title: First self-adjuvant multicomponent potential vaccine candidates by tethering of four or eight MUC1 antigenic immunodominant PDTRP units on a calixarene platform: synthesis and biological evaluation.
abstract: MUC1 protein overexpressed in human epithelial carcinoma is a target in development of novel anticancer vaccines. Multiple units of immunodominant B-cell epitope PDTRP MUC1 core sequence were conjugated to calix[4,8]arene platforms containing TLR2 ligand, to produce two novel anticancer self-adjuvant vaccine candidates. The immunogenicity of the synthetic constructs was investigated by immunization of mice in vivo. ELISA assay evidenced that the vaccine candidates stimulate anti MUC1 IgG antibody production (major for the octavalent construct) and no additive effect but a multivalency effect was observed when compared to an analogous monovalent. Octa- and tetravalent constructs lacking in PDTRP peptide moieties did not show anti MUC1 IgG antibody production in mice. The antibodies induced by the synthesized constructs are able to recognize the MUC1 structures present on MCF7 tumor cells. The results display that calixarenes are convenient platforms for building multicomponent self-adjuvant vaccine constructs promising as immunotherapeutic anticancer agents.
authors.affiliation: CNR Istituto di Chimica Biomolecolare, Via P. Gaifami 18, I-95126 Catania, Italy.
authors.forename: Corrada
authors.initials: C
authors.lastname: Geraci
authors.forename: Grazia M L
authors.initials: GM
authors.lastname: Consoli
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Granata
authors.forename: Eva
authors.initials: E
authors.lastname: Galante
authors.forename: Angelo
authors.initials: A
authors.lastname: Palmigiano
authors.forename: Maria
authors.initials: M
authors.lastname: Pappalardo
authors.forename: Salvatore D
authors.initials: SD
authors.lastname: Di Puma
authors.forename: Angelo
authors.initials: A
authors.lastname: Spadaro
mesh_terms: D000276:Adjuvants, Immunologic / Q000737:chemistry* / Q000627:therapeutic use; D000818:Animals; D000917:Antibody Formation; D047250:Calixarenes / Q000737:chemistry* / Q000627:therapeutic use; D019496:Cancer Vaccines / Q000737:chemistry* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D016056:Immunodominant Epitopes / Q000737:chemistry* / Q000627:therapeutic use; D007074:Immunoglobulin G / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018396:Mucin-1 / Q000737:chemistry* / Q000276:immunology / Q000627:therapeutic use; D009369:Neoplasms / Q000276:immunology / Q000517:prevention & control*; D009842:Oligopeptides / Q000737:chemistry / Q000627:therapeutic use; D051195:Toll-Like Receptor 2 / Q000737:chemistry
chemical_list: D000276:Adjuvants, Immunologic; D019496:Cancer Vaccines; D016056:Immunodominant Epitopes; D007074:Immunoglobulin G; D018396:Mucin-1; D009842:Oligopeptides; D051195:Toll-Like Receptor 2; D047250:Calixarenes