Induction of a melanoma-specific antibody response by a monovalent, but not a divalent, synthetic GM2 neoglycopeptide.
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.
Bay
S
S
Institut Pasteur, Unité de Chimie des Biomolécules, URA CNRS, Paris, France. sylvie.bay@pasteur.fr
Fort
S
S
Birikaki
L
L
Ganneau
C
C
Samain
E
E
Coïc
Y-M
YM
Bonhomme
F
F
Dériaud
E
E
Leclerc
C
C
Lo-Man
R
R
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
D000906:Antibodies; D005678:G(M2) Ganglioside