MUC1 vaccines, comprised of glycosylated or non-glycosylated peptides or tumor-derived MUC1, can circumvent immunoediting to control tumor growth in MUC1 transgenic mice

Vani Lakshminarayanan, Nitin T. Supekar, Jie Wei, Dustin B. McCurry, Amylou C. Dueck, Heidi E. Kosiorek, Priyanka P. Trivedi, Judy M. Bradley, Cathy S. Madsen, Latha B. Pathangey, Dominique B. Hoelzinger, Margreet A. Wolfert, Geert Jan Boons, Peter A. Cohen, Sandra J. Gendler

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

It remains challenging to produce decisive vaccines against MUC1, a tumor-Associated antigen widely expressed by pancreas, breast and other tumors. Employing clinically relevant mouse models, we ruled out such causes as irreversible T-cell tolerance, inadequate avidity, and failure of T-cells to recognize aberrantly glycosylated tumor MUC1. Instead, every tested MUC1 preparation, even non-glycosylated synthetic 9mer peptides, induced interferon gamma-producing CD4+ and CD8+ T-cells that recognized glycosylated variants including tumor-Associated MUC1. Vaccination with synthetic peptides conferred protection as long as vaccination was repeated post tumor challenge. Failure to revaccinate post challenge was associated with down-regulated tumor MUC1 and MHC molecules. Surprisingly, direct admixture of MUC1-expressing tumor with MUC1-hyperimmune T-cells could not prevent tumor outgrowth or MUC1 immunoediting, whereas ex vivo activation of the hyperimmune T-cells prior to tumor admixture rendered them curative. Therefore, surrogate T-cell preactivation outside the tumor bed, either in culture or by repetitive vaccination, can overcome tumor escape.

Original languageEnglish (US)
Article numbere0145920
JournalPloS one
Volume11
Issue number1
DOIs
StatePublished - Jan 1 2016

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Lakshminarayanan, V., Supekar, N. T., Wei, J., McCurry, D. B., Dueck, A. C., Kosiorek, H. E., Trivedi, P. P., Bradley, J. M., Madsen, C. S., Pathangey, L. B., Hoelzinger, D. B., Wolfert, M. A., Boons, G. J., Cohen, P. A., & Gendler, S. J. (2016). MUC1 vaccines, comprised of glycosylated or non-glycosylated peptides or tumor-derived MUC1, can circumvent immunoediting to control tumor growth in MUC1 transgenic mice. PloS one, 11(1), [e0145920]. https://doi.org/10.1371/journal.pone.0145920