Immune modulatory nanoparticle therapeutics for intracerebral glioma

Nasser K. Yaghi, Jun Wei, Yuuri Hashimoto, Ling Yuan Kong, Konrad Gabrusiewicz, Edjah K. Nduom, Xiaoyang Ling, Neal Huang, Shouhao Zhou, Brittany C.Parker Kerrigan, Jonathan M. Levine, Virginia R. Fajt, Gwendolyn Levine, Brian F. Porter, Eric G. Marcusson, Kiyoshi Tachikawa, Padmanabh Chivukula, David C. Webb, Joseph E. Payne, Amy B. Heimberger

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Background: Previously we showed therapeutic efficacy of unprotected miR-124 in preclinical murine models of glioblastoma, including in heterogeneous genetically engineered murine models by exploiting the immune system and thereby negating the need for direct tumor delivery. Although these data were promising, to implement clinical trials, we required a scalable formulation that afforded protection against circulatory RNases. Methods: We devised lipid nanoparticles that encapsulate and protect the miRs from degradation and provide enhanced delivery into the immune cell compartment and tested in vivo antitumor effects. Results: Treatment with nanoparticle-encapsulated miR-124, LUNAR-301, demonstrated a median survival exceeding 70 days, with an associated reversal of tumor-mediated immunosuppression and induction of immune memory. In both canine and murine models, the safety profile of LUNAR-301 was favorable. Conclusions: For the first time, we show that nanoparticles can direct a therapeutic response by targeting intracellular immune pathways. Although shown in the context of gliomas, this therapeutic approach would be applicable to other malignancies.

Original languageEnglish (US)
Pages (from-to)372-382
Number of pages11
JournalNeuro-oncology
Volume19
Issue number3
DOIs
StatePublished - Mar 1 2017

All Science Journal Classification (ASJC) codes

  • Oncology
  • Clinical Neurology
  • Cancer Research

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