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Intracranial therapy of glioblastoma with the fusion protein DTIL13 in immunodeficient mice
Author(s) -
Rustamzadeh Edward,
Hall Walter A.,
Todhunter Deborah A.,
Low Walter C.,
Liu Haiying,
PanoskaltsisMortari Angela,
Vallera Daniel A.
Publication year - 2006
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.21647
Subject(s) - toxicity , in vivo , diphtheria toxin , medicine , pathology , magnetic resonance imaging , brain tumor , biology , toxin , radiology , biochemistry , microbiology and biotechnology
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. © 2005 Wiley‐Liss, Inc.