Year: 2019
Type: article
Abstract: Mucin 4 (MUC4) is a high molecular weight glycoprotein that is differentially overexpressed in pancreatic cancer (PC), functionally contributes to disease progression, and correlates with poor survival. Further, due to its aberrant glycosylation and extensive splicing, MUC4 is a potential target for cancer immunotherapy. Our previous studies have demonstrated the utility of amphiphilic polyanhydride nanoparticles as a useful platform for the development of protein-based prophylactic and therapeutic vaccines. In the present study, we encapsulated purified recombinant human MUC4-beta (MUC4β) protein in polyanhydride (20:80 CPTEG:CPH) nanoparticles (MUC4β-nanovaccine) and evaluated its ability to activate dendritic cells and induce adaptive immunity. Immature dendritic cells when pulsed with MUC4β-nanovaccine exhibited significant increase in the surface expressions of MHC I and MHC II and costimulatory molecules (CD80 and CD86), as well as, secretion of pro-inflammatory cytokines (IFN-γ, IL-6, and IL-12) as compared to cells exposed to MUC4β alone or MUC4β mixed with blank nanoparticles (MUC4β+NP). Following immunization, as compared to the other formulations, MUC4β-nanovaccine elicited higher IgG2b to IgG1 ratio of anti-MUC4β-antibodies suggesting a predominantly Th1-like class switching. Thus, our findings demonstrate MUC4β-nanovaccine as a novel platform for PC immunotherapy.
Source: Genes & Cancer
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: diamond
Awards: New Strategy for Pancreatic Cancer Therapy, Targeting Mucin and EGFR Axis in Pancreatic Cancer, G2034580661, G226765565, Alcohol and smoking concurrently aggravate chronic pancreatitis, G269183255, G281700398, Smoking and pancreatic cancer, G4569525196, G5989231044, SPORE in Pancreatic Cancer, Nanovaccine platforms to combat pancreatic cancer, Targeted Radiation Therapy for Pancreatic Cancer, Buffett Cancer Center Support Grant, Validation of biomarkers for risk prediction and early diagnosis of Pancreatic Adenocarcinoma
OpenAlex ID: W2922774803