Abstract
The tumor-associated antigen MUC1 is an attractive target for immunotherapy, however, its weak immunogenicity limits the induction of antitumor immune responses. To overcome this limitation, in this study, MUC1 glycopeptide was covalently linked with a diphtheria toxin-derived T-helper epitope (DT331-345). Subsequently, the resulting DT-MUC1 glycopeptide was physically mixed with natural killer T cell agonist αGalCer to explore their immunomodulatory synergy. Biological results demonstrated that compared to MUC1+αGalCer and DT-MUC1 groups, the specific IgG antibody titer of DT-MUC1+αGalCer group increased by 189- and 3-fold, respectively, indicating that the diphtheria toxin-derived T-helper epitope synergistically enhanced MUC1 immunogenicity with αGalCer. Moreover, the DT-MUC1+αGalCer vaccine induced potent cellular immune responses and significantly inhibited the growth of B16-MUC1 tumors in vivo. Furthermore, it was found that the anti-MUC1 IgG antibody titer induced by DT-MUC1+αGalCer was equivalent to that induced by palmitoylated DT-MUC1+αGalCer (P1-DT-MUC1+αGalCer) and significantly higher than that induced by doubly palmitoylated DT-MUC1+αGalCer (P2-DT-MUC1+αGalCer), suggesting that the easily synthesized DT-MUC1 may not require lipid chain modification and already possess good amphiphilicity. This is the first time that a diphtheria toxin-derived helper T-helper epitope was covalently linked to a glycopeptide antigen to enhance its immunogenicity, and this study may provide an effective vaccine design strategy for MUC1-targeted antitumor vaccines and offer novel insights into the design of fully synthetic peptide vaccines.
Published Version (
Free)
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 callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
