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: Research - peer-reviewArticle

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.

LanguageEnglish (US)
Pages237-246
Number of pages10
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Volume14
Issue number2
DOIs
StatePublished - Feb 1 2018

Fingerprint

Immunotherapy
Nanoparticles
Neoplasms
Tumors
poly(beta-amino ester)
Interferons
Esters
Interferon Receptors
Interferon Type I
Experimental Melanomas
Cancer Vaccines
Blocking Antibodies
Tumor Microenvironment
Cytosol
Cytokines
Membranes
Therapeutics
In Vitro Techniques
Vaccines
Antibodies

Keywords

  • Cancer immunotherapy
  • PBAE nanoparticle formulation
  • STING agonist

ASJC Scopus subject areas

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

Cite this

Biodegradable STING agonist nanoparticles for enhanced cancer immunotherapy. / Wilson, David R.; Sen, Rupashree; Sunshine, Joel C.; Pardoll, Drew M.; Green, Jordan J.; Kim, Young J.

In: Nanomedicine: Nanotechnology, Biology, and Medicine, Vol. 14, No. 2, 01.02.2018, p. 237-246.

Research output: Research - peer-reviewArticle

Wilson, David R. ; Sen, Rupashree ; Sunshine, Joel C. ; Pardoll, Drew M. ; Green, Jordan J. ; Kim, Young J./ Biodegradable STING agonist nanoparticles for enhanced cancer immunotherapy. In: Nanomedicine: Nanotechnology, Biology, and Medicine. 2018 ; Vol. 14, No. 2. pp. 237-246
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