抗肿瘤糖疫苗研究
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- 英文论文题名：Development of Carbohydrate-Based Anti-Cancer Vaccines
- 论文作者：叶新山
- 英文论文作者：Xin-Shan Ye ; State Key Laboratory of Natural and Biomimetic Drugs ; Peking University ; and School of Pharmaceutical Sciences ; Peking University
- 年：2016
- 作者机构：北京大学天然药物及仿生药物国家重点实验室;
- 论文关键词：抗肿瘤 ; 糖疫苗 ; 结构修饰
- 会议召开时间：2016-07-01
- 会议录名称：中国化学会第30届学术年会摘要集-第二十八分会：化学生物学
- 语种：中文
- 分类号：R392-33
- 学会代码：ZGHY
- 会议名称：中国化学会第30届学术年会-第二十八分会 ; 化学生物学
- 会议地点：中国辽宁大连
- 主办单位：中国化学会
- 学会名称：中国化学会
- 页数：1
- 文件大小：134k
- 原文格式：D
- 会议级别：全国
摘要
肿瘤相关糖抗原是抗肿瘤疫苗研究的重要靶标。但糖抗原通常免疫原性很弱,难以诱发有效的免疫应答。因此,打破免疫系统对肿瘤细胞表面高度表达的肿瘤相关糖抗原的免疫耐受是抗肿瘤糖疫苗能否成功的关键。针对天然STn糖抗原免疫原性弱的问题,我们基于STn的结构,分别在唾液酸的氮原子位置和氨基半乳糖的氮原子位置对天然STn抗原进行一系列结构修饰,合成了STn糖抗原衍生物库,经筛选和小鼠动物体内评价,发现其中某些修饰糖抗原与KLH的偶联物可以增强免疫原性,可刺激小鼠产生高效价的抗体,并且和天然糖抗原有较强的交叉反应,而且小鼠免疫后的血清能够识别表达天然STn抗原的肿瘤细胞。进一步用小鼠肿瘤模型进行实验,发现修饰糖疫苗可延长肿瘤小鼠的生存期。这些工作为抗肿瘤糖疫苗的研究提供了新的路径。
Tumor-associated carbohydrate antigens(TACAs) are regarded as important targets for vaccine development.Vaccines based on synthetic oligosaccharide antigens against cancers are at different stages of preclinical and clinical studies.However,carbohydrate antigens pose weak immunogenicity,since they are self-antigens and consequently tolerated by the immune system.Various efforts have been made to break the immuno-tolerance.Although advances have been achieved in this field,approaches to enhancement of the immunogenicity of carbohydrate antigens are still in great demand.To solve this problem,we designed and synthesized some structurally-modified carbohydrate antigens.These synthetic antigens were immunologically screened in vitro by using competitive ELISA method,and the antigens with positive response were conjugated to protein carrier for vaccination.The vaccination results on mice showed that some fluorine-containing modifications on carbohydrate antigens can significantly increase the IgG titers and improve the ratios of IgG/IgM.,and the antisera can recognize the tumor cells expressing the native carbohydrate antigen.
Tumor-associated carbohydrate antigens(TACAs) are regarded as important targets for vaccine development.Vaccines based on synthetic oligosaccharide antigens against cancers are at different stages of preclinical and clinical studies.However,carbohydrate antigens pose weak immunogenicity,since they are self-antigens and consequently tolerated by the immune system.Various efforts have been made to break the immuno-tolerance.Although advances have been achieved in this field,approaches to enhancement of the immunogenicity of carbohydrate antigens are still in great demand.To solve this problem,we designed and synthesized some structurally-modified carbohydrate antigens.These synthetic antigens were immunologically screened in vitro by using competitive ELISA method,and the antigens with positive response were conjugated to protein carrier for vaccination.The vaccination results on mice showed that some fluorine-containing modifications on carbohydrate antigens can significantly increase the IgG titers and improve the ratios of IgG/IgM.,and the antisera can recognize the tumor cells expressing the native carbohydrate antigen.
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