Product Code Database
Chlorotoxin is a 36-amino acid peptide found in the venom of the Deathstalker ( Leiurus quinquestriatus) which blocks small-conductance . The fact that chlorotoxin binds preferentially to glioma cells has allowed the development of methods for the treatment and diagnosis of several types of cancer.
Using a recombinant chlorotoxin it was demonstrated that chlorotoxin specifically and selectively interacts with MMP-2 isoforms which are specifically upregulated in gliomas and related cancers, but are not normally expressed in brain.
Chlorotoxin has the ability to interact with chloride channels in membrane protein in glioma cells, so this prevents transmembrane chloride fluxes but this interaction does not happen for the neurons and normal glial cells. This suggests a potential treatment for cancer.
A report showed the anti-invasive effect of chlorotoxin on glioma cells mediated by its interaction with MMP-2, which allows the penetration of normal and tumor cells through tissue barriers. Chlorotoxin exerts a dual effect on MMP-2: it inhibits the enzymatic activity of MMP-2 and causes a reduction in the surface expression of MMP-2. This result implies the use of chlorotoxin as a highly effective drug of therapeutic potential for diseases that involve the activity of MMP-2.
TM-601 which is the synthetic version of chlorotoxin is under phase II clinical trial. Iodine-131-TM-601 is used to treat malignant glioma. TM-601 is also a candidate for targeting gliomas because it crosses blood-brain and tissue barriers and binds to malignant brain tumor cells without affecting healthy tissue.
Phase II trials are being conducted on the use of chlorotoxin for imaging and radio therapy in glioma.
Chlorotoxin:Cy5.5 (CTX:Cy5.5), which is a bioconjugate of chlorotoxin and a fluorescent dye named Cyanine, was used by researchers at Seattle Children's Hospital Research Institute and Fred Hutchinson Cancer Research Center to distinguish cancer cells from the surrounding normal cells. This could enable surgeons to remove cancerous cells without injuring the surrounding healthy tissue. CTX:Cy5.5 is a fluorescent molecule emitting photons in the near infrared spectrum and hence can be visualized in the operating room with the aid of infrared glasses. Studies in mouse models have shown that CTX:Cy5.5 can identify tumors with as few as 2000 cancer cells, making it 500 times more sensitive than MRI. Treated animals exhibited no neurologic or behavioral deficits, and postmortem studies revealed no evidence of neuropathy. In 2015, clinical trials were beginning for this "Tumor Paint."
|
|
