Amphiphilic polyanhydride-based recombinant MUC4β-nanovaccine activates dendritic cells

Kasturi Banerjee, Shailendra K. Gautam, Prakash Kshirsagar, Kathleen A. Ross, Gaelle Spagnol, Paul L Sorgen, Michael J. Wannemuehler, Balaji Narasimhan, Joyce C Solheim, Sushil Kumar, Surinder Kumar Batra, Maneesh Jain

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)52-62
Number of pages11
JournalGenes and Cancer
Volume10
Issue number3-4
DOIs
StatePublished - Jan 1 2019

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Mucin-4
Polyanhydrides
Dendritic Cells
Nanoparticles
Pancreatic Neoplasms
Immunotherapy
Immunoglobulin Class Switching
Adaptive Immunity
Interleukin-12

Keywords

  • Cancer vaccine
  • Immunotherapy
  • MUC4
  • Nanoparticle
  • Pancreatic cancer

ASJC Scopus subject areas

  • Genetics
  • Cancer Research

Cite this

Amphiphilic polyanhydride-based recombinant MUC4β-nanovaccine activates dendritic cells. / Banerjee, Kasturi; Gautam, Shailendra K.; Kshirsagar, Prakash; Ross, Kathleen A.; Spagnol, Gaelle; Sorgen, Paul L; Wannemuehler, Michael J.; Narasimhan, Balaji; Solheim, Joyce C; Kumar, Sushil; Batra, Surinder Kumar; Jain, Maneesh.

In: Genes and Cancer, Vol. 10, No. 3-4, 01.01.2019, p. 52-62.

Research output: Contribution to journalArticle

Banerjee, K, Gautam, SK, Kshirsagar, P, Ross, KA, Spagnol, G, Sorgen, PL, Wannemuehler, MJ, Narasimhan, B, Solheim, JC, Kumar, S, Batra, SK & Jain, M 2019, 'Amphiphilic polyanhydride-based recombinant MUC4β-nanovaccine activates dendritic cells', Genes and Cancer, vol. 10, no. 3-4, pp. 52-62. https://doi.org/10.18632/oncoscience.189
Banerjee, Kasturi ; Gautam, Shailendra K. ; Kshirsagar, Prakash ; Ross, Kathleen A. ; Spagnol, Gaelle ; Sorgen, Paul L ; Wannemuehler, Michael J. ; Narasimhan, Balaji ; Solheim, Joyce C ; Kumar, Sushil ; Batra, Surinder Kumar ; Jain, Maneesh. / Amphiphilic polyanhydride-based recombinant MUC4β-nanovaccine activates dendritic cells. In: Genes and Cancer. 2019 ; Vol. 10, No. 3-4. pp. 52-62.
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