Synthesis and immunological evaluation of MUC1 glycopeptide conjugates bearing N-acetyl modified STn derivatives as anticancer vaccines

Glycoprotein MUC1is an attractive target for anti-tumor vaccine development. However, the weak immunogenicityof MUC1remains 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 repeatsequence. The modified STn- MUC1 glycopeptideswere further connected to a carrier protein keyhole limpet hemocyanin(KLH). The immunological effects of these synthetic vaccineconjugates 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- MUC1antigen. Moreover, the elicited antisera reacted with the STn- MUC1antigen-positive tumor cells, indicating that the carbohydrate antigen modification strategy may hold potential to overcome the weak immunogenicityof natural MUC1 glycopeptides.