Synthetic and immunological studies of 5'-N-phenylacetyl sTn to develop carbohydrate-based cancer vaccines and to explore the impacts of linkage between carbohydrate antigens and carrier proteins.
Synthetic and immunological studies of 5'-N-phenylacetyl sTn to develop carbohydrate-based cancer vaccines and to explore the impacts of linkage between carbohydrate antigens and carrier proteins.
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DOI：
10.1021/bc800243f
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发表时间：
2008-10
影响因子：
4.7
通讯作者：
Guo, Zhongwu
中科院分区：
文献类型：
--
作者：
Wang, Qianli;Ekanayaka, Sandamali Amarasingha;Wu, Jian;Zhang, Junping;Guo, Zhongwu
5′-N-苯乙酰sTn（sTnNPhAc）是一种由多种肿瘤表达的sTn抗原的非天然衍生物，制备了sTn的α-连接蛋白偶联物，并对其进行了研究，以探索糖偶联物肿瘤疫苗。sTnNPhAcα-KLH引起了强有力的T细胞依赖性免疫。来自sTnNPhAc α或sTnNPhAcβ-KLH接种小鼠的抗血清对sTnNPhAcα和sTnNPhAcβ具有相似的反应性，但对sTn、NeuNPhAcα GalNAc（sTnNPhAc的区域异构体）、分离的苯乙酰基以及用于缀合sTnNPhAc和载体蛋白的接头显示非常小的反应性。结论是sTnNPhAc诱导的免疫是针对整个抗原而不是sTnNPhAc的苯乙酰基或其他部分结构的，并且sTnNPhAc的还原末端构型或连接不影响其免疫特性。还得出结论，设计用于缀合碳水化合物和蛋白质的新接头不会引起任何免疫反应，并且该接头以及相关的新且方便的偶联策略可以安全地用于糖缀合物疫苗的开发。
5′-N-Phenylacetyl sTn (sTnNPhAc), an unnatural derivative of sTn antigen expressed by many tumors, and its α-linked protein conjugates were prepared and investigated to explore glycoconjugate cancer vaccines. sTnNPhAcα-KLH elicited a robust T cell-dependent immunity. The antiserum derived from sTnNPhAcα- or sTnNPhAcβ-KLH-inoculated mice was similarly reactive to sTnNPhAcα and sTnNPhAcβ but showed very little reactivity to sTn, NeuNPhAcα GalNAc – a regioisomer of sTnNPhAc, isolated phenylacetyl group, and the linker employed to conjugate sTnNPhAc and carrier protein. It was concluded that the sTnNPhAc-elicited immunity was specific for the whole antigen rather than the phenylacetyl group or other partial structures of sTnNPhAc and that the reducing end configuration or linkage of sTnNPhAc did not affect its immunological identity. It was also concluded that a new linker designed to conjugate carbohydrates and proteins did not provoke any immune reaction and that the linker, as well as the associated new and convenient coupling strategy, can be safely used for the development of glycoconjugate vaccines.
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