Abstract
PurposePersonalized peptide-based cancer vaccines will be composed of multiple patient specific synthetic long peptides (SLPs) which may have various physicochemical properties. To formulate such SLPs, a flexible vaccine delivery system is required. We studied whether cationic liposomes are suitable for this purpose.MethodsFifteen SIINFEKL T cell epitope-containing SLPs, widely differing in hydrophobicity and isoelectric point, were separately loaded in cationic liposomes via the dehydration-rehydration method. Particle size and polydispersity index (PDI) were measured via dynamic light scattering (DLS), and zeta potential with laser Doppler electrophoresis. Peptide loading was fluorescently determined and the immunogenicity of the formulated peptides was assessed in co-cultures of dendritic cells (DCs) and CD8+ T-cells in vitro.ResultsAll SLPs were loaded in cationic liposomes by using three different loading method variants, depending on the SLP characteristics. The fifteen liposomal formulations had a comparable size (< 200 nm), PDI (< 0.3) and zeta potential (22–30 mV). Cationic liposomes efficiently delivered the SLPs to DCs that subsequently activated SIINFEKL-specific CD8+ T-cells, indicating improved immunological activity of the SLPs.ConclusionCationic liposomes can accommodate a wide range of different SLPs and are therefore a potential delivery platform for personalized cancer vaccines.
Highlights
Therapeutic cancer vaccines aim to amplify a specific cellular immune response directed towards the patients’ own tumor [1,2]
All synthetic long peptides (SLPs) were loaded in cationic liposomes by using three different loading method variants, depending on the SLP characteristics
Cationic liposomes efficiently delivered the SLPs to dendritic cells (DCs) that subsequently activated SIINFEKL-specific CD8+ T-cells, indicating improved immunological activity of the SLPs
Summary
Therapeutic cancer vaccines aim to amplify a specific cellular immune response directed towards the patients’ own tumor [1,2]. T-cells are able to identify and destroy malignant cells through the recognition of tumor specific antigens. Vaccination with synthetic long peptides (SLPs) containing a cytotoxic (CD8+) as well as a helper (CD4+) T cell epitope has shown to induce tumor specific T cell responses that were able to control or even regress tumor outgrowth [1,2,3,4,5,6,7]. In order to provoke such functional immune responses, the SLPs have to be delivered to and taken up by dendritic cells (DCs), and be processed and presented on MHC molecules to activate 207 Page 2 of 9. SLPs by themselves are poorly immunogenic due to inefficient uptake by DCs, resulting in low levels of antigen presentation and subsequent T cell activation [1,4,7,8]. A proper formulation of the SLPs with adjuvants and a delivery vehicle is essential to compose an adequate immunogenic SLP vaccine [1,4,5,7,8]
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