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 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

19 Citations (Scopus)

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

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Transgenic Mice
Tumors
Vaccines
genetically modified organisms
peptides
vaccines
T-cells
Peptides
neoplasms
mice
Growth
T-Lymphocytes
T-lymphocytes
Neoplasms
Vaccination
synthetic peptides
vaccination
Tumor Escape
Neoplasm Antigens
Interferon-gamma

ASJC Scopus subject areas

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

Cite this

MUC1 vaccines, comprised of glycosylated or non-glycosylated peptides or tumor-derived MUC1, can circumvent immunoediting to control tumor growth in MUC1 transgenic mice. / Lakshminarayanan, Vani; Supekar, Nitin T.; Wei, Jie; McCurry, Dustin B.; Dueck, Amylou; Kosiorek, Heidi E.; Trivedi, Priyanka P.; Bradley, Judy M.; Madsen, Cathy S.; Pathangey, Latha B.; Hoelzinger, Dominique B.; Wolfert, Margreet A.; Boons, Geert Jan; Cohen, Peter A; Gendler, Sandra J.

In: PLoS One, Vol. 11, No. 1, e0145920, 01.01.2016.

Research output: Contribution to journalArticle

Lakshminarayanan, V, Supekar, NT, Wei, J, McCurry, DB, Dueck, A, Kosiorek, HE, Trivedi, PP, Bradley, JM, Madsen, CS, Pathangey, LB, Hoelzinger, DB, Wolfert, MA, Boons, GJ, Cohen, PA & Gendler, SJ 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, vol. 11, no. 1, e0145920. https://doi.org/10.1371/journal.pone.0145920
Lakshminarayanan, Vani ; Supekar, Nitin T. ; Wei, Jie ; McCurry, Dustin B. ; Dueck, Amylou ; Kosiorek, Heidi E. ; Trivedi, Priyanka P. ; Bradley, Judy M. ; Madsen, Cathy S. ; Pathangey, Latha B. ; Hoelzinger, Dominique B. ; Wolfert, Margreet A. ; Boons, Geert Jan ; Cohen, Peter A ; Gendler, Sandra J. / MUC1 vaccines, comprised of glycosylated or non-glycosylated peptides or tumor-derived MUC1, can circumvent immunoediting to control tumor growth in MUC1 transgenic mice. In: PLoS One. 2016 ; Vol. 11, No. 1.
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