Radiation-enhanced delivery of systemically administered amphiphilic-CpG oligodeoxynucleotide

TitleRadiation-enhanced delivery of systemically administered amphiphilic-CpG oligodeoxynucleotide
Publication TypeJournal Article
Year of Publication2017
AuthorsAppelbe, OK, Moynihan, KD, Flor, A, Rymut, N, Irvine, DJ, Kron, SJ
JournalJournal of Controlled Release
Volume266
Pagination248 - 255
Date Published2017/11/28/
ISBN Number0168-3659
Keywordsbacterial-dna, Cancer therapeutic efficacy, CpG oligodeoxynucleotides, dendritic cells, drug-delivery, Enhanced permeability and retention, established tumors, Immune adjuvant, immune-response, immunostimulatory dna, in-situ vaccination, interferon-gamma, Ionizing radiation, motifs enhance, vascular-permeability
Abstract

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.

Short TitleJ. Control. Release