title: Short synthetic glycopeptides successfully induce antibody responses to carcinoma-associated Tn antigen.
abstract: Glycopeptides containing a tumor-associated carbohydrate antigen (mono-, tri- or hexa-Tn antigen) as a B-cell epitope and a CD4+ T-cell epitope (PV: poliovirus or TT: tetanus toxin) were prepared for immunological studies. Several Tn antigen residues [FmocSer/Thr (alpha-GalNAc)-OH] were successively incorporated into the peptide sequence with unprotected carbohydrate groups. The tri- and hexa-Tn glycopeptides were recognized by MLS128, a Tn-specific monoclonal antibody. The position of the tri-Tn motif in the peptide sequence and the peptide backbone itself do not alter its antigenicity. As demonstrated by both ELISA and FACS analysis, the glycopeptides induced high titers of anti-Tn antibodies in mice, in the absence of a carrier molecule. In addition, the generated antibodies recognized the native Tn antigen on cancer cells. The antibody response obtained with a D-(Tn3)-PV glycopeptide containing three alpha-GalNAc-D-serine residues is similar that obtained with the Tn6-PV glycopeptide. These results demonstrate that short synthetic glycopeptides are able to induce anticancer antibody responses.
authors.affiliation: Unité de Chimie Organique, Institut Pasteur, Paris, France.
authors.forename: S
authors.initials: S
authors.lastname: Vichier-Guerre
authors.forename: R
authors.initials: R
authors.lastname: Lo-Man
authors.forename: S
authors.initials: S
authors.lastname: Bay
authors.forename: E
authors.initials: E
authors.lastname: Deriaud
authors.forename: H
authors.initials: H
authors.lastname: Nakada
authors.forename: C
authors.initials: C
authors.lastname: Leclerc
authors.forename: D
authors.initials: D
authors.lastname: Cantacuzène
mesh_terms: D000818:Animals; D000912:Antibodies, Neoplasm / Q000097:blood; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology*; D002277:Carcinoma / Q000276:immunology*; D005260:Female; D006020:Glycopeptides / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C
chemical_list: D000912:Antibodies, Neoplasm; D015295:Antigens, Tumor-Associated, Carbohydrate; D019496:Cancer Vaccines; D006020:Glycopeptides; C040286:Tn antigen