1. Synthesis and immunological evaluation of MUC1 glycopeptide conjugates bearing N-acetyl modified STn derivatives as anticancer vaccines.
- Author
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Xiao A, Zheng XJ, Song C, Gui Y, Huo CX, and Ye XS
- Subjects
- Animals, Antigens, Tumor-Associated, Carbohydrate metabolism, Cancer Vaccines pharmacology, Cell Line, Tumor, Female, Glycopeptides immunology, Hemocyanins immunology, Humans, Immune Sera chemistry, Immune Sera immunology, Immunization, Mice, Mice, Inbred BALB C, Mucin-1 chemistry, Neoplasms prevention & control, Antigens, Tumor-Associated, Carbohydrate immunology, Glycopeptides chemical synthesis, Glycopeptides pharmacology, Hemocyanins chemical synthesis, Hemocyanins pharmacology
- Abstract
Glycoprotein MUC1 is an attractive target for anti-tumor vaccine development. However, the weak immunogenicity of MUC1 remains a significant problem. To solve this problem, several STn derivatives with N-acetyl modifications were synthesized and incorporated into a 20-amino acid MUC1 tandem repeat sequence. The modified STn-MUC1 glycopeptides were further connected to a carrier protein keyhole limpet hemocyanin (KLH). The immunological effects of these synthetic vaccine conjugates were evaluated using the BALB/c mouse model. The results showed that vaccine V2 elicited higher titers of antibodies which cross-reacted with the native STn-MUC1 antigen. Moreover, the elicited antisera reacted with the STn-MUC1 antigen-positive tumor cells, indicating that the carbohydrate antigen modification strategy may hold potential to overcome the weak immunogenicity of natural MUC1 glycopeptides.
- Published
- 2016
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