Synthesis and immunological evaluation of MUC1 glycopeptide conjugates bearing N-acetyl modified STn derivatives as anticancer vaccines
| Autor: | Chengcheng Song, Xiu-Jing Zheng, An Xiao, Xin-Shan Ye, Yue Gui, Chang-Xin Huo |
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| Rok vydání: | 2016 |
| Předmět: |
Synthetic vaccine
010402 general chemistry Cancer Vaccines digestive system 01 natural sciences Biochemistry Mice Antigen Cell Line Tumor Neoplasms Animals Humans Antigens Tumor-Associated Carbohydrate Physical and Theoretical Chemistry skin and connective tissue diseases neoplasms MUC1 chemistry.chemical_classification Mice Inbred BALB C biology 010405 organic chemistry Chemistry Immune Sera Immunogenicity Mucin-1 Organic Chemistry Glycopeptides digestive system diseases biological factors Glycopeptide 0104 chemical sciences Hemocyanins biology.protein Female Immunization Antibody Glycoprotein Keyhole limpet hemocyanin |
| Zdroj: | Organic & Biomolecular Chemistry. 14:7226-7237 |
| ISSN: | 1477-0539 1477-0520 |
| DOI: | 10.1039/c6ob01092j |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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