Cancer is one of the most dangerous diseases which kill millions of people around the world annually. With the fast developing of immunology, the immunotherapy of cancer became the most promising way against tumor. But choosing a sufficient tumor-specific antigen is the critical prerequisite for developing an effectively antitumor vaccine. MUC1 protein is a member of mucin family which is over-expressed and aberrantly glycosylated in most epithelial tumor cells. So MUC1 tandem repeat sequences peptide combined with tumor-associated carbohydrates antigens (TACAs) seems to be an attractive antitumor target.However, because of the low immunogenicity of MUC1 peptide, new strategies should be considered to design more effective vaccines to elicit sufficient immune responses. Pam3CSK4 is the agonist of TLR2 which can effectively activate the innate immune system andconsequently activate the adaptive immune system.It is reported that the multivalent antigen vaccine could elicit stronger immune response than single antigen by cluster effect. So we conjugated the multivalent MUC1 glycopeptideantigen to TLR2 ligand lipopeptideby click chemistry.[1]This vaccine consisting of four copies of MUC1-TACA antigen produced a significant cluster effect and elicited strong immune response without any extra adjuvant. The antibodies induced by the vaccine in micewere prevailing IgG2a which meant the vaccine elicited mainly Th1 cell mediating cellular immune response against tumor cell.References: [1]. HuiCai, Zhan-Yi Sun, Mei-Sha Chen, Yu-Fen Zhao, Horst Kunz and Yan-Mei Li, Synthetic Multivalent Glycopeptide-Lipopeptide Antitumor Vaccines: Impact of the Cluster Effect on the Killing of Tumor Cells, Angew. Chem. Int. Ed. 2014, 53  , 1 � 6.

Fully Synthetic Multivalent Glycopeptide-Based Antitumor Vaccines

248th National Meeting (2014)

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