title: Induction of a melanoma-specific antibody response by a monovalent, but not a divalent, synthetic GM2 neoglycopeptide.
abstract: The GM2 ganglioside represents an important target for specific anticancer immunotherapy. We designed and synthesized a neoglycopeptide immunogen displaying one or two copies of the GM2 tetrasaccharidic moiety. These glycopeptides were prepared using the Huisgen cycloaddition, which enables the efficient ligation of the alkyne-functionalized biosynthesized GM2 with an azido CD4(+) T cell epitope peptide. It is worth noting that the GM2 can be produced on a gram scale in bacteria, which can be advantageous for a scale-up of the process. We show here for the first time that a fully synthetic glycopeptide, which is based on a ganglioside carbohydrate moiety, can induce human tumor cell-specific antibodies after immunization in mice. Interestingly, the monovalent, but not the divalent, form of GM2 peptide construct induced antimelanoma antibodies. Unlike traditional vaccines, this vaccine is a pure chemically-defined entity, a key quality for consistent studies and safe clinical evaluation. Therefore, such carbohydrate-peptide conjugate represents a promising cancer vaccine strategy for active immunotherapy targeting gangliosides.
authors.affiliation: Institut Pasteur, Unité de Chimie des Biomolécules, URA CNRS, Paris, France. sylvie.bay@pasteur.fr
authors.forename: S
authors.initials: S
authors.lastname: Bay
authors.forename: S
authors.initials: S
authors.lastname: Fort
authors.forename: L
authors.initials: L
authors.lastname: Birikaki
authors.forename: C
authors.initials: C
authors.lastname: Ganneau
authors.forename: E
authors.initials: E
authors.lastname: Samain
authors.forename: Y-M
authors.initials: YM
authors.lastname: Coïc
authors.forename: F
authors.initials: F
authors.lastname: Bonhomme
authors.forename: E
authors.initials: E
authors.lastname: Dériaud
authors.forename: C
authors.initials: C
authors.lastname: Leclerc
authors.forename: R
authors.initials: R
authors.lastname: Lo-Man
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology*; D000918:Antibody Specificity / Q000276:immunology*; D002240:Carbohydrate Sequence; D005678:G(M2) Ganglioside / Q000138:chemical synthesis* / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D019169:Jurkat Cells; D008545:Melanoma / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data
chemical_list: D000906:Antibodies; D005678:G(M2) Ganglioside