue 43, Pages 5838-5844Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.vaccine.2015.08.083
Keywords
Cancer vaccines; Melanoma; Liposomes; Long peptides; Invariant natural killer T cells; alpha-Galactosylceramide
Categories
Funding
- New Zealand Ministry of Science and Innovation [C08X0808]
- New Zealand Ministry of Business, Innovation & Employment (MBIE) [C08X0808] Funding Source: New Zealand Ministry of Business, Innovation & Employment (MBIE)
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The lipid antigen a-galactosylceramide (alpha-GalCer) is a potent activator of invariant natural killer T-cells (iNKT cells) and can stimulate cytotoxic and anti-tumour immune responses. However optimal responses appear to be induced by alpha-GalCer when cell-based vaccines are delivered intravenously. Here we investigated if co-delivery of protein and peptide antigens along with alpha-GalCer in a liposomal formulation could stimulate therapeutic anti-tumour immune responses. Cationic liposomes were inherently immune-stimulatory and induced cytotoxic immune responses when delivered both by intravenous and subcutaneous injection. However, only vaccine delivered intravenously stimulated therapeutic antitumour immune responses to a peptide antigen. Surface modification with polyethylene glycol (PEG) did not improve immune responses to either intravenously or subcutaneously delivered vaccines. Immune responses to short and long peptide sequences (CD8 and CD4 epitopes) of the self-antigen tyrosinase-related protein 2 (TRP2) as a vaccine antigen, co-delivered with alpha-GalCer in either cationic liposomes or PBS were further examined. Enhanced production of IFN-gamma, increased cytotoxic T-cell responses and tumour survival were observed when a long TRP2-peptide was delivered with alpha-GalCer in cationic liposomes. (C) 2015 Elsevier Ltd. All rights reserved.
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