{
  "abstract": "Malignant glioma is considered invariably recalcitrant, thus necessitating development of new therapeutic approaches. Spontaneously arising canine glioma exhibits important molecular and pathological similarities to malignant pediatric glioma, making it an invaluable model for testing novel therapies. We evaluated safety and activity of RNA lipid particle aggregates (LPAs) designed to provoke cancer immunogenicity in 10 dogs with histologically confirmed glioma. Vaccine manufacturing was feasible in all subjects and generally well tolerated. Median survival time was 123 and 155 days in dogs receiving three (Group A) or four (Group B) vaccines, respectively; this was increased from historical reporting of subjects receiving palliative care. Responding animals had a robust cytokine response following infusions. In animals receiving non-specific RNA-LPAs, there was localization of messenger RNA (mRNA) payloads to the brain tumor microenvironment and a rapid shift in immunologic gene signatures consistent with a viral response. These data demonstrate the ability to induce rapid viremic response in the tumor microenvironment following a single peripherally administered mRNA vaccine. Since RNA-LPAs are amenable to repeat boosts, these formulations may overcome challenges of tumor immunosuppression and therapeutic access and are currently under evaluation in first-in-human trials (NCT04573140, NCT06389591).",
  "authors": [
    {
      "affiliations": [
        "Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, Florida, USA"
      ],
      "name": "Sheila Carrera-Justiz"
    },
    {
      "affiliations": [
        "Laboratory for Systems Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, College of Medicine, University of Florida, Gainesville, Florida, USA"
      ],
      "name": "Mahya Aghaee"
    },
    {
      "affiliations": [
        "University of Florida Genetics Institute, Gainesville, Florida, USA",
        "Preston A. Wells, Jr. Center for Brain Tumor Therapy, McKnight Brain Institute, Lillian S. Wells Department of Neurosurgery, College of Medicine, University of Florida, Gainesville, Florida, USA"
      ],
      "name": "Sadeem Qdaisat"
    },
    {
      "affiliations": [
        "Preston A. Wells, Jr. Center for Brain Tumor Therapy, McKnight Brain Institute, Lillian S. Wells Department of Neurosurgery, College of Medicine, University of Florida, Gainesville, Florida, USA"
      ],
      "name": "Frances Weidert"
    },
    {
      "affiliations": [
        "Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, Florida, USA"
      ],
      "name": "Gabriel A Garcia"
    },
    {
      "affiliations": [
        "Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, Florida, USA"
      ],
      "name": "Lana Fagman"
    },
    {
      "affiliations": [
        "Preston A. Wells, Jr. Center for Brain Tumor Therapy, McKnight Brain Institute, Lillian S. Wells Department of Neurosurgery, College of Medicine, University of Florida, Gainesville, Florida, USA"
      ],
      "name": "Dingpeng Zhang"
    },
    {
      "affiliations": [
        "Department of Pediatrics, College of Medicine, University of Florida, Gainesville, Florida, USA"
      ],
      "name": "Brian Stover"
    },
    {
      "affiliations": [
        "Preston A. Wells, Jr. Center for Brain Tumor Therapy, McKnight Brain Institute, Lillian S. Wells Department of Neurosurgery, College of Medicine, University of Florida, Gainesville, Florida, USA"
      ],
      "name": "Rachel S F Moor"
    },
    {
      "affiliations": [
        "Preston A. Wells, Jr. Center for Brain Tumor Therapy, McKnight Brain Institute, Lillian S. Wells Department of Neurosurgery, College of Medicine, University of Florida, Gainesville, Florida, USA"
      ],
      "name": "Chao Xie"
    },
    {
      "affiliations": [
        "Preston A. Wells, Jr. Center for Brain Tumor Therapy, McKnight Brain Institute, Lillian S. Wells Department of Neurosurgery, College of Medicine, University of Florida, Gainesville, Florida, USA"
      ],
      "name": "Eden Goldenberg"
    },
    {
      "affiliations": [
        "Preston A. Wells, Jr. Center for Brain Tumor Therapy, McKnight Brain Institute, Lillian S. Wells Department of Neurosurgery, College of Medicine, University of Florida, Gainesville, Florida, USA"
      ],
      "name": "Christina von Roemeling"
    },
    {
      "affiliations": [
