Radiation-enhanced delivery of systemically administered amphiphilic-CpG oligodeoxynucleotide
Author(s)
Appelbe, Oliver K.; Flor, Amy; Rymut, Nick; Kron, Stephen J.; Moynihan, Kelly Dare; Irvine, Darrell J; ... Show more Show less
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Along with vaccines and checkpoint blockade, immune adjuvants may have an important role in tumor immunotherapy. Oligodeoxynucleotides containing unmethylated cytidyl guanosyl dinucleotide motifs (CpG ODN) are TLR9 ligands with attractive immunostimulatory properties, but intratumoral administration has been required to induce an effective anti-tumor immune response. Following on recent studies with radiation-targeted delivery of nanoparticles, we examined enhanced tumor-specific delivery of amphiphile-CpG, an albumin-binding analog of CpG ODN, following systemic administration 3 days after tumor irradiation. The combination of radiation and CpG displayed superior tumor control over either treatment alone. Intravital imaging of fluorescently labeled amphiphilic-CpG revealed increased accumulation in irradiated tumors along with decreased off-target accumulation in visceral organs. Within 48 h after amphiphile-CpG administration, immune activation could be detected by increased Granzyme B and Interferon gamma activity in the tumor as well as in circulating monocytes and activated CD8+T cells. Using radiotherapy to enhance the targeting of CpG to tumors may help advance this once promising therapy to clinical relevance. Keywords: CpG oligodeoxynucleotides; Ionizing radiation; Immune adjuvant; Enhanced permeability and retention; Cancer therapeutic efficacy
Date issued
2017-10Department
Massachusetts Institute of Technology. Department of Biological Engineering; Massachusetts Institute of Technology. Department of Materials Science and Engineering; Koch Institute for Integrative Cancer Research at MITJournal
Journal of Controlled Release
Publisher
Elsevier
Citation
Appelbe, Oliver K. et al. “Radiation-Enhanced Delivery of Systemically Administered Amphiphilic-CpG Oligodeoxynucleotide.” Journal of Controlled Release 266 (November 2017): 248–255 © 2017 Elsevier B.V.
Version: Author's final manuscript
ISSN
0168-3659