title: Efficient Eradication of Established Tumors in Mice with Cationic Liposome-Based Synthetic Long-Peptide Vaccines.
abstract: Therapeutic vaccination with synthetic long peptides (SLP) can be clinically effective against HPV-induced premalignant lesions; however, their efficiency in established malignant lesions leaves room for improvement. Here, we report the high therapeutic potency of cationic liposomes loaded with well-defined tumor-specific SLPs and a TLR3 ligand as adjuvant. The cationic particles, with an average size of 160 nm, could strongly activate functional, antigen-specific CD8+and CD4+T cells and inducedin vivocytotoxicity against target cells after intradermal vaccination. At a low dose (1 nmol) of SLP, our liposomal formulations significantly controlled tumor outgrowth in two independent models (melanoma and HPV-induced tumors) and even cured 75%-100% of mice of their large established tumors. Cured mice were fully protected from a second challenge with an otherwise lethal dose of tumor cells, indicating the potential of liposomal SLP in the formulation of powerful vaccines for cancer immunotherapy.Cancer Immunol Res; 5(3); 222-33. ©2017 AACR.
authors.affiliation: Division of Drug Delivery Technology, Cluster BioTherapeutics, 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, Cluster BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden, the Netherlands.
authors.forename: Naomi
authors.initials: N
authors.lastname: Benne
authors.affiliation: Division of Drug Delivery Technology, Cluster BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden, the Netherlands.
authors.forename: Joke
authors.initials: J
authors.lastname: Bouwstra
authors.affiliation: Division of Drug Delivery Technology, Cluster BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden, the Netherlands. f.a.ossendorp@lumc.nl w.jiskoot@lacdr.leidenuniv.nl.
authors.forename: Wim
authors.initials: W
authors.lastname: Jiskoot
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Centre, Leiden, the Netherlands. f.a.ossendorp@lumc.nl w.jiskoot@lacdr.leidenuniv.nl.
authors.forename: Ferry
authors.initials: F
authors.lastname: Ossendorp
mesh_terms: D000276:Adjuvants, Immunologic; D000595:Amino Acid Sequence; D000818:Animals; D000951:Antigens, Neoplasm / Q000737:chemistry / Q000276:immunology; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology*; D004195:Disease Models, Animal; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000276:immunology; D005260:Female; D006801:Humans; D007114:Immunization; D008081:Liposomes; D008546:Melanoma, Experimental; D051379:Mice; D009369:Neoplasms / Q000276:immunology* / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D050725:Papillomavirus E7 Proteins / Q000737:chemistry / Q000276:immunology; D011070:Poly I-C; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D018984:Epitopes, T-Lymphocyte; D008081:Liposomes; D050725:Papillomavirus E7 Proteins; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic; D011070:Poly I-C