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RNA aggregates harness the danger response for potent cancer immunotherapy.
Mendez-Gomez, Hector R; DeVries, Anna; Castillo, Paul; von Roemeling, Christina; Qdaisat, Sadeem; Stover, Brian D; Xie, Chao; Weidert, Frances; Zhao, Chong; Moor, Rachel; Liu, Ruixuan; Soni, Dhruvkumar; Ogando-Rivas, Elizabeth; Chardon-Robles, Jonathan; McGuiness, James; Zhang, Dingpeng; Chung, Michael C; Marconi, Christiano; Michel, Stephen; Barpujari, Arnav; Jobin, Gabriel W; Thomas, Nagheme; Ma, Xiaojie; Campaneria, Yodarlynis; Grippin, Adam; Karachi, Aida; Li, Derek; Sahay, Bikash; Elliott, Leighton; Foster, Timothy P; Coleman, Kirsten E; Milner, Rowan J; Sawyer, W Gregory; Ligon, John A; Simon, Eugenio; Cleaver, Brian; Wynne, Kristine; Hodik, Marcia; Molinaro, Annette M; Guan, Juan; Kellish, Patrick; Doty, Andria; Lee, Ji-Hyun; Massini, Tara; Kresak, Jesse L; Huang, Jianping; Hwang, Eugene I; Kline, Cassie; Carrera-Justiz, Sheila; Rahman, Maryam.
Affiliation
  • Mendez-Gomez HR; University of Florida Lillian S. Wells Department of Neurosurgery, Preston A. Wells, Jr. Center for Brain Tumor Therapy, Gainesville, FL 32610, USA.
  • DeVries A; University of Florida Lillian S. Wells Department of Neurosurgery, Preston A. Wells, Jr. Center for Brain Tumor Therapy, Gainesville, FL 32610, USA.
  • Castillo P; University of Florida, Department of Pediatrics, Division of Hematology-Oncology, Gainesville, FL 32610, USA.
  • von Roemeling C; University of Florida Lillian S. Wells Department of Neurosurgery, Preston A. Wells, Jr. Center for Brain Tumor Therapy, Gainesville, FL 32610, USA.
  • Qdaisat S; University of Florida Lillian S. Wells Department of Neurosurgery, Preston A. Wells, Jr. Center for Brain Tumor Therapy, Gainesville, FL 32610, USA; University of Florida Genetics Institute, Gainesville, FL 32610, USA.
  • Stover BD; University of Florida, Department of Pediatrics, Division of Hematology-Oncology, Gainesville, FL 32610, USA.
  • Xie C; University of Florida Lillian S. Wells Department of Neurosurgery, Preston A. Wells, Jr. Center for Brain Tumor Therapy, Gainesville, FL 32610, USA.
  • Weidert F; University of Florida Lillian S. Wells Department of Neurosurgery, Preston A. Wells, Jr. Center for Brain Tumor Therapy, Gainesville, FL 32610, USA.
  • Zhao C; University of Florida Lillian S. Wells Department of Neurosurgery, Preston A. Wells, Jr. Center for Brain Tumor Therapy, Gainesville, FL 32610, USA.
  • Moor R; University of Florida Lillian S. Wells Department of Neurosurgery, Preston A. Wells, Jr. Center for Brain Tumor Therapy, Gainesville, FL 32610, USA.
  • Liu R; University of Florida Lillian S. Wells Department of Neurosurgery, Preston A. Wells, Jr. Center for Brain Tumor Therapy, Gainesville, FL 32610, USA.
  • Soni D; University of Florida Lillian S. Wells Department of Neurosurgery, Preston A. Wells, Jr. Center for Brain Tumor Therapy, Gainesville, FL 32610, USA.
  • Ogando-Rivas E; University of Florida Lillian S. Wells Department of Neurosurgery, Preston A. Wells, Jr. Center for Brain Tumor Therapy, Gainesville, FL 32610, USA.
  • Chardon-Robles J; University of Florida Lillian S. Wells Department of Neurosurgery, Preston A. Wells, Jr. Center for Brain Tumor Therapy, Gainesville, FL 32610, USA.
  • McGuiness J; University of Florida Lillian S. Wells Department of Neurosurgery, Preston A. Wells, Jr. Center for Brain Tumor Therapy, Gainesville, FL 32610, USA.
  • Zhang D; University of Florida Lillian S. Wells Department of Neurosurgery, Preston A. Wells, Jr. Center for Brain Tumor Therapy, Gainesville, FL 32610, USA.
  • Chung MC; University of Texas at Austin, College of Pharmacy, Division of Chemical Biology and Medicinal Chemistry, Austin TX 78712.
  • Marconi C; University of Florida Lillian S. Wells Department of Neurosurgery, Preston A. Wells, Jr. Center for Brain Tumor Therapy, Gainesville, FL 32610, USA.
  • Michel S; University of Florida Lillian S. Wells Department of Neurosurgery, Preston A. Wells, Jr. Center for Brain Tumor Therapy, Gainesville, FL 32610, USA.
  • Barpujari A; University of Florida, Department of Pediatrics, Division of Hematology-Oncology, Gainesville, FL 32610, USA.
  • Jobin GW; University of Florida, Department of Pediatrics, Division of Hematology-Oncology, Gainesville, FL 32610, USA.
  • Thomas N; University of Florida Lillian S. Wells Department of Neurosurgery, Preston A. Wells, Jr. Center for Brain Tumor Therapy, Gainesville, FL 32610, USA.
  • Ma X; University of Florida Lillian S. Wells Department of Neurosurgery, Preston A. Wells, Jr. Center for Brain Tumor Therapy, Gainesville, FL 32610, USA; University of Florida, Department of Pediatrics, Division of Hematology-Oncology, Gainesville, FL 32610, USA.
  • Campaneria Y; University of Florida Lillian S. Wells Department of Neurosurgery, Preston A. Wells, Jr. Center for Brain Tumor Therapy, Gainesville, FL 32610, USA.
  • Grippin A; University of Florida Lillian S. Wells Department of Neurosurgery, Preston A. Wells, Jr. Center for Brain Tumor Therapy, Gainesville, FL 32610, USA.
  • Karachi A; University of Florida Lillian S. Wells Department of Neurosurgery, Preston A. Wells, Jr. Center for Brain Tumor Therapy, Gainesville, FL 32610, USA.
  • Li D; University of Florida, Division of Quantitative Sciences, UF Health Cancer Center, Gainesville, FL 32610, USA.
  • Sahay B; University of Florida, College of Veterinary Medicine, Gainesville, FL 32610, USA.
  • Elliott L; University of Florida, Department of Medicine, Division of Hematology-Oncology, Gainesville, FL 32610, USA.
  • Foster TP; University of Florida, Department of Pediatrics, Division of Hematology-Oncology, Gainesville, FL 32610, USA.
  • Coleman KE; University of Florida, Department of Pediatrics, Division of Hematology-Oncology, Gainesville, FL 32610, USA.
  • Milner RJ; University of Florida, College of Veterinary Medicine, Gainesville, FL 32610, USA.
  • Sawyer WG; H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 33612, USA.
  • Ligon JA; University of Florida, Department of Pediatrics, Division of Hematology-Oncology, Gainesville, FL 32610, USA.
  • Simon E; University of Florida Lillian S. Wells Department of Neurosurgery, Preston A. Wells, Jr. Center for Brain Tumor Therapy, Gainesville, FL 32610, USA.
  • Cleaver B; University of Florida Lillian S. Wells Department of Neurosurgery, Preston A. Wells, Jr. Center for Brain Tumor Therapy, Gainesville, FL 32610, USA.
  • Wynne K; University of Florida Lillian S. Wells Department of Neurosurgery, Preston A. Wells, Jr. Center for Brain Tumor Therapy, Gainesville, FL 32610, USA.
  • Hodik M; University of Florida Lillian S. Wells Department of Neurosurgery, Preston A. Wells, Jr. Center for Brain Tumor Therapy, Gainesville, FL 32610, USA.
  • Molinaro AM; University of California, San Francisco, Department of Neurological Surgery, San Francisco, CA 94158, USA.
  • Guan J; University of Texas at Austin, College of Pharmacy, Division of Chemical Biology and Medicinal Chemistry, Austin TX 78712.
  • Kellish P; University of Florida Interdisciplinary Center for Biotechnology Research, Gainesville, FL 32610, USA.
  • Doty A; University of Florida Interdisciplinary Center for Biotechnology Research, Gainesville, FL 32610, USA.
  • Lee JH; University of Florida, Department of Biostatistics, Gainesville, FL 32610, USA.
  • Massini T; University of Florida, Department of Radiology, Gainesville, FL 32610, USA.
  • Kresak JL; University of Florida, Department of Pathology, Gainesville, FL 32610, USA.
  • Huang J; University of Florida Lillian S. Wells Department of Neurosurgery, Preston A. Wells, Jr. Center for Brain Tumor Therapy, Gainesville, FL 32610, USA.
  • Hwang EI; Children's National Hospital, Center for Cancer and Blood Disorders, Washington, DC 20010, USA.
  • Kline C; University of Pennsylvania Perelman School of Medicine, Children's Hospital of Philadelphia, Department of Pediatrics, Division of Oncology, Philadelphia, PA 19104, USA.
  • Carrera-Justiz S; University of Florida, College of Veterinary Medicine, Gainesville, FL 32610, USA.
  • Rahman M; University of Florida Lillian S. Wells Department of Neurosurgery, Preston A. Wells, Jr. Center for Brain Tumor Therapy, Gainesville, FL 32610, USA.
Cell ; 187(10): 2521-2535.e21, 2024 May 09.
Article in En | MEDLINE | ID: mdl-38697107
ABSTRACT
Cancer immunotherapy remains limited by poor antigenicity and a regulatory tumor microenvironment (TME). Here, we create "onion-like" multi-lamellar RNA lipid particle aggregates (LPAs) to substantially enhance the payload packaging and immunogenicity of tumor mRNA antigens. Unlike current mRNA vaccine designs that rely on payload packaging into nanoparticle cores for Toll-like receptor engagement in immune cells, systemically administered RNA-LPAs activate RIG-I in stromal cells, eliciting massive cytokine/chemokine response and dendritic cell/lymphocyte trafficking that provokes cancer immunogenicity and mediates rejection of both early- and late-stage murine tumor models. In client-owned canines with terminal gliomas, RNA-LPAs improved survivorship and reprogrammed the TME, which became "hot" within days of a single infusion. In a first-in-human trial, RNA-LPAs elicited rapid cytokine/chemokine release, immune activation/trafficking, tissue-confirmed pseudoprogression, and glioma-specific immune responses in glioblastoma patients. These data support RNA-LPAs as a new technology that simultaneously reprograms the TME while eliciting rapid and enduring cancer immunotherapy.
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Full text: 1 Database: MEDLINE Main subject: RNA / Tumor Microenvironment / Immunotherapy / Lipids Limits: Animals / Female / Humans Language: En Journal: Cell Year: 2024 Type: Article Affiliation country: United States
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Full text: 1 Database: MEDLINE Main subject: RNA / Tumor Microenvironment / Immunotherapy / Lipids Limits: Animals / Female / Humans Language: En Journal: Cell Year: 2024 Type: Article Affiliation country: United States