TY - JOUR
T1 - The Quest for Anticancer Vaccines: Deciphering the Fine-Epitope Specificity of Cancer-Related Monoclonal Antibodies by Combining Microarray Screening and Saturation Transfer Difference NMR
AU - Coelho, Helena
AU - Matsushita, Talcahiko
AU - Artigas, Gerard
AU - Hinou, Hiroshi
AU - Javier Canada, F.
AU - Lo-Man, Richard
AU - Leclerc, Claude
AU - Cabrita, Eurico J.
AU - Jimenez-Barbero, Jesus
AU - Nishimura, Shin-Ichiro
AU - Garcia-Martin, Fayna
AU - Marcelo, Filipa Margarida Barradas Morais
N1 - Sem PDF.
PY - 2015/10/7
Y1 - 2015/10/7
N2 - The identification of MUC1 tumor-associated Tn antigen (alpha GalpNAc1-O-Ser/Thr) has boosted the development of anticancer vaccines. Combining microarrays and saturation transfer difference NMR, we have characterized the fine-epitope mapping of a MUC1 chemical library (naked and Tn-glycosylated) toward two families of cancer-related monoclonal antibodies (anti-MUC1 and anti-Tn mAbs). Anti-MUC1 mAbs clone VU-3C6 and VU-11E2 recognize naked MUC1-derived peptides and bind GalNAc in a peptide-sequence-dependent manner. In contrast, anti-Tn mAbs clone 8D4 and 14D6 mostly recognize the GalNAc and do not bind naked MUC1-derived peptides. These anti-Tn mAbs show a clear preference for glycopeptides containing the Tn-Ser antigen rather than the Tn-Thr analogue, stressing the role of the underlying amino acid (serine or threonine) in the binding process. The reported strategy can be employed, in general, to unveil the key minimal structural features that modulate antigen-antibody recognition, with particular relevance for the development of Tn-MUC1-based anticancer vaccines.
AB - The identification of MUC1 tumor-associated Tn antigen (alpha GalpNAc1-O-Ser/Thr) has boosted the development of anticancer vaccines. Combining microarrays and saturation transfer difference NMR, we have characterized the fine-epitope mapping of a MUC1 chemical library (naked and Tn-glycosylated) toward two families of cancer-related monoclonal antibodies (anti-MUC1 and anti-Tn mAbs). Anti-MUC1 mAbs clone VU-3C6 and VU-11E2 recognize naked MUC1-derived peptides and bind GalNAc in a peptide-sequence-dependent manner. In contrast, anti-Tn mAbs clone 8D4 and 14D6 mostly recognize the GalNAc and do not bind naked MUC1-derived peptides. These anti-Tn mAbs show a clear preference for glycopeptides containing the Tn-Ser antigen rather than the Tn-Thr analogue, stressing the role of the underlying amino acid (serine or threonine) in the binding process. The reported strategy can be employed, in general, to unveil the key minimal structural features that modulate antigen-antibody recognition, with particular relevance for the development of Tn-MUC1-based anticancer vaccines.
KW - MOLECULAR RECOGNITION
KW - STRUCTURAL ELEMENTS
KW - LIGAND-BINDING
KW - CELL-SURFACE
KW - TN-ANTIGEN
KW - MUC1
KW - GLYCOSYLATION
KW - GLYCOPEPTIDES
KW - PEPTIDES
KW - GLYCOPROTEIN
U2 - 10.1021/jacs.5b06787
DO - 10.1021/jacs.5b06787
M3 - Article
C2 - 26366611
SN - 0002-7863
VL - 137
SP - 12438
EP - 12441
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
IS - 39
ER -
