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Synthesis and immunological evaluation of N-acyl modified Tn analogues as anticancer vaccine candidates
Affiliation:1. School of Life Sciences, Northeast Normal University, Changchun 130024, PR China;2. State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Xue Yuan Road No. 38, Beijing 100191, PR China;1. State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Xue Yuan Road No. 38, Beijing 100191, China;2. National Engineering Research Center for Carbohydrate Synthesis, Jiangxi Normal University, Nanchang 330022, Jiangxi, China;1. State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Xue Yuan Road No. 38, Beijing 100191, China;2. National Engineering Research Center for Carbohydrate Synthesis, Jiangxi Normal University, Nanchang 330022, Jiangxi, China;1. College of Food Science and Technology, Hunan Agricultural University, Changsha 410128, Hunan Province, China;2. State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China;3. School of Public Healthy, Xiangnan University, Chenzhou 423000, Hunan Province, China
Abstract:Tumor-associated carbohydrate antigens (TACAs), which are aberrantly expressed on the surface of tumor cells, are important targets for anticancer vaccine development. Herein, several N-acyl modified Tn analogues were synthesized and conjugated with carrier protein CRM197. The immunological results of these glycoconjugates indicated that 6–CRM197 elicited higher titers of antibodies which cross-reacted with native Tn antigen than the unmodified 2–CRM197 did. The IFN-γ-producing frequency of lymphocytes in mice treated with 6–CRM197 was obviously increased, compared to that of mice vaccinated with 2–CRM197 (p = 0.016), which was typically associated with the Th1 response. Moreover, the elicited antisera against antigen 6–CRM197 reacted strongly with the Tn-positive tumor cells, implying the potential of this glycoconjugate as an anticancer vaccine.
Keywords:Carbohydrate  Vaccine  Tn antigen  Glycoconjugate  Anticancer
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