Targeted delivery of antitumoral therapy to glioma and other malignancies with synthetic chlorotoxin (TM-601).
Targeted therapies for cancer is a rapidly advancing field, but the identification of tumor-specific ligands has proven difficult. Chlorotoxin (CTX) is a small, 36 amino acid neurotoxin isolated from the venom of the Giant Yellow Israeli scorpion Leiurus Quinquestriatus. Interestingly, the peptide has been found to preferentially bind to a variety of human malignancies, but shows little or no binding to normal human tissues. A synthetic version of this peptide (TM-601) has been manufactured and covalently linked to iodine 131 (131I-TM-601) as a means of targeting radiation to tumor cells. Preclinical studies and Phase I clinical trials have been completed in patients with recurrent glioma, a type of malignant brain tumor. These studies demonstrated that intracavitary dosing of 131I-TM-601 appears safe, minimally toxic, and binds malignant glioma with high affinity and for long durations. A Phase II trial of this agent using higher doses of radioactivity and repeated local administrations is underway. In addition, enrolment has begun in a Phase I trial evaluating whether systemically delivered 131I-TM-601 can be used to image metastatic solid tumors and primary gliomas. Due to its small size, selective tumor binding properties, minimal toxicity and relative ease of manipulation, CTX represents a potentially important targeting agent for many cancers.
Mamelak
Adam N
AN
Cedars-Sinai Medical Center, Maxine Dunitz Neurosurgical Institute, Department of Neurosurgery, Los Angeles, CA8631 W. Third Street, Suite 800e, Los Angeles, CA 90048, USA. mamelaka@cshs.org
Jacoby
Douglas B
DB
D000818:Animals; D001932:Brain Neoplasms / Q000532:radiotherapy*; D002986:Clinical Trials as Topic; D004353:Drug Evaluation, Preclinical; D005910:Glioma / Q000532:radiotherapy*; D006801:Humans; D007457:Iodine Radioisotopes / Q000008:administration & dosage* / Q000627:therapeutic use; D011817:Rabbits; D012604:Scorpion Venoms / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014018:Tissue Distribution
D007457:Iodine Radioisotopes; D012604:Scorpion Venoms; C091539:Chlorotoxin