Induction of a Melanoma‐Specific Antibody Response by a Monovalent, but not a Divalent, Synthetic GM2 Neoglycopeptide

• Published in: ChemMedChem 2009-04, Vol.4 (4), p.582-587
• Main Authors: Bay, S., Fort, S., Birikaki, L., Ganneau, C., Samain, E., Coïc, Y‐M., Bonhomme, F., Dériaud, E., Leclerc, C., Lo‐Man, R.
• Format: Article
• Language: English
• Subjects: Animals; Antibodies - immunology; Antibody Specificity - immunology; antitumor agents; Carbohydrate Sequence; carbohydrates; G(M2) Ganglioside - chemical synthesis; G(M2) Ganglioside - chemistry; G(M2) Ganglioside - immunology; glycopeptides; Humans; immunology; Jurkat Cells; Melanoma - immunology; Mice; Mice, Inbred BALB C; Molecular Sequence Data; synthetic vaccines
• ISSN: 1860-7179; 1860-7187
• DOI: 10.1002/cmdc.200900032

Human tumor cell‐specific antibodies were induced in mice after immunization with a synthetic glycopeptide, which is based on the GM2 ganglioside carbohydrate moiety produced on a gram scale in bacteria. Such neoglycopeptides represent a promising cancer vaccine strategy for active immunotherapy targeting carbohydrates. 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. Human tumor cell‐specific antibodies were induced in mice after immunization with a synthetic glycopeptide, which is based on the GM2 ganglioside carbohydrate moiety produced on a gram scale in bacteria. Such neoglycopeptides represent a promising cancer vaccine strategy for active immunotherapy targeting carbohydrates.