Glioblastoma multiforme is the most common primary malignant
brain tumor and despite treatment with surgery, radiation, and
chemotherapy, the median survival of patients with
glioblastoma multiforme is approximately 1 year.
Glioblastoma multiforme explants and cell lines have been reported to overexpress the
interleukin-13 receptor alpha2 subunit (
IL13Ralpha2) relative to nonneoplastic brain. Based on this finding, a recombinant
cytotoxin composed of
IL13 ligand and a truncated form of
Pseudomonas aeruginosa exotoxin A (IL13-PE38QQR) was developed for the targeted treatment of
glioblastoma multiforme tumors. In a recently completed phase III clinical trial, however,
IL13-PE38QQR was found to be no more effective than an existing
therapy in prolonging survival. To determine possible explanations for this result, we analyzed the relative expression levels of
IL13Ralpha2 in
glioblastoma multiforme and nonneoplastic brain specimens using publicly available
oligonucleotide microarray databases, quantitative real-time reverse transcription PCR, and immunohistochemical staining. Increased expression of the
IL13Ralpha2 gene relative to nonneoplastic brain was observed in 36 of 81 (44%) and 8 of 17 (47%)
tumor specimens by microarray and quantitative real-time reverse transcription PCR analyses, respectively. Immunohistochemical staining of
tumor specimens showed highly variable expression of
IL13Ralpha2 protein both within and across specimens. These data indicate that prescreening of subjects may be of benefit in future trials of
IL13Ralpha2 targeting
therapies.