title: Memory and effector CD8 T-cell responses after nanoparticle vaccination of melanoma patients.
abstract: Induction of cytotoxic CD8 T-cell responses is enhanced by the exclusive presentation of antigen through dendritic cells, and by innate stimuli, such as toll-like receptor ligands. On the basis of these 2 principles, we designed a vaccine against melanoma. Specifically, we linked the melanoma-specific Melan-A/Mart-1 peptide to virus-like nanoparticles loaded with A-type CpG, a ligand for toll-like receptor 9. Melan-A/Mart-1 peptide was cross-presented, as shown in vitro with human dendritic cells and in HLA-A2 transgenic mice. A phase I/II study in stage II-IV melanoma patients showed that the vaccine was well tolerated, and that 14/22 patients generated ex vivo detectable T-cell responses, with in part multifunctional T cells capable to degranulate and produce IFN-γ, TNF-α, and IL-2. No significant influence of the route of immunization (subcutaneous versus intradermal) nor dosing regimen (weekly versus daily clusters) could be observed. It is interesting to note that, relatively large fractions of responding specific T cells exhibited a central memory phenotype, more than what is achieved by other nonlive vaccines. We conclude that vaccination with CpG loaded virus-like nanoparticles is associated with a human CD8 T-cell response with properties of a potential long-term immune protection from the disease.
authors.affiliation: Clinical Tumor Immune-Biology Unit, Ludwig Institute for Cancer Research, Lausanne branch, Switzerland. daniel.speiser@hospvd.ch
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Speiser
authors.forename: Katrin
authors.initials: K
authors.lastname: Schwarz
authors.forename: Petra
authors.initials: P
authors.lastname: Baumgaertner
authors.forename: Vania
authors.initials: V
authors.lastname: Manolova
authors.forename: Estelle
authors.initials: E
authors.lastname: Devevre
authors.forename: Wolfram
authors.initials: W
authors.lastname: Sterry
authors.forename: Peter
authors.initials: P
authors.lastname: Walden
authors.forename: Alfred
authors.initials: A
authors.lastname: Zippelius
authors.forename: Katrin Baumann
authors.initials: KB
authors.lastname: Conzett
authors.forename: Gabriela
authors.initials: G
authors.lastname: Senti
authors.forename: Verena
authors.initials: V
authors.lastname: Voelter
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Cerottini
authors.forename: David
authors.initials: D
authors.lastname: Guggisberg
authors.forename: Jörg
authors.initials: J
authors.lastname: Willers
authors.forename: Christine
authors.initials: C
authors.lastname: Geldhof
authors.forename: Pedro
authors.initials: P
authors.lastname: Romero
authors.forename: Thomas
authors.initials: T
authors.lastname: Kündig
authors.forename: Alexander
authors.initials: A
authors.lastname: Knuth
authors.forename: Reinhard
authors.initials: R
authors.lastname: Dummer
authors.forename: Uwe
authors.initials: U
authors.lastname: Trefzer
authors.forename: Martin F
authors.initials: MF
authors.lastname: Bachmann
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D019496:Cancer Vaccines; D002454:Cell Differentiation; D002478:Cells, Cultured; D005260:Female; D015789:HLA-A2 Antigen / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007156:Immunologic Memory; D008213:Lymphocyte Activation; D058965:MART-1 Antigen / Q000737:chemistry / Q000276:immunology; D008297:Male; D008545:Melanoma / Q000276:immunology / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D051379:Mice; D008822:Mice, Transgenic; D008875:Middle Aged; D053758:Nanoparticles / Q000737:chemistry; D009838:Oligodeoxyribonucleotides / Q000737:chemistry / Q000276:immunology; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D012878:Skin Neoplasms / Q000276:immunology / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D016896:Treatment Outcome; D058425:Vaccines, Virus-Like Particle
chemical_list: C408982:CPG-oligonucleotide; D019496:Cancer Vaccines; D015789:HLA-A2 Antigen; D058965:MART-1 Antigen; D009838:Oligodeoxyribonucleotides; D010446:Peptide Fragments; D058425:Vaccines, Virus-Like Particle