Progression of pancreatic adenocarcinoma is significantly impeded with a combination of vaccine and COX-2 inhibition

Pinku Mukherjee, Gargi D. Basu, Teresa L. Tinder, Durai B. Subramani, Judy M. Bradley, Million Arefayene, Todd Skaar, Giovanni De Petris

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81 Scopus citations

Abstract

With a 5-year survival rate of <5%, pancreatic cancer is one of the most rapidly fatal malignancies. Current protocols for the treatment of pancreas cancer are not as effective as we desire. In this study, we show that a novel Mucin-1 (MUC1)-based vaccine in combination with a cyclooxygenase-2 inhibitor (celecoxib), and low-dose chemotherapy (gemcitabine) was effective in preventing the progression of preneoplastic intraepithelial lesions to invasive pancreatic ductal adenocarcinomas. The study was conducted in an appropriate triple transgenic model of spontaneous pancreatic cancer induced by the KRAS G12D mutation and that expresses human MUC1 as a self molecule. The combination treatment elicited robust antitumor cellular and humoral immune responses and was associated with increased apoptosis in the tumor. The mechanism for the increased immune response was attributed to the down-regulation of circulating prostaglandin E2 and indoleamine 2, 3,-dioxygenase enzymatic activity, as well as decreased levels of T regulatory and myeloid suppressor cells within the tumor microenvironment. The preclinical data provide the rationale to design clinical trials with a combination of MUC1-based vaccine, celecoxib, and gemcitabine for the treatment of pancreatic cancer.

Original languageEnglish (US)
Pages (from-to)216-224
Number of pages9
JournalJournal of Immunology
Volume182
Issue number1
DOIs
StatePublished - Jan 1 2009

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Mukherjee, P., Basu, G. D., Tinder, T. L., Subramani, D. B., Bradley, J. M., Arefayene, M., Skaar, T., & De Petris, G. (2009). Progression of pancreatic adenocarcinoma is significantly impeded with a combination of vaccine and COX-2 inhibition. Journal of Immunology, 182(1), 216-224. https://doi.org/10.4049/jimmunol.182.1.216