Interstitial infusion of IL13-PE38QQR in the rat brain stem.
Interstitial infusion of IL13-PE38QQR, a tumor specific, chimeric cytotoxin, into the rat brain stem was performed in an effort to assess safety. Six rats underwent stereotaxic cannula placement into the pontine segment of the brain stem followed by a 24-h infusion of IL13-PE38QQR (volume of infusion (Vi) 200 microl) at a concentration of 10 microg/ml. The animals were assessed neurologically and then sacrificed either immediately or after 2 weeks. All animals tolerated the infusions without exhibiting any neurological changes. Postmortem examination of the brains revealed no significant histological changes beyond the site of the cannula tract. These findings indicate that supratherapeutic concentrations of IL13-PE38QQR administered by interstitial infusion into the rat brain stem is well tolerated and may serve as a potential therapeutic strategy for children with diffuse pontine gliomas.
Souweidane
Mark M
MM
Department of Neurological Surgery, Weill Medical College of Cornell University, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. mmsouwei@med.cornell.edu
Occhiogrosso
Giuseppe
G
Mark
Erika B
EB
Edgar
Mark A
MA
D036002:ADP Ribose Transferases / Q000235:genetics; D000818:Animals; D001427:Bacterial Toxins / Q000235:genetics; D001933:Brain Stem / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005098:Exotoxins / Q000235:genetics; D000922:Immunotoxins / Q000008:administration & dosage* / Q000633:toxicity; D007260:Infusion Pumps; D007263:Infusions, Parenteral; D018793:Interleukin-13 / Q000008:administration & dosage* / Q000633:toxicity; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000633:toxicity; D013238:Stereotaxic Techniques; D037521:Virulence Factors / Q000235:genetics; D000097668:Pseudomonas aeruginosa Exotoxin A
D036002:ADP Ribose Transferases; D001427:Bacterial Toxins; D005098:Exotoxins; D000922:Immunotoxins; D018793:Interleukin-13; D011993:Recombinant Fusion Proteins; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A; C521502:IL13-PE38