Synthetic and Immunological Studies of sTn Derivatives Carrying 5-N-(p-Substituted Phenylacetyl)Sialic Acid for the Development of Effective Cancer Vaccines.
Synthetic and Immunological Studies of sTn Derivatives Carrying 5-N-(p-Substituted Phenylacetyl)Sialic Acid for the Development of Effective Cancer Vaccines.
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DOI：
10.1021/ml100313d
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发表时间：
2011-05-12
影响因子：
4.2
通讯作者：
Guo, Zhongwu
中科院分区：
文献类型：
--
作者：
Wang, Qianli;Guo, Zhongwu
关键词：
为了寻找基于sTn的有效癌症疫苗，sTn是一种由多种肿瘤表达的唾液酸化肿瘤相关糖抗原（sialo-TACA），四种非天然N-酰基sTn衍生物，包括5'-N-p-甲基苯乙酰基sTn（sTnNMePhAc）、5'-N-p-甲氧基苯乙酰基sTn（sTnNMeOPhAc）、5'-N-p-乙酰基苯乙酰基sTn (sTnNAcPhAc) 和 5’-N-p-氯苯乙酰基 sTn (sTnNClPhAc) 及其蛋白缀合物是通过高度收敛的程序合成的。这些匙孔血蓝蛋白缀合物形式的 sTn 衍生物的免疫学特性在小鼠中进行了评估，并与 sTnNPhAc（之前作为候选疫苗研究的 sTn 衍生物）的免疫学特性进行了比较。结果表明，sTnNMePhAc、sTnNMeOPhAc、sTnNAcPhAc 和 sTnNClPhAc 都比 sTnNPhAc 更具免疫原性，并且它们激发了强烈的 T 细胞依赖性 IgG1 免疫反应，可用于癌症免疫治疗。结论是 sTnNClPhAc 是癌症疫苗开发的有希望的候选者，值得进一步研究。
To search for effective cancer vaccines based on sTn, a sialylated tumor-associated carbohydrate antigen (sialo-TACA) expressed by a number of tumors, four unnatural N-acyl sTn derivatives, including 5’-N-p-methylphenylacetyl sTn (sTnNMePhAc), 5’-N-p-methoxylphenylacetyl sTn (sTnNMeOPhAc), 5’-N-p-acetylphenylacetyl sTn (sTnNAcPhAc) and 5’-N-p-chlorophenylacetyl sTn (sTnNClPhAc), as well as their protein conjugates, were synthesized by a highly convergent procedure. The immunological properties of these sTn derivatives in the form of keyhole limpet hemocyanin conjugate were evaluated in mice and compared to that of sTnNPhAc, a sTn derivative previously investigated as a vaccine candidate. It was shown that sTnNMePhAc, sTnNMeOPhAc, sTnNAcPhAc and sTnNClPhAc are all much more immunogenic than sTnNPhAc and that they provoked strong T cell-dependent IgG1 immune responses useful for cancer immunotherapy. It was concluded that sTnNClPhAc is a promising candidate for cancer vaccine development and is worthy further investigation.
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影响因子：
7.3
作者：
Pan, YB;Chefalo, P;Guo, ZW
通讯作者：
Guo, ZW
影响因子：
4.7
作者：
Wang, Qianli;Ekanayaka, Sandamali Amarasingha;Wu, Jian;Zhang, Junping;Guo, Zhongwu
通讯作者：
Guo, Zhongwu
影响因子：
2.9
作者：
Chefalo, P;Pan, YB;Harding, CV
通讯作者：
Harding, CV
影响因子：
6.2
作者：
Holmberg, Leona A;Sandmaier, Brenda M
通讯作者：
Sandmaier, Brenda M
影响因子：
16.8
作者：
Casadevall, A;Pirofski, LA
通讯作者：
Pirofski, LA