Polyanhydride based nanovaccine promotes long term humoral and cellular response to PDAC associated protein MUC4β

Abstract

Abstract Patients diagnosed with pancreatic ductal adenocarcinoma (PDAC) have an unrelentingly poor prognosis, in part because of the lack of neoantigen targets associated with PDAC tumors. However, another approach would be to take advantage of differentially expressed antigens on PDAC tumor cells. It has been demonstrated that mucin 4 (MUC4) is overexpressed on the tumor cells of many PDAC patients and is considered a promising antigenic target for PC immunotherapy. Previous work by our lab has demonstrated that poly-anhydride (PA) nanovaccines based on 20:80 1,8-bis(p-carboxyphenoxy)-3,6-dioxaoctane (CPTEG) and 1,6-bis(p-carboxyphenoxy)hexane (CPH) nanoparticles (NPs) both induced a humoral immune response to the beta subunit of MUC4 (MUC4β) and an anti-tumor response against OVA in an EG-7 tumor model. In these studies, we show that both a PA-based nanovaccine formulation and a PLGA-based nanovaccine induced MUC4β-specific T cell response. Results demonstrated that restimulation of LN and splenic lymphocytes 40 days after initial vaccination induced both CD4+ and CD8+ MUC4β-specific T cells. The MUC4ß-specific T cells could be detected for at least 180 days post-vaccination. Cytokine secretions from the antigen specific T cells included IL-2, INFγ, and TNF-α; in addition, tetramer analysis detected MUC4ß-specific CD8+ T cells using the MUCβ peptide FTPVFYSQL. Collectively, these results demonstrate that a PA nanovaccine can function as an effective vaccine platform for induction of MUC4ß-specific cellular immunity, and lays the ground work for forthcoming studies in MUC4β-expressing tumor model systems. Supported by the National Institute of Health (U01 CA213862) and the Iowa State University Nanovaccine Institute. B. N. is grateful to the Vlasta Klima Balloun Faculty Chair.