4.5 Article

Cationic Liposomes: A Flexible Vaccine Delivery System for Physicochemically Diverse Antigenic Peptides

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PHARMACEUTICAL RESEARCH
卷 35, 期 11, 页码 -

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SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s11095-018-2490-6

关键词

cationic liposomes; immunogenicity; neoepitope; synthetic long peptides; therapeutic cancer vaccine

资金

  1. Molecule to Patient program of the Translational Drug Discovery and Development (TDDD) profiling area of University Leiden, The Netherlands

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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 (< 200nm), PDI (< 0.3) and zeta potential (22-30mV). 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.

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