Synthesis and Evaluation of Protein Conjugates of GM3 Derivatives Carrying Modified Sialic Acids as Highly Immunogenic Cancer Vaccine Candidates.
Synthesis and Evaluation of Protein Conjugates of GM3 Derivatives Carrying Modified Sialic Acids as Highly Immunogenic Cancer Vaccine Candidates.
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DOI：
10.1039/c1md00033k
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发表时间：
2011-01-01
期刊：
影响因子：
--
通讯作者：
Guo Z
中科院分区：
文献类型：
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作者：
Yu S;Wang Q;Zhang J;Wu Q;Guo Z
GM 3是一种由许多肿瘤表达的唾液酸化三糖抗原，在治疗性癌症疫苗的设计中是一个有吸引力的靶标。然而，与GM 3相关的严重问题是其免疫原性差。为了克服这一问题，开发基于GM 3的癌症疫苗，合成了四种GM 3衍生物，包括5 '-N-p-甲基苯乙酰基、5'-N-p-甲氧基苯乙酰基、5 '-N-p-乙酰基苯乙酰基和5'-N-p-氯苯乙酰基GM 3，然后将其偶联到载体蛋白钥孔血蓝蛋白（KLH）上。将所得糖缀合物作为小鼠中的疫苗进行评价，并与5 '-N-苯乙酰基GM 3（GM 3 NPhAc）的KLH缀合物进行比较，GM 3 NPhAc是一种高度免疫原性的GM 3衍生物，其先前作为疫苗候选物进行了研究。所有四种新的GM 3衍生物被证明比GM 3 NPhAc更具免疫原性，并引发非常强的T细胞依赖性免疫应答，这是癌症免疫治疗所需的。结论是新的GM 3衍生物可以形成有希望的疫苗候选物，其可以用于与细胞糖工程联合收割机用于癌症免疫治疗。
GM3, a sialylated trisaccharide antigen expressed by a number of tumors, is an attractive target in the design of therapeutic cancer vaccines. However, a serious problem associated with GM3 is that it is poorly immunogenic. To overcome this problem for the development of GM3-based cancer vaccines, four GM3 derivatives, including 5’-N-p-methylphenylacetyl, 5’-N-p-methoxyphenylacetyl, 5’-N-p-acetophenylacetyl and 5’-N-p-chlorophenylacetyl GM3, were synthesized and then coupled to a carrier protein, keyhole limpet haemocyanin (KLH). The resultant glycoconjugates were evaluated as vaccines in mouse and compared to the KLH conjugate of 5’-N-phenylacetyl GM3 (GM3NPhAc), a highly immunogenic GM3 derivative that was previously investigated as a vaccine candidate. All of the four new GM3 derivatives were proved to be more immunogenic than GM3NPhAc and elicit very strong T cell-dependent immune responses desirable for cancer immunotherapy. It was concluded that the new GM3 derivatives can form promising vaccine candidates that may be used to combine with cell glycoengineering for cancer immunotherapy.