Short synthetic glycopeptides successfully induce antibody responses to carcinoma-associated Tn antigen.
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.
Vichier-Guerre
S
S
Unité de Chimie Organique, Institut Pasteur, Paris, France.
Lo-Man
R
R
Bay
S
S
Deriaud
E
E
Nakada
H
H
Leclerc
C
C
Cantacuzène
D
D
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
D000912:Antibodies, Neoplasm; D015295:Antigens, Tumor-Associated, Carbohydrate; D019496:Cancer Vaccines; D006020:Glycopeptides; C040286:Tn antigen