Jump to main content
Jump to site search

Issue 10, 2013
Previous Article Next Article

The development of synthetic antitumour vaccines from mucin glycopeptide antigens

Author affiliations

Abstract

Based on important cell-biological and biochemical results concerning the structural difference between membrane glycoproteins of normal epithelial cells and epithelial tumour cells, tumour-associated glycopeptide antigens have been chemically synthesised and structurally confirmed. Glycopeptide structures of the tandem repeat sequence of mucin MUC1 of epithelial tumour cells constitute the most promising tumour-associated antigens. In order to generate a sufficient immunogenicity of these endogenous structures, usually tolerated by the immune system, these synthetic glycopeptide antigens were conjugated to immune stimulating components: in fully synthetic two-component vaccines either with T-cell peptide epitopes or with Toll-like receptor2 lipopeptide ligands or in three-component vaccines with both these stimulants. Alternatively, the synthetic glycopeptide antigens were coupled to immune stimulating carrier proteins. In particular, MUC1 glycopeptide conjugates with Tetanus toxoid proved to be efficient vaccines inducing very strong immune responses in mice. The antibodies elicited with the fully synthetic vaccines showed selective recognition of the tumour-associated glycopeptides as was shown by neutralisation and micro-array binding experiments. After booster immunisations, most of the immune responses showed the installation of an immunological memory. Immunisation with fully synthetic three-component vaccines induced immune reactions with therapeutic effects in terms of reduction of the tumour burden in mice or in killing of tumour cells in culture, while MUC1 glycopeptide–Tetanus toxoid vaccines elicited antibodies in mice which recognised tumour cells in human tumour tissues. The results achieved so far are considered to be promising for the development of an active immunisation against tumours.

Graphical abstract: The development of synthetic antitumour vaccines from mucin glycopeptide antigens

Back to tab navigation

Publication details

The article was received on 19 Nov 2012 and first published on 25 Feb 2013


Article type: Review Article
DOI: 10.1039/C3CS35470A
Citation: Chem. Soc. Rev., 2013,42, 4421-4442
  •   Request permissions

    The development of synthetic antitumour vaccines from mucin glycopeptide antigens

    N. Gaidzik, U. Westerlind and H. Kunz, Chem. Soc. Rev., 2013, 42, 4421
    DOI: 10.1039/C3CS35470A

Search articles by author

Spotlight

Advertisements