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 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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DOI：
10.1021/jacs.5b06787
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发表时间：
2015-10-07
影响因子：
15
通讯作者：
Marcelo, Filipa
中科院分区：
文献类型：
--
作者：
Coelho, Helena;Matsushita, Talcahiko;Marcelo, Filipa
MUC1肿瘤相关Tn抗原（alpha GalpNAc1-O-Ser/Thr）的鉴定促进了抗癌疫苗的开发。结合微阵列和饱和转移差异核磁共振，我们已经表征了MUC1化学文库（裸和n-糖基化）对两个癌症相关单克隆抗体家族（抗MUC1和抗tn单克隆抗体）的精细表位定位。抗muc1单抗克隆VU-3C6和VU-11E2识别muc1衍生的裸肽，并以肽序列依赖的方式结合GalNAc。相比之下，抗tn单抗克隆8D4和14D6主要识别GalNAc，不结合裸muc1衍生肽。这些抗tn单克隆抗体显示出对含有n-丝氨酸抗原的糖肽的明显偏好，而不是n-苏氨酸类似物，强调了潜在氨基酸（丝氨酸或苏氨酸）在结合过程中的作用。一般来说，报道的策略可以用来揭示调节抗原抗体识别的关键最小结构特征，特别是与基于n- muc1的抗癌疫苗的开发相关。
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.