title: Synthetic long peptide-based vaccine formulations for induction of cell mediated immunity: A comparative study of cationic liposomes and PLGA nanoparticles.
abstract: Nanoparticulate formulations for synthetic long peptide (SLP)-cancer vaccines as alternative to clinically used Montanide ISA 51- and squalene-based emulsions are investigated in this study. SLPs were loaded into TLR ligand-adjuvanted cationic liposomes and PLGA nanoparticles (NPs) to potentially induce cell-mediated immune responses. The liposomal and PLGA NP formulations were successfully loaded with up to four different compounds and were able to enhance antigen uptake by dendritic cells (DCs) and subsequent activation of T cells in vitro. Subcutaneous vaccination of mice with the different formulations showed that the SLP-loaded cationic liposomes were the most efficient for the induction of functional antigen-T cells in vivo, followed by PLGA NPs which were as potent as or even more than the Montanide and squalene emulsions. Moreover, after transfer of antigen-specific target cells in immunized mice, liposomes induced the highest in vivo killing capacity. These findings, considering also the inadequate safety profile of the currently clinically used adjuvant Montanide ISA-51, make these two particulate, biodegradable delivery systems promising candidates as delivery platforms for SLP-based immunotherapy of cancer.
authors.affiliation: Division of Drug Delivery Technology, Leiden Academic Centre for Drug Research, Leiden, The Netherlands.
authors.forename: Eleni Maria
authors.initials: EM
authors.lastname: Varypataki
authors.affiliation: Division of Drug Delivery Technology, Leiden Academic Centre for Drug Research, Leiden, The Netherlands.
authors.forename: Ana Luisa
authors.initials: AL
authors.lastname: Silva
authors.affiliation: Vaccine Formulation Laboratory, Department of Biochemistry, University of Lausanne, Switzerland.
authors.forename: Christophe
authors.initials: C
authors.lastname: Barnier-Quer
authors.affiliation: Vaccine Formulation Laboratory, Department of Biochemistry, University of Lausanne, Switzerland.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Collin
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Centre, Leiden, The Netherlands.
authors.forename: Ferry
authors.initials: F
authors.lastname: Ossendorp
authors.affiliation: Division of Drug Delivery Technology, Leiden Academic Centre for Drug Research, Leiden, The Netherlands. Electronic address: w.jiskoot@lacdr.leidenuniv.nl.
authors.forename: Wim
authors.initials: W
authors.lastname: Jiskoot
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology; D002412:Cations / Q000737:chemistry; D005260:Female; D007111:Immunity, Cellular; D007114:Immunization; D019344:Lactic Acid / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry*; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000737:chemistry*; D009369:Neoplasms / Q000276:immunology / Q000628:therapy; D010047:Ovalbumin / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology; D010455:Peptides / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D014614:Vaccines, Synthetic / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology
chemical_list: D019496:Cancer Vaccines; D002412:Cations; D008081:Liposomes; D010455:Peptides; D014614:Vaccines, Synthetic; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D010047:Ovalbumin
keywords: Cationic liposomes; Cellular immune response; PLGA nanoparticles; Synthetic long peptides; TLR ligands