title: Interleukin-13 Displaying Retargeted Oncolytic Measles Virus Strains Have Significant Activity Against Gliomas With Improved Specificity.
abstract: The majority of glioblastoma multiforme (GBM) tumors (80%) overexpress interleukin-13 receptor α2 (IL-13Rα2), but there is no expression of IL-13Rα2 in normal brain. Vaccine strains of measles virus have significant antitumor activity against gliomas. We tested the hypothesis that measles virus entry could be retargeted via the IL-13Rα2. MV-GFP-HAA-IL-13 was generated from the Edmonston-NSe vaccine strain, by displaying human IL-13 at the C-terminus of the H protein, and introducing CD46 and signaling lymphocyte activation molecule (SLAM)-ablating mutations in H. The IL-13 retargeted virus showed significant cytopathic effect (CPE) against IL-13Rα2 overexpressing glioma lines, and lack of CPE/viral replication in normal human astrocytes and normal human fibroblasts not expressing IL-13Rα2. In vivo treatment of orthotopically implanted GBM12 xenografts demonstrated significant prolongation of survival in mice treated with the retargeted strain (P < 0.0001), and comparable activity between the IL-13R retargeted strain and MV-GFP (P = 0.6377). In contrast to MV-GFP-treated mice, administration of the retargeted strain in the central nervous system of measles replication-permissive IfnarkoCD46 Ge mice resulted in lack of neurotoxicity. Strains of measles virus retargeted against the glioma-specific IL-13Rα2 receptor have comparable therapeutic efficacy, and improved specificity as compared with the unmodified measles virus strain MV-GFP in vitro and in vivo.
authors.affiliation: Molecular Medicine Department, Mayo Clinic College Of Medicine, Rochester, Minnesota, USA.
authors.forename: Cory
authors.initials: C
authors.lastname: Allen
authors.affiliation: Molecular Medicine Department, Mayo Clinic College Of Medicine, Rochester, Minnesota, USA.
authors.forename: Georgia
authors.initials: G
authors.lastname: Paraskevakou
authors.affiliation: Molecular Medicine Department, Mayo Clinic College Of Medicine, Rochester, Minnesota, USA.
authors.forename: Ianko
authors.initials: I
authors.lastname: Iankov
authors.affiliation: Division of Anatomic Pathology, Mayo Clinic College Of Medicine, Rochester, Minnesota, USA.
authors.forename: Caterina
authors.initials: C
authors.lastname: Giannini
authors.affiliation: Radiation Oncology Research, Mayo Clinic College Of Medicine, Rochester, Minnesota, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Schroeder
authors.affiliation: Radiation Oncology Research, Mayo Clinic College Of Medicine, Rochester, Minnesota, USA.
authors.forename: Jann
authors.initials: J
authors.lastname: Sarkaria
authors.affiliation: US Food and Drug Administration, Rockville, Maryland, USA.
authors.forename: Raj K
authors.initials: RK
authors.lastname: Puri
authors.affiliation: Molecular Medicine Department, Mayo Clinic College Of Medicine, Rochester, Minnesota, USA.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Russell
authors.affiliation: Molecular Medicine Department, Mayo Clinic College Of Medicine, Rochester, Minnesota, USA; Department of Oncology, Mayo Clinic College Of Medicine, Rochester, Minnesota, USA. Electronic address: galanis.evanthia@mayo.edu.
authors.forename: Evanthia
authors.initials: E
authors.lastname: Galanis