Synthetic TRP2 long-peptide and α-galactosylceramide formulated into cationic liposomes elicit CD8+ T-cell responses and prevent tumour progression. Issue 43 (26th October 2015)

• Record Type: Journal Article
• Authors: Neumann, Silke; Young, Katie; Compton, Benji; Anderson, Regan; Painter, Gavin; Hook, Sarah
• Is Part Of: Vaccine. Volume 33:Issue 43(2015)
• Page Start: 5838
• Page End: 5844
• Publication Date: 2015-10-26
• Subjects: Cancer vaccines -- Melanoma -- Liposomes -- Long peptides -- Invariant natural killer T cells -- α-Galactosylceramide; Vaccines -- Periodicals; 615.372
• DOI: 10.1016/j.vaccine.2015.08.083
• Languages: English
• ISSNs: 0264-410X

Abstract

Highlights: SC immunisation with liposomal α-GalCer vaccine induced cytotoxic T-cell responses. Delayed tumour growth after IV but not SC administration of liposomal vaccine. Optimal responses to peptide antigens require co-delivery with α-GalCer. Abstract: The lipid antigen α-galactosylceramide (α-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 α-GalCer when cell-based vaccines are delivered intravenously. Here we investigated if co-delivery of protein and peptide antigens along with α-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 anti-tumour 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 α-GalCer in either cationic liposomes or PBS were further examined. Enhanced production of IFN-γ, increased cytotoxic T-cell responses and tumour survival were observed when a long TRP2-peptide was delivered with α-GalCer in cationic liposomes.