Abstract
Aberrantly glycosylated Mucin 1 (MUC1) is frequently over-expressed in epithelial cancers, making it an attractive target for cancer vaccines. Over the past two decades, multiple MUC1-based vaccines have been investigated clinically, yet they have generally shown limited efficacy due to challenges such as low immunogenicity, difficulty in overcoming immune tolerance, and potential issues related to glycosylation effects and antigen presentations. To advance the understanding of MUC1 vaccines, we report an efficient chemo-enzymatic approach for the preparation of four MUC1 antigen variants with different glycoforms through liquid-phase glycopeptide synthesis. These antigen were conjugated with CRM197 to generate various glycopeptide-protein conjugate vaccines, and their immunogenicity was evaluated based on total and subtype antibody titers, binding affinity, complement-dependent cytotoxicity (CDC) activity, and antibody-dependent cellular phagocytosis (ADCP). The combination of MPL and QS21 adjuvants with STn-MUC1-CRM197 conjugate induced a potent Th1-biased immune response, evidenced by elevating IgG2a titers and stronger antibody binding to MCF-7 cells. This formulation demonstrated superior CDC activity, ADCP activity and binding affinity to human breast cancer tissues in immuno-histochemical assays. The synergistic effect of specific adjuvants and glycosylated MUC1 conjugates offers a strategic avenue for MUC1 cancer vaccine development.
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call