Synthesis and immunological evaluation of N-acyl modified Tn analogues as anticancer vaccine candidates

• Published in: Bioorganic & medicinal chemistry 2016-02, Vol.24 (4), p.915-920
• Main Authors: Song, Chengcheng, Sun, Shuang, Huo, Chang-Xin, Li, Qin, Zheng, Xiu-Jing, Tai, Guihua, Zhou, Yifa, Ye, Xin-Shan
• Format: Article
• Language: English
• Subjects: Acylation; Animals; Antibodies, Neoplasm - biosynthesis; Anticancer; Antigens, Tumor-Associated, Carbohydrate - chemistry; Antigens, Tumor-Associated, Carbohydrate - immunology; Bacterial Proteins - administration & dosage; Bacterial Proteins - chemistry; Bacterial Proteins - immunology; Cancer Vaccines - administration & dosage; Cancer Vaccines - chemistry; Cancer Vaccines - immunology; Carbohydrate; Diphtheria Toxin - administration & dosage; Diphtheria Toxin - chemistry; Diphtheria Toxin - immunology; Female; Glycoconjugate; Glycoconjugates - administration & dosage; Glycoconjugates - chemical synthesis; Glycoconjugates - immunology; Humans; Immune Sera - chemistry; Immunity, Humoral - drug effects; Immunoglobulin G - biosynthesis; Interferon-gamma - biosynthesis; Jurkat Cells; MCF-7 Cells; Mice; Mice, Inbred BALB C; Th1 Cells - drug effects; Th1 Cells - immunology; Tn antigen; Vaccine
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2016.01.015

[Display omitted] 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.