1 research outputs found
The Quest for Anticancer Vaccines: Deciphering the Fine-Epitope Specificity of Cancer-Related Monoclonal Antibodies by Combining Microarray Screening and Saturation Transfer Difference NMR
The identification of MUC1 tumor-associated
Tn antigen (αGalpNAc1-<i>O</i>-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