On the TRAIL of therapeutic antibody treatments
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Monoclonal antibodies are important research tools in the fight against cancer. But they have also proven to be powerful therapeutic tools in their own right, owing to their ability to target specific proteins expressed by tumour cells. Recently, researchers at the Wistar Institute used TRAIL antibody products to develop a new combination therapy for malignant brain tumors.
TRAIL (TNF-related apoptosis-inducing ligand) is a pro-apoptotic type II membrane protein, belonging to the TNF family. The TRAIL ligand induces apoptosis by binding to the death domain receptors DR4/DR5, activating the caspase cascade which leads to chromosomal DNA degradation. TRAIL antibody studies have also identified two decoy receptors, DcR1 and DcR2. These have a TRAIL binding domain but lack the death domain, and so do not initiate apoptosis.
In recent years, a number of monoclonal antibody