Zheng Xiu-Jing, Yang Fan, Zheng Mingwei, Huo Chang-Xin, Zhang Ye, Ye Xin-Shan
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, and Center for Molecular and Translational Medicine, Peking University, Xue Yuan Rd No. 38, Beijing 100191, China.
Org Biomol Chem. 2015 Jun 14;13(22):6399-406. doi: 10.1039/c5ob00405e.
Tumor cells often display aberrant levels and patterns of cell surface glycosylation, which provides a potential opportunity to develop carbohydrate-based anticancer vaccines for cancer immunotherapy. However, one of the most addressed challenges in this field is the low efficiency of the carbohydrate vaccination due to poor immunogenicity of carbohydrate antigens. In this article, a number of structure-modified GM3 antigen analogues were designed and chemically synthesized. The modified GM3 antigens were conjugated to protein carriers for vaccination. The vaccination results on mice show that the modification on the GM3 antigen could improve the efficiency of the vaccination, and in particular, two glycoconjugates (3-KLH and 8-KLH) elicited higher titers of anti-GM3 antibodies than the unmodified GM3-protein conjugate (2-KLH) did.
肿瘤细胞常常表现出细胞表面糖基化水平和模式异常,这为开发基于碳水化合物的抗癌疫苗用于癌症免疫治疗提供了潜在机会。然而,该领域最受关注的挑战之一是由于碳水化合物抗原免疫原性较差,导致碳水化合物疫苗接种效率低下。在本文中,设计并化学合成了多种结构修饰的GM3抗原类似物。将修饰后的GM3抗原与蛋白质载体偶联用于疫苗接种。对小鼠的疫苗接种结果表明,GM3抗原上的修饰可提高疫苗接种效率,特别是两种糖缀合物(3-KLH和8-KLH)诱导产生的抗GM3抗体滴度高于未修饰的GM3-蛋白质偶联物(2-KLH)。