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Synthesis and Evaluation of Glycoconjugates Comprising N ‐Acyl‐Modified Thomsen–Friedenreich Antigens as Anticancer Vaccines
Author(s) -
Sun Shuang,
Zheng XiuJing,
Huo ChangXin,
Song Chengcheng,
Li Qin,
Ye XinShan
Publication year - 2016
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201600094
Subject(s) - glycoconjugate , antigen , immunogenicity , diphtheria toxin , cytotoxicity , conjugate , conjugate vaccine , toxoid , chemistry , antibody , hapten , microbiology and biotechnology , biology , immunology , biochemistry , immunization , in vitro , toxin , mathematical analysis , mathematics
Thomsen–Friedenreich (TF) antigen is an important tumor‐associated carbohydrate antigen. Its low immunogenicity, however, limits its application in the development of anticancer vaccines. To solve this problem, several N ‐acyl‐modified TF derivatives were synthesized and conjugated with carrier protein CRM197 (a mutated diphtheria toxoid cross‐reactive material). The immunological results in BALB/c mice demonstrated that these modified TF antigen conjugates could stimulate the production of higher titers of IgG antibodies that cross‐reacted with native TF antigen. These glycoconjugates showed strong lymphocyte proliferative response, suggesting that they can induce cellular immunity. Furthermore, the elicited antisera reacted strongly with TF‐positive tumor cells (4T1). In particular, the N ‐monofluoroacetyl‐modified TF conjugate 4 ‐CRM197 showed the strongest complement‐dependent cytotoxicity effect against 4T1 cells, implying the potential of this glycoconjugate as an anticancer vaccine.