The Quest for Anticancer Vaccines: Deciphering the Fine-Epitope Specificity of Cancer-Related Monoclonal Antibodies by Combining Microarray Screening and Saturation Transfer Difference NMR
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- 作者：Helena Coelho ; Takahiko Matsushita ; Gerard Artigas ; Hiroshi Hinou ; F. Javier Ca帽ada ; Richard Lo-Man ; Claude Leclerc ; Eurico J. Cabrita ; Jes煤s Jim茅nez-Barbero ; Shin-Ichiro Nishimura ; Fayna Garcia-Mart铆n ; Filipa Marcelo
- 刊名：Journal of the American Chemical Society
- 出版年：2015
- 出版时间：October 7, 2015
- 年：2015
- 卷：137
- 期：39
- 页码：12438-12441
- 全文大小：342K
- ISSN：1520-5126
文摘
The identification of MUC1 tumor-associated Tn antigen (伪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鈥揳ntibody recognition, with particular relevance for the development of Tn-MUC1-based anticancer vaccines.