A fully synthetic four-component antitumor vaccine consisting of a mucin glycopeptide antigen combined with three different T-helper-cell epitopes

Angew Chem Int Ed Engl. 2014 Dec 15;53(51):14245-9. doi: 10.1002/anie.201406843. Epub 2014 Oct 15.

Abstract

In a new concept of fully synthetic vaccines, the role of T-helper cells is emphasized. Here, a synthetic antitumor vaccine consisting of a diglycosylated tumor-associated MUC1 glycopeptide as the B-cell epitope was covalently cross-linked with three different T-helper-cell epitopes via squaric acid ligation of two linear (glyco)peptides. In mice this four-component vaccine administered without external immune-stimulating promoters elicit titers of MUC1-specific antibodies that were about eight times higher than those induced by a vaccine containing only one T-helper-cell epitope. The promising results indicate that multiple activation of different T-helper cells is useful for applications in which increased immunogenicity is required. In personalized medicine, in particular, this flexible construction of a vaccine can serve as a role model, for example, when T-helper-cell epitopes are needed that match human leukocyte antigens (HLA) in different patients.

Keywords: T-cell epitopes; antigen presentation; antitumor vaccines; glycopeptides; tumor cell recognition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigen-Antibody Reactions
  • Antigens, Neoplasm / chemistry*
  • Antigens, Neoplasm / immunology
  • Cancer Vaccines / chemical synthesis*
  • Cancer Vaccines / chemistry
  • Cancer Vaccines / immunology
  • Epitopes / chemistry*
  • Epitopes / immunology
  • Glycopeptides / chemistry*
  • Glycopeptides / immunology
  • Humans
  • Molecular Structure
  • Mucin-1 / chemistry*
  • Mucin-1 / immunology
  • T-Lymphocytes, Helper-Inducer / chemistry*
  • T-Lymphocytes, Helper-Inducer / immunology

Substances

  • Antigens, Neoplasm
  • Cancer Vaccines
  • Epitopes
  • Glycopeptides
  • Mucin-1