Enhanced immunogenicity of multivalent MUC1 glycopeptide antitumour vaccines based on hyperbranched polymers

Org Biomol Chem. 2015 Oct 28;13(40):10150-4. doi: 10.1039/c5ob01255d. Epub 2015 Aug 24.

Abstract

Enhancing the immunogenicity of an antitumour vaccine still poses a major challenge. It depends upon the selected antigen and the mode of its presentation. We here describe a fully synthetic antitumour vaccine, which addresses both aspects. For the antigen, a tumour-associated MUC1 glycopeptide as B-cell epitope was synthesised and linked to the immunostimulating T-cell epitope P2 derived from tetanus toxoid. The MUC1-P2 conjugate is presented multivalently on a hyperbranched polyglycerol to the immune system. In comparison to a related vaccine of lower multivalency, this vaccine exposing more antigen structures on the hyperbranched polymer induced significantly stronger immune responses in mice and elicited IgG antibodies of distinctly higher affinity to epithelial tumour cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cancer Vaccines / chemistry
  • Cancer Vaccines / genetics
  • Cancer Vaccines / immunology*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Glycerol / chemistry
  • Glycerol / immunology*
  • Glycopeptides / chemistry
  • Glycopeptides / genetics
  • Glycopeptides / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Molecular Structure
  • Mucin-1 / chemistry
  • Mucin-1 / genetics
  • Mucin-1 / immunology*
  • Polymers / chemistry

Substances

  • Cancer Vaccines
  • Glycopeptides
  • Mucin-1
  • Polymers
  • polyglycerol
  • Glycerol