Synthesis and Immunological Evaluation of a Single Molecular Construct MUC1 Vaccine Containing l-Rhamnose Repeating Units

Molecules. 2020 Jul 9;25(14):3137. doi: 10.3390/molecules25143137.

Abstract

A rhamnose targeting strategy for generating effective anticancer vaccines was successful in our previous studies. We showed that by utilizing natural anti-rhamnose antibodies, a rhamnose-containing vaccine can be targeted to antigen-presenting cells, such as dendritic cells. In this case, rhamnose (Rha) was linked directly to the liposomes bearing the antigen. However, in the current approach, we conjugated a multivalent Tri-Rha ligand with the antigen itself, making it a single component vaccine construct, unlike the previous two-component vaccine construct where Rha cholesterol and Mucin1 (MUC1) antigen were both linked separately to the liposomes. Synthesis required the development of a linker for coupling of the Rha-Ser residues. We compared those two systems in a mouse model and found increased production of anti-MUC1 antibodies and more primed antigen-specific CD4+ T cells in both of the targeted approaches when compared to the control group, suggesting that this one-component vaccine construct could be a potential design used in our MUC1 targeting mechanisms.

Keywords: MUC1; anti-rhamnose antibodies; cancer immunotherapy; cancer vaccine; liposomes; rhamnose.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology*
  • Cancer Vaccines* / chemistry
  • Cancer Vaccines* / immunology
  • Cancer Vaccines* / pharmacology
  • Dendritic Cells / immunology*
  • Female
  • Liposomes
  • Mice
  • Mucin-1* / chemistry
  • Mucin-1* / immunology
  • Mucin-1* / pharmacology
  • Rhamnose* / chemistry
  • Rhamnose* / immunology
  • Rhamnose* / pharmacology

Substances

  • Cancer Vaccines
  • Liposomes
  • MUC1 protein, human
  • Mucin-1
  • Rhamnose