Novel way to increase targeting specificity to a human glioblastoma-associated receptor for interleukin 13.
Human brain cancers (gliomas) overexpress large numbers of a receptor for interleukin 13 (IL13), making this receptor an attractive target for anti-glioma therapies. We have recently proposed that the glioma-associated IL13 receptor is different from the one expressed on some hemopoietic and somatic cells. In an attempt to identify an even more glioma-specific target, we have used an antagonist of a related cytokine, IL4, which neutralizes the physiological effects of both IL13 and IL4 on normal cells. Here we demonstrate that the IL4 antagonist also counteracts the action of cytotoxins targeted to the IL13 receptor on normal human cells. Importantly, the IL4 antagonist does not inhibit IL13-based cytotoxins on glioma cells at all. Thus, the IL13 receptor on glioma cells can be categorized as tumor-specific in the presence of an IL4 antagonist. We conclude that IL13 receptor-directed cytotoxins can be delivered to glioma cells without being cytotoxic to normal cells.
Debinski
W
W
Section of Neurosurgery, Pennsylvania State University College of Medicine, Hershey 17033-0850, USA. wdebinski@PSGHS.EDU
Gibo
D M
DM
Puri
R K
RK
D036002:ADP Ribose Transferases; D000230:Adenocarcinoma / Q000473:pathology; D001427:Bacterial Toxins / Q000494:pharmacology; D001932:Brain Neoplasms / Q000378:metabolism*; D004727:Endothelium / Q000187:drug effects; D005098:Exotoxins / Q000494:pharmacology*; D005909:Glioblastoma / Q000378:metabolism*; D006801:Humans; D018793:Interleukin-13 / Q000378:metabolism*; D011550:Pseudomonas aeruginosa; D018123:Receptors, Interleukin / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A
D036002:ADP Ribose Transferases; D001427:Bacterial Toxins; D005098:Exotoxins; D018793:Interleukin-13; D018123:Receptors, Interleukin; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A