【作者】 叶新山；

【Author】 Xin-Shan Ye;State Key Laboratory of Natural and Biomimetic Drugs,School of Pharmaceutical Sciences,Peking University;

【机构】 北京大学；

【摘要】 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 structurallymodified 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 suitable 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.Furthermore,the antitumor ability of the vaccines was also investigated in a murine model of colon cancer.In addition,the mechanism of tumor immunotherapy of the vaccines was explored preliminarily.更多还原

【Abstract】 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 structurallymodified 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 suitable 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.Furthermore,the antitumor ability of the vaccines was also investigated in a murine model of colon cancer.In addition,the mechanism of tumor immunotherapy of the vaccines was explored preliminarily.更多还原