Intracranial therapy of glioblastoma with the fusion protein DTIL13 in immunodeficient mice

Edward Rustamzadeh, Walter A. Hall, Deborah A. Todhunter, Walter C. Low, Haiying Liu, Angela Panoskaltsis-Mortari, Daniel A. Vallera

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

A fusion protein consisting of human interleukin-13 and the first 389 amino acids of diphtheria toxin was assembled in order to target human glioblastoma cell lines in a murine intracranial model. In vitro studies to determine specificity indicated that the protein called DTIL13 was highly selective for human glioblastoma. In vivo, the maximum tolerated dose of DTIL13 was 1 μg/injection given every other day and repeated for 3 days. Doses that exceeded this amount resulted in weight loss and liver damage as determined by histology and enzyme assay. Experiments in IL-4 receptor knockout mice revealed that liver toxicity was receptor-related. This same dose given to nude mice with established U373 MG brain tumors resulted in significant reductions in tumor volume and significantly prolonged survival (p < 0.0001). Magnetic resonance imaging (MRI) proved to be extremely useful in (i) determining the ability of DTIL13 to reduce tumor size and (ii) for studying toxicity since diffusion-weighted and gradient echo-weighted MRI revealed that vascular leak syndrome was not a limiting toxicity at this dose. These results suggest that DTIL13 is as effective in an intracranial rodent model as it was in a flank model in previous studies and that DTIL13 might be an effective treatment for glioblastoma multiforme.

Original languageEnglish (US)
Pages (from-to)2594-2601
Number of pages8
JournalInternational Journal of Cancer
Volume118
Issue number10
DOIs
StatePublished - May 15 2006

Keywords

  • Brain tumor
  • Diphtheria toxin
  • Glioblastoma
  • Immunotoxin
  • Interleukin-13

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