Nanoparticle-mediated tumor cell expression of mIL-12 via systemic gene delivery treats syngeneic models of murine lung cancers

Hye Hyun Ahn, Christine Carrington, Yizong Hu, Heng wen Liu, Christy Ng, Hwanhee Nam, Andrew Park, Catherine Stace, Will West, Hai Quan Mao, Martin G. Pomper, Christopher G. Ullman, Il Minn

Research output: Contribution to journalArticlepeer-review

Abstract

Treatment of cancers in the lung remains a critical challenge in the clinic for which gene therapy could offer valuable options. We describe an effective approach through systemic injection of engineered polymer/DNA nanoparticles that mediate tumor-specific expression of a therapeutic gene, under the control of the cancer-selective progression elevated gene 3 (PEG-3) promoter, to treat tumors in the lungs of diseased mice. A clinically tested, untargeted, polyethylenimine carrier was selected to aid rapid transition to clinical studies, and a CpG-free plasmid backbone and coding sequences were used to reduce inflammation. Intravenous administration of nanoparticles expressing murine single-chain interleukin 12, under the control of PEG-3 promoter, significantly improved the survival of mice in both an orthotopic and a metastatic model of lung cancer with no marked symptoms of systemic toxicity. These outcomes achieved using clinically relevant nanoparticle components raises the promise of translation to human therapy.

Original languageEnglish (US)
Article number9733
JournalScientific reports
Volume11
Issue number1
DOIs
StatePublished - Dec 2021

ASJC Scopus subject areas

  • General

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