title: Immune modulatory nanoparticle therapeutics for intracerebral glioma.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Departments of Neurosurgery, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Nasser K
authors.initials: NK
authors.lastname: Yaghi
authors.affiliation: Departments of Neurosurgery, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Wei
authors.affiliation: Departments of Neurosurgery, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Yuuri
authors.initials: Y
authors.lastname: Hashimoto
authors.affiliation: Departments of Neurosurgery, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Ling-Yuan
authors.initials: LY
authors.lastname: Kong
authors.affiliation: Departments of Neurosurgery, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Konrad
authors.initials: K
authors.lastname: Gabrusiewicz
authors.affiliation: Departments of Neurosurgery, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Edjah K
authors.initials: EK
authors.lastname: Nduom
authors.affiliation: Departments of Neurosurgery, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Ling
authors.affiliation: Departments of Neurosurgery, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Neal
authors.initials: N
authors.lastname: Huang
authors.affiliation: Biostatistics, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Shouhao
authors.initials: S
authors.lastname: Zhou
authors.affiliation: Departments of Neurosurgery, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Brittany C Parker
authors.initials: BC
authors.lastname: Kerrigan
authors.affiliation: Texas A&M University College of Veterinary Medicine & Biomedical Sciences, College Station, Texas, USA.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Levine
authors.affiliation: Texas A&M University College of Veterinary Medicine & Biomedical Sciences, College Station, Texas, USA.
authors.forename: Virginia R
authors.initials: VR
authors.lastname: Fajt
authors.affiliation: Texas A&M University College of Veterinary Medicine & Biomedical Sciences, College Station, Texas, USA.
authors.forename: Gwendolyn
authors.initials: G
authors.lastname: Levine
authors.affiliation: Texas A&M University College of Veterinary Medicine & Biomedical Sciences, College Station, Texas, USA.
authors.forename: Brian F
authors.initials: BF
authors.lastname: Porter
authors.affiliation: Arcturus Therapeutics, San Diego, California, USA.
authors.forename: Eric G
authors.initials: EG
authors.lastname: Marcusson
authors.affiliation: Arcturus Therapeutics, San Diego, California, USA.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Tachikawa
authors.affiliation: Arcturus Therapeutics, San Diego, California, USA.
authors.forename: Padmanabh
authors.initials: P
authors.lastname: Chivukula
authors.affiliation: Arcturus Therapeutics, San Diego, California, USA.
authors.forename: David C
authors.initials: DC
authors.lastname: Webb
authors.affiliation: Arcturus Therapeutics, San Diego, California, USA.
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Payne
authors.affiliation: Departments of Neurosurgery, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Amy B
authors.initials: AB
authors.lastname: Heimberger
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D004285:Dogs; D005910:Glioma / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D006801:Humans; D007108:Immune Tolerance / Q000235:genetics*; D007156:Immunologic Memory / Q000235:genetics; D008055:Lipids / Q000737:chemistry*; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000008:administration & dosage / Q000235:genetics*; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D008055:Lipids; D035683:MicroRNAs; C540079:Mirn124 microRNA, mouse
keywords: glioma; immunotherapy; microRNAs; nanoparticles; STAT3