Novel anti-brain tumor cytotoxins specific for cancer cells.
The vast majority of brain cancers (gliomas) express a receptor (R) for interleukin 13 (IL13). In order to achieve specific targeting of the IL13R in gliomas, we have mutagenized human (h) IL13. The mutation was made to alter IL13 interaction with the shared functional IL13/4 normal tissue receptor, but not with the glioma-associated receptor. We have thus produced hIL13.E13K (glutamic acid at position 13 changed to lysine) and fused it to derivatives of Pseudomonas exotoxin A. The hIL13.E13K-based cytotoxins are less active on normal cells and thus less toxic, and are better antitumor agents compared with the cytotoxins containing nonmutagenized hIL13.
Debinski
W
W
Department of Surgery, Pennsylvania State University College of Medicine, Hershey 17033-0850, USA. wdebinski@psghs.edu
Gibo
D M
DM
Obiri
N I
NI
Kealiher
A
A
Puri
R K
RK
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000235:genetics; D002352:Carrier Proteins; D002455:Cell Division / Q000187:drug effects / Q000235:genetics; D003603:Cytotoxins / Q000627:therapeutic use*; D005098:Exotoxins / Q000235:genetics / Q000627:therapeutic use*; D005910:Glioma / Q000188:drug therapy* / Q000235:genetics; D018698:Glutamic Acid; D006801:Humans; D018793:Interleukin-13 / Q000235:genetics; D053661:Interleukin-13 Receptor alpha1 Subunit; D008239:Lysine; D009154:Mutation / Q000235:genetics; D010957:Plasmids; D011550:Pseudomonas aeruginosa; D011956:Receptors, Cell Surface / Q000235:genetics*; D018123:Receptors, Interleukin / Q000187:drug effects / Q000235:genetics*; D053660:Receptors, Interleukin-13; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000627:therapeutic use; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D002352:Carrier Proteins; D003603:Cytotoxins; D005098:Exotoxins; C508181:IL13RA1 protein, human; C508183:Il13ra1 protein, mouse; D018793:Interleukin-13; D053661:Interleukin-13 Receptor alpha1 Subunit; C027553:Pseudomonas exotoxin binding protein, mouse; D011956:Receptors, Cell Surface; D018123:Receptors, Interleukin; D053660:Receptors, Interleukin-13; D011993:Recombinant Fusion Proteins; D018698:Glutamic Acid; D008239:Lysine