Biodegradable STING agonist nanoparticles for enhanced cancer immunotherapy

David R. Wilson, Rupashree Sen, Joel C. Sunshine, Drew M. Pardoll, Jordan J. Green, Young J. Kim

Research output: Contribution to journalArticle

Abstract

Therapeutic cancer vaccines require adjuvants leading to robust type I interferon and proinflammatory cytokine responses in the tumor microenvironment to induce an anti-tumor response. Cyclic dinucleotides (CDNs), a potent Stimulator of Interferon Receptor (STING) agonist, are currently in phase I trials. However, their efficacy may be limited to micromolar concentrations due to the cytosolic residence of STING in the ER membrane. Here we utilized biodegradable, poly(beta-amino ester) (PBAE) nanoparticles to deliver CDNs to the cytosol leading to robust immune response at >100-fold lower extracellular CDN concentrations in vitro. The leading CDN PBAE nanoparticle formulation induced a log-fold improvement in potency in treating established B16 melanoma tumors in vivo when combined with PD-1 blocking antibody in comparison to free CDN without nanoparticles. This nanoparticle-mediated cytosolic delivery method for STING agonists synergizes with checkpoint inhibitors and has strong potential for enhanced cancer immunotherapy.

Original languageEnglish (US)
Pages (from-to)237-246
Number of pages10
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Volume14
Issue number2
DOIs
StatePublished - Feb 2018

Keywords

  • Cancer immunotherapy
  • PBAE nanoparticle formulation
  • STING agonist

ASJC Scopus subject areas

  • Bioengineering
  • Medicine (miscellaneous)
  • Molecular Medicine
  • Biomedical Engineering
  • Materials Science(all)
  • Pharmaceutical Science

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