Abstract 1575: A dual immunostimulatory strategy for pancreatic cancer treatment: MUC1 cytoplasmic tail peptide therapeutic vaccine with adjuvant TLR3 agonist poly(I:C12U)

Abstract

Abstract Immunotherapy directed against MUC1, a membrane-bound mucin, may be a treatment option for pancreatic cancer patients. MUC1 is overexpressed and differentially glycosylated and phosphorylated by pancreatic cancer cells and is thus a candidate antigenic target for a therapeutic vaccine. Vaccination studies using full length MUC1 cytoplasmic tail (MUC1-CT) peptide in vivo showed an increase in median survival of C57BL/6 mice transgenic for and immunologically tolerant to MUC1 (MUC1.Tg) challenged with a syngeneic murine pancreatic tumor cell line (Panc02.MUC1) as compared to nonvaccinated controls. In a recent study, we employed an immunostimulatory adjuvant in concert with MUC1-CT peptide to improve immune system mobilization in MUC1-tolerant animals thereby enhancing the therapeutic effect of vaccination. The chosen adjuvant, poly(I:C12U), is a clinically tested GMP-grade dsRNA molecule capable of activating Toll-like receptor 3 (TLR3) present on endocytic vesicles in antigen presenting cells (APC). Agonizing TLR3 induces dendritic cell maturation in vitro and in vivo, leading to increased antigen presentation and cytokine production that prompt an antigen-specific T cell response. We hypothesized that a dual immunostimulatory strategy pairing TLR3 agonist-mediated APC activation with tolerance-breaking MUC1-CT antigen-directed vaccination would lead to directed destruction of pancreatic cancer cells and improved overall survival. Treatment with poly(I:C12U) alone, peptide alone, or gemcitabine alone improved survival in this model system; however, co-administration of poly(I:C12U) and peptide did not provide additive or synergistic benefit in this protocol. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1575. doi:1538-7445.AM2012-1575