        "Department of Medicine, Division of Hematology-Oncology, UF Health Cancer Center, College of Medicine, University of Florida, Gainesville, Florida, USA"
      ],
      "name": "Bently Doonan"
    },
    {
      "affiliations": [
        "Preston A. Wells, Jr. Center for Brain Tumor Therapy, McKnight Brain Institute, Lillian S. Wells Department of Neurosurgery, College of Medicine, University of Florida, Gainesville, Florida, USA"
      ],
      "name": "Jonathan Chardon-Robles"
    },
    {
      "affiliations": [
        "Department of Medicine, Division of Hematology-Oncology, UF Health Cancer Center, College of Medicine, University of Florida, Gainesville, Florida, USA"
      ],
      "name": "Leighton Elliott"
    },
    {
      "affiliations": [
        "Moffitt Cancer Center, Tampa, Florida, USA"
      ],
      "name": "W Gregory Sawyer"
    },
    {
      "affiliations": [
        "Department of Molecular Medicine, Mayo Clinic, Jacksonville, Florida, USA"
      ],
      "name": "Loic P Deleyrolle"
    },
    {
      "affiliations": [
        "Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, Florida, USA"
      ],
      "name": "Bikash Sahay"
    },
    {
      "affiliations": [
        "Department of Pediatrics, College of Medicine, University of Florida, Gainesville, Florida, USA"
      ],
      "name": "Timothy P Foster"
    },
    {
      "affiliations": [
        "Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, Gainesville, Florida, USA"
      ],
      "name": "Nathan D Seligson"
    },
    {
      "affiliations": [
        "Preston A. Wells, Jr. Center for Brain Tumor Therapy, McKnight Brain Institute, Lillian S. Wells Department of Neurosurgery, College of Medicine, University of Florida, Gainesville, Florida, USA"
      ],
      "name": "Maryam Rahman"
    },
    {
      "affiliations": [
        "Preston A. Wells, Jr. Center for Brain Tumor Therapy, McKnight Brain Institute, Lillian S. Wells Department of Neurosurgery, College of Medicine, University of Florida, Gainesville, Florida, USA"
      ],
      "name": "Ashley Ghiaseddin"
    },
    {
      "affiliations": [
        "Department of Pediatrics, College of Medicine, University of Florida, Gainesville, Florida, USA"
      ],
      "name": "Paul Castillo"
    },
    {
      "affiliations": [
        "Department of Biostatistics, University of Florida, Gainesville, Florida, USA"
      ],
      "name": "Ji-Hyun Lee"
    },
    {
      "affiliations": [
        "Cleveland Clinic Head and Neck Institute and Center of Immunotherapy and Precision Immuno-Oncology, Cleveland Clinic Lerner College of Medicine, Cleveland Clinic, Cleveland, Ohio, USA"
      ],
      "name": "Natalie L Silver"
    },
    {
      "affiliations": [
        "Preston A. Wells, Jr. Center for Brain Tumor Therapy, McKnight Brain Institute, Lillian S. Wells Department of Neurosurgery, College of Medicine, University of Florida, Gainesville, Florida, USA"
      ],
      "name": "Andria Doty"
    },
    {
      "affiliations": [
        "Department of Pediatrics, College of Medicine, University of Florida, Gainesville, Florida, USA"
      ],
      "name": "John A Ligon"
    },
    {
      "affiliations": [
        "Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, Florida, USA"
      ],
      "name": "Rowan J Milner"
    },
    {
      "affiliations": [
        "Preston A. Wells, Jr. Center for Brain Tumor Therapy, McKnight Brain Institute, Lillian S. Wells Department of Neurosurgery, College of Medicine, University of Florida, Gainesville, Florida, USA"
      ],
      "name": "Duane Mitchell"
    },
    {
      "affiliations": [
        "Preston A. Wells, Jr. Center for Brain Tumor Therapy, McKnight Brain Institute, Lillian S. Wells Department of Neurosurgery, College of Medicine, University of Florida, Gainesville, Florida, USA"
      ],
      "name": "Hector Mendez-Gomez"
    },
    {
      "affiliations": [
        "Laboratory for Systems Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, College of Medicine, University of Florida, Gainesville, Florida, USA"
      ],
      "name": "Helen Moore"
    },
    {
      "affiliations": [
        "Preston A. Wells, Jr. Center for Brain Tumor Therapy, McKnight Brain Institute, Lillian S. Wells Department of Neurosurgery, College of Medicine, University of Florida, Gainesville, Florida, USA"
      ],
      "name": "Elias J Sayour"
    }
  ],
  "title": "Systemic mRNA vaccines elicit rapid immune activation in canine brain tumors",
  "uid": "cb596294-4474-5d74-9920-80c418bbe735"
}