Inhibition of lung metastasis by chemokine CCL17-mediated in vivo silencing of genes in CCR4+ Tregs

Arya Biragyn*, Monica Bodogai, Purevdorj B. Olkhanud, Sinan R. Denny-Brown, Nitin Puri, Koichi Ayukawa, Shiro Kanegasaki, Cory M. Hogaboam, Katarzyna Wejksza, Catalina Lee Chang

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Despite significant attractiveness of antisense oligonucleotide/RNAi technology, its clinical application has been precluded by a lack of methods for targeted delivery and transduction of primary immune cells in vivo. Here, we devised a chemokine CCL17-based strategy (TARC-arp) that transiently silences expression of genes in immune cells by delivering inhibitory oligonucleotides through their chemokine receptors. In modeling studies using mice with established 4T1.2 breast cancer, we show that IL10 produced by CCR4 cells, in particular FoxP3 regulatory T cells (Tregs), plays an important role in lung metastasis. As such, TARC-arp-mediated silencing of IL10 or FoxP3 in CCR4 Tregs is sufficient to block lung metastasis. Thus, we provide a simple solution that circumvents the problems of RNAi use in vivo, indicating that a disease outcome can be successfully controlled by delivering inhibitory oligonucleotides with chemokines to inactivate a selective subset of immune cells.

Original languageEnglish (US)
Pages (from-to)258-267
Number of pages10
JournalJournal of Immunotherapy
Volume36
Issue number4
DOIs
StatePublished - May 2013

Keywords

  • FoxP3
  • IL10
  • Tregs
  • chemokine
  • metastasis
  • siRNA delivery

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology
  • Cancer Research

Fingerprint Dive into the research topics of 'Inhibition of lung metastasis by chemokine CCL17-mediated in vivo silencing of genes in CCR4+ Tregs'. Together they form a unique fingerprint.

Cite this