Cintredekin besudotox in treatment of malignant glioma.
BACKGROUND
Interleukin-13 (IL-13) receptors are overexpressed in glioblastoma multiforme (GBM). The presence of IL-13 binding sites in GBM and their absence in normal brain tissue validates IL-13 receptor as an important target in human GBM.


OBJECTIVE
This review discusses the bench-to-bedside experience with a recombinant cytotoxin composed of human IL-13 and a truncated form of Pseudomonas exotoxin A (PE38QQR), delivered via convection-enhanced delivery (CED), in GBM treatment.


METHODS
The authors review publications regarding the laboratory research and clinical development of IL-13-directed therapies and summarize the future of IL-13-targeted cytotoxin.


CONCLUSIONS
The IL-13 receptor remains an important potential target in GBM, and preliminary experience with the IL-13-PE38QQR cytotoxin (also called cintredekin besudotox) has helped to pave the way for study of CED as an important means of drug delivery to malignant gliomas. Ongoing analysis of recently completed clinical trials will determine the future of this agent and its potential therapeutic targets.
Mut
Melike
M
Hacettepe Hastanesi Beyin Cerrahisi, Bolum 71 Sihhiye, Ankara 06100, Turkey. mm2ee@virginia.edu
Sherman
Jonathan H
JH
Shaffrey
Mark E
ME
Schiff
David
D
D036002:ADP Ribose Transferases / Q000494:pharmacology / Q000627:therapeutic use*; D019943:Amino Acid Substitution; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D001427:Bacterial Toxins / Q000494:pharmacology / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data; D004333:Drug Administration Routes; D016503:Drug Delivery Systems; D005098:Exotoxins / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D005909:Glioblastoma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D000922:Immunotoxins / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D018793:Interleukin-13 / Q000008:administration & dosage / Q000009:adverse effects / Q000037:antagonists & inhibitors / Q000235:genetics / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D009363:Neoplasm Proteins / Q000187:drug effects; D053660:Receptors, Interleukin-13 / Q000187:drug effects; D011993:Recombinant Fusion Proteins; D016879:Salvage Therapy; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured / Q000187:drug effects; D037521:Virulence Factors / Q000494:pharmacology / Q000627:therapeutic use*; D023041:Xenograft Model Antitumor Assays; D000097668:Pseudomonas aeruginosa Exotoxin A
D036002:ADP Ribose Transferases; D000970:Antineoplastic Agents; D001427:Bacterial Toxins; D005098:Exotoxins; D000922:Immunotoxins; D018793:Interleukin-13; D009363:Neoplasm Proteins; D053660:Receptors, Interleukin-13; D011993:Recombinant Fusion Proteins; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A; C521502:IL13-PE38