Immune and anticancer responses elicited by fully synthetic aberrantly glycosylated MUC1 tripartite vaccines modified by a TLR2 or TLR9 agonist

Abu Baker M Abdel-Aal, Vani Lakshminarayanan, Pamela Thompson, Nitin Supekar, Judy M. Bradley, Margreet A. Wolfert, Peter A Cohen, Sandra J Gendler, Geert Jan Boons

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

The mucin MUC1 is overexpressed and aberrantly glycosylated by many epithelial cancer cells manifested by truncated O-linked saccharides. Although tumor-associated MUC1 has generated considerable attention because of its potential for the development of a therapeutic cancer vaccine, it has been difficult to design constructs that consistently induce cytotoxic T-lymphocytes (CTLs) and ADCC-mediating antibodies specific for the tumor form of MUC1. We have designed, chemically synthesized, and immunologically examined vaccine candidates each composed of a glycopeptide derived from MUC1, a promiscuous Thelper peptide, and a TLR2 (Pam3CysSK4) or TLR9 (CpG-ODN 1826) agonist. It was found that the Pam3CysSK 4-containing compound elicits more potent antigenic and cellular immune responses, resulting in a therapeutic effect in a mouse model of mammary cancer. It is thus shown, for the first time, that the nature of an inbuilt adjuvant of a tripartite vaccine can significantly impact the quality of immune responses elicited against a tumor-associated glycopeptide. The unique adjuvant properties of Pam3CysSK4, which can reduce the suppressive function of regulatory T cells and enhance the cytotoxicity of tumor-specific CTLs, are likely responsible for the superior properties of the vaccine candidate 1.

Original languageEnglish (US)
Pages (from-to)1508-1513
Number of pages6
JournalChemBioChem
Volume15
Issue number10
DOIs
StatePublished - Jul 7 2014

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Keywords

  • adjuvants
  • cancer
  • carbohydrates
  • mucins
  • peptides
  • vaccines

ASJC Scopus subject areas

  • Biochemistry
  • Organic Chemistry
  • Molecular Medicine
  • Molecular Biology
  • Medicine(all)

Cite this

Abdel-Aal, A. B. M., Lakshminarayanan, V., Thompson, P., Supekar, N., Bradley, J. M., Wolfert, M. A., Cohen, P. A., Gendler, S. J., & Boons, G. J. (2014). Immune and anticancer responses elicited by fully synthetic aberrantly glycosylated MUC1 tripartite vaccines modified by a TLR2 or TLR9 agonist. ChemBioChem, 15(10), 1508-1513. https://doi.org/10.1002/cbic.201402077