【摘 要】
：
The over-expression of saccharides such as Globo-H,LewisY and Tn antigen is a common feature of oncogenic transformed cells.Endeavors to exploit this aberrant glycosylation for cancer vaccine developm
【机 构】
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Complex Carbohydrate Research Center University Of Georgia USA
【出 处】
：
2008中国深圳蛋白质和多肽科学大会
论文部分内容阅读
The over-expression of saccharides such as Globo-H,LewisY and Tn antigen is a common feature of oncogenic transformed cells.Endeavors to exploit this aberrant glycosylation for cancer vaccine development has been complicated by difficulties of eliciting high titers of IgG antibodies against classical conjugates of tumor-associated carbohydrates to carrier proteins.We have designed,chemical synthesized and immunologically evaluated a number of fully synthetic vaccine candidates to establish strategies to overcome the poor immunogenicity of tumor-associated carbohydrates and glycopeptides.We have found that a three-component vaccine composed of a TLR2 agonist,a promiscuous peptide T-helper epitope and a tumor-associated glycopeptide,can elicit in mice exceptionally high titers of IgG antibodies that can recognize cancer cells expressing the tumor-associated carbohydrate.The superior properties of the vaccine candidate are attributed to the local production of cytokines,upregulation of co-s timulatory proteins,enhanced uptake by macrophages and dendritic cells and avoidance of epitope suppression.Our results demonstrate that medicinal chemistry approaches for drug optimization can also be employed for vaccine design.
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