Synthesis and Immunological Evaluation of a Multicomponent Cancer Vaccine Candidate Containing a Long MUC1 Glycopeptide

Nitin T. Supekar, Vani Lakshminarayanan, Chantelle J. Capicciotti, Anju Sirohiwal, Cathy S. Madsen, Margreet A. Wolfert, Peter A Cohen, Sandra J Gendler, Geert Jan Boons

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

A fully synthetic MUC1-based cancer vaccine was designed and chemically synthesized containing an endogenous helper T-epitope (MHC classII epitope). The vaccine elicited robust IgG titers that could neutralize cancer cells by antibody-dependent cell-mediated cytotoxicity (ADCC). It also activated cytotoxic T-lymphocytes. Collectively, the immunological data demonstrate engagement of helper T-cells in immune activation. A synthetic methodology was developed for a penta-glycosylated MUC1 glycopeptide, and antisera of mice immunized by the new vaccine recognized such a structure. Previously reported fully synthetic MUC1-based cancer vaccines that elicited potent immune responses employed exogenous helper T-epitopes derived from microbes. It is the expectation that the use of the newly identified endogenous helper T-epitope will be more attractive, because it will activate cognate CD4+ T-cells that will provide critical tumor-specific help intratumorally during the effector stage of tumor rejection and will aid in the generation of sustained immunological memory.

Original languageEnglish (US)
JournalChemBioChem
DOIs
StateAccepted/In press - Jan 1 2017

Keywords

  • Cancer
  • Endogenous helper
  • Glycopeptide
  • Multicomponent vaccine
  • T-epitope

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Organic Chemistry

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    Supekar, N. T., Lakshminarayanan, V., Capicciotti, C. J., Sirohiwal, A., Madsen, C. S., Wolfert, M. A., Cohen, P. A., Gendler, S. J., & Boons, G. J. (Accepted/In press). Synthesis and Immunological Evaluation of a Multicomponent Cancer Vaccine Candidate Containing a Long MUC1 Glycopeptide. ChemBioChem. https://doi.org/10.1002/cbic.201700424