title: Optimal organization of a polypeptide-based candidate cancer vaccine composed of cryptic tumor peptides with enhanced immunogenicity.
abstract: Polyspecific tumor vaccination should offer broad control of tumor cells and reduce the risk of emergence of immune escape variants. Here, we evaluated the capacity of a polypeptide composed of optimized cryptic peptides derived from three different universal tumor antigens (TERT988Y, HER-2/neu402Y and MAGE-A248V9) to induce a polyspecific CD8 cell response both in vivo in HHD mice and in vitro in humans. A mixture of TERT988Y, HER-2/neu402Y and MAGE-A248V9 peptides failed to induce a trispecific response. In contrast, a polypeptide composed of the three peptides stimulated a trispecific immune response. Interestingly, the capacity of the polypeptide to induce a trispecific response depended on its internal organization. Six different polypeptide variants corresponding to all possible combinations of the three peptides were tested. Only one variant, named Poly-6, elicited an immune response simultaneously targeting all three peptides.
authors.affiliation: Vaxon Biotech, Génopole bat G2, 2 rue Gaston Crémieux, 91057 Evry, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Cornet
authors.forename: Isabelle
authors.initials: I
authors.lastname: Miconnet
authors.forename: Jeanne
authors.initials: J
authors.lastname: Menez
authors.forename: François
authors.initials: F
authors.lastname: Lemonnier
authors.forename: Kostas
authors.initials: K
authors.lastname: Kosmatopoulos
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology*; D002460:Cell Line; D051379:Mice; D009363:Neoplasm Proteins / Q000008:administration & dosage / Q000096:biosynthesis / Q000276:immunology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000138:chemical synthesis / Q000276:immunology*; D017778:Vaccines, Combined / Q000008:administration & dosage / Q000276:immunology; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology
chemical_list: D019496:Cancer Vaccines; D009363:Neoplasm Proteins; D010446:Peptide Fragments; D017778:Vaccines, Combined; D022223:Vaccines, Subunit