Ontology highlight
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.
SUBMITTER: Yaghi NK
PROVIDER: S-EPMC5464307 | biostudies-literature | 2017 Mar
REPOSITORIES: biostudies-literature
Yaghi Nasser K NK Wei Jun J Hashimoto Yuuri Y Kong Ling-Yuan LY Gabrusiewicz Konrad K Nduom Edjah K EK Ling Xiaoyang X Huang Neal N Zhou Shouhao S Kerrigan Brittany C Parker BC Levine Jonathan M JM Fajt Virginia R VR Levine Gwendolyn G Porter Brian F BF Marcusson Eric G EG Tachikawa Kiyoshi K Chivukula Padmanabh P Webb David C DC Payne Joseph E JE Heimberger Amy B AB
Neuro-oncology 20170301 3
<h4>Background</h4>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.<h4>Methods</h4>We devised lipid nanoparticles that encapsulate ...[more]