Campus Units

Chemical and Biological Engineering, Nanovaccine Institute

Document Type

Article

Research Focus Area

Health Care Technology and Biomedical Engineering

Publication Version

Published Version

Publication Date

3-14-2019

Journal or Book Title

Genes and Cancer

DOI

10.18632/genesandcancer.189

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.

Comments

This article is published as Banerjee, Kasturi, Shailendra K. Gautam, Prakash Kshirsagar, Kathleen A. Ross, Gaelle Spagnol, Paul Sorgen, Michael J. Wannemuehler, Balaji Narasimhan, Joyce C. Solheim, Sushil Kumar, Surinder K. Batra, and Maneesh Jain. "Amphiphilic polyanhydride-based recombinant MUC4β-nanovaccine activates dendritic cells." Genes & Cancer (2019). DOI: 10.18632/genesandcancer.189. Posted with permission.

Creative Commons License

Creative Commons Attribution 3.0 License
This work is licensed under a Creative Commons Attribution 3.0 License.

Copyright Owner

Banerjee et al.

Language

en

File Format

application/pdf

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