Synthetic multivalent glycopeptide-lipopeptide antitumor vaccines: impact of the cluster effect on the killing of tumor cells

Angew Chem Int Ed Engl. 2014 Feb 3;53(6):1699-703. doi: 10.1002/anie.201308875. Epub 2014 Jan 21.

Abstract

Multivalent synthetic vaccines were obtained by solid-phase synthesis of tumor-associated MUC1 glycopeptide antigens and their coupling to a Pam3 Cys lipopeptide through click reactions. These vaccines elicited immune responses in mice without the use of any external adjuvant. The vaccine containing four copies of a MUC1 sialyl-TN antigen showed a significant cluster effect. It induced in mice prevailing IgG2a antibodies, which bind to MCF-7 breast tumor cells and initiate the killing of these tumor cells by activation of the complement-dependent cytotoxicity complex.

Keywords: antigens; antitumor agents; cytotoxicity; multivalent glycopeptides; vaccines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies / immunology
  • Antibodies / pharmacology
  • Apoptosis / drug effects
  • Cancer Vaccines / chemical synthesis
  • Cancer Vaccines / chemistry
  • Cancer Vaccines / immunology*
  • Click Chemistry
  • Epitopes, T-Lymphocyte / chemistry
  • Epitopes, T-Lymphocyte / immunology
  • Glycopeptides / chemical synthesis
  • Glycopeptides / chemistry*
  • Humans
  • Lipoproteins / chemical synthesis
  • Lipoproteins / chemistry*
  • MCF-7 Cells
  • Mice
  • Mice, Inbred BALB C
  • Mucin-1 / chemistry*
  • Mucin-1 / immunology
  • Mucin-1 / metabolism
  • Rabbits

Substances

  • Antibodies
  • Cancer Vaccines
  • Epitopes, T-Lymphocyte
  • Glycopeptides
  • Lipoproteins
  • Mucin-1
  • N-palmitoyl-S-(2,3-bis(palmitoyloxy)propyl)cysteinyl-seryl-lysyl-lysyl-lysyl-lysine