title: Systematic amino acid substitutions improved efficiency of GD2-peptide mimotope vaccination against neuroblastoma.
abstract: The likelihood of identifying peptides of sufficient quality for the development of effective cancer vaccines by screening of phage display libraries is low. Here, we introduce the sequential application of systematic amino acid substitution by SPOT synthesis. After the substitution of two amino acids within the sequence of a phage display-derived mimotope of disialoganglioside GD2 (mimotope MA), the novel mimotope C3 showed improved GD2 mimicry in vitro. Peptide vaccination with the C3 mimotope induced an 18-fold increased anti-GD2 serum response associated with reduction of primary tumour growth and spontaneous metastasis in contrast to MA mimotope controls in a syngeneic neuroblastoma model. In summary, SPOT provides an ideal optimisation tool for the development of phage display-derived cancer vaccines.
authors.affiliation: Charité - Universitätsmedizin Berlin, Department of Pediatrics, Experimental Oncology, Berlin, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Bleeke
authors.forename: Stefan
authors.initials: S
authors.lastname: Fest
authors.forename: Nicole
authors.initials: N
authors.lastname: Huebener
authors.forename: Christiane
authors.initials: C
authors.lastname: Landgraf
authors.forename: Burkhart
authors.initials: B
authors.lastname: Schraven
authors.forename: Gerhard
authors.initials: G
authors.lastname: Gaedicke
authors.forename: Rudolf
authors.initials: R
authors.lastname: Volkmer
authors.forename: Holger N
authors.initials: HN
authors.lastname: Lode
mesh_terms: D019943:Amino Acid Substitution / Q000235:genetics*; D000818:Animals; D019496:Cancer Vaccines / Q000235:genetics* / Q000276:immunology; D045744:Cell Line, Tumor; D005260:Female; D005732:Gangliosides / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007110:Immunity, Active / Q000235:genetics / Q000276:immunology; D007074:Immunoglobulin G / Q000378:metabolism; D051379:Mice; D018716:Molecular Mimicry / Q000235:genetics*; D009368:Neoplasm Transplantation; D009447:Neuroblastoma / Q000473:pathology / Q000517:prevention & control*; D040081:Protein Array Analysis / Q000379:methods
chemical_list: D019496:Cancer Vaccines; D005732:Gangliosides; D007074:Immunoglobulin G; C025447:sialogangliosides