Amphiphilic polyanhydride-based recombinant MUC4β-nanovaccine activates dendritic cells
Kasturi Banerjee1,*, Shailendra K Gautam1,*, Prakash Kshirsagar1, Kathleen A Ross3, Gaelle Spagnol1, Paul Sorgen1, Michael J Wannemuehler4,5, Balaji Narasimhan4,5, Joyce C Solheim2,5,6, Sushil Kumar1, Surinder K Batra1,2,5 and Maneesh Jain1,2,5
1 Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA
2 The Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA
3 Department of Chemical and Biological Engineering, Iowa State University, Ames, IA, USA
4 Department of Veterinary Microbiology and Preventive Medicine, Iowa State University, Ames, IA, USA
5 Nanovaccine Institute, Ames, IA and Omaha, NE, USA
6 Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, USA
* These authors contributed equally to the manuscript
Correspondence:
Maneesh Jain, email:
Correspondence:
Sushil Kumar, email:
Keywords: MUC4; pancreatic cancer; cancer vaccine; immunotherapy; nanoparticle
Received: April 24, 2018 Accepted: February 26, 2019 Published: March 14, 2019
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.
