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Intratumoral
administration of recombinant circularly permuted interleukin-4-Pseudomonas
exotoxin in patients with high-grade glioma
Rand RW, Kreitman RJ, Patronas N, Varricchio F, Pastan
I, Puri RK
Department
of Neuro-Oncology, John Wayne Cancer Institute, Santa Monica, California 90404,
USA
Human
glioblastoma but not normal brain cells express numerous receptors for the
cytokine interleukin (IL)-4.
To target these receptors, we have investigated the safety and activity of
directly infusing IL-4(38-37)-PE38KDEL, a chimeric protein composed of
circularly permuted IL-4 and a truncated form of Pseudomonas exotoxin (PE), into
recurrent malignant high-grade gliomas.
IL-4(38-37)-PE38KDEL (IL-4-toxin) was infused over a 4-8-day period into gliomas
of nine patients by one to three stereotactically placed catheters.
No apparent systemic toxicity occurred in any patient.
The infusion of IL-4-toxin in six of nine patients showed glioma necrosis as
evidenced by diminished gadolinium enhancement on magnetic resonance
imaging.
Seven of nine patients underwent craniotomy because of increased intracranial
pressure at 16-101 days after the beginning of infusion.
In six of these seven patients, partial-to-extensive tumor necrosis with edema
was confirmed pathologically.
No histological evidence of neurotoxicity to normal brain was identified in any
patient.
Two patients were not operated on; by magnetic resonance imaging, one showed
mottled gadolinium enhancement, and the other showed extensive necrosis of tumor
leading to complete remission; this patient remains disease-free > 18 months
after the procedure.
We conclude that direct glioma injection of IL-4(38-37)-PE38KDEL is safe without
systemic toxicity.
Local toxicity seemed attributable mainly to tumor necrosis or occasionally to
the volume of infusion.
Histological evidence of toxicity to normal brain was not observed and in many
patients, could be pathologically excluded.
Additional patients are being
treated to determine the maximal tolerated concentration and volume of
IL-4(38-37)-PE38KDEL.
PMID:
10873064 [PubMed - indexed for MEDLINE]
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