title: Recombinant Sendai virus vector induces complete remission of established brain tumors through efficient interleukin-2 gene transfer in vaccinated rats.
abstract: OBJECTIVE
  Sendai virus (SeV), a murine parainfluenza virus type I, replicates independent of cellular genome and directs high-level gene expressions when used as a viral vector. We constructed a nontransmissible recombinant SeV vector by deleting the matrix (M) and fusion (F) genes from its genome (SeV/DeltaMDeltaF) to enhance its safety. We also estimated the therapeutic efficacy of the novel vector system against a rat glioblastoma model.
  
  
  METHODS
  We administered the recombinant SeV vector carrying the lacZ gene or the human interleukin-2 (hIL-2) gene into established 9L brain tumors in vivo simultaneous with peripheral vaccination using irradiated 9L cells. Sequential monitoring with magnetic resonance imaging was used to evaluate the therapeutic efficacy.
  
  
  RESULTS
  We found extensive transduction of the lacZ gene into the brain tumors and confirmed sufficient amounts of interleukin 2 (IL-2) production by hIL2-SeV/DeltaMDeltaF both in vitro and in vivo. The magnetic resonance imaging study showed that the intracerebral injection of hIL2-SeV/DeltaMDeltaF brought about significant reduction of the tumor growth, including complete elimination of the established brain tumors. The (51)Cr release assay showed that significant amounts of 9L-specific cytotoxic T cells were induced by the peripheral vaccination. Immunohistochemical analysis revealed that CD4(+) T cells and CD8(+) T cells were abundantly infiltrated in the target tumors.
  
  
  CONCLUSIONS
  The present results show that the recombinant nontransmissible SeV vector provides efficient in vivo gene transfer that induces significant regression of the established brain tumors and suggest that it will be a safe and useful viral vector for the clinical practice of glioma gene therapy.
authors.affiliation: Department of Neurological Surgery, Graduate School of Medicine, Chiba University, Japan. iwadatey@faulty.chiba-u.jp
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Iwadate
authors.forename: Makoto
authors.initials: M
authors.lastname: Inoue
authors.forename: Takashi
authors.initials: T
authors.lastname: Saegusa
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Tokusumi
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kinoh
authors.forename: Mamoru
authors.initials: M
authors.lastname: Hasegawa
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Tagawa
authors.forename: Akira
authors.initials: A
authors.lastname: Yamaura
authors.forename: Hideaki
authors.initials: H
authors.lastname: Shimada
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000235:genetics* / Q000628:therapy* / Q000662:veterinary; D004195:Disease Models, Animal; D018014:Gene Transfer Techniques; D005818:Genetic Engineering; D005822:Genetic Vectors; D005909:Glioblastoma / Q000235:genetics* / Q000628:therapy* / Q000662:veterinary; D005910:Glioma / Q000473:pathology; D018316:Gliosarcoma / Q000473:pathology; D007376:Interleukin-2 / Q000235:genetics* / Q000494:pharmacology*; D007668:Kidney / Q000166:cytology; D008253:Macaca mulatta; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D029082:Sendai virus / Q000235:genetics*; D019076:Transgenes
chemical_list: D007376:Interleukin-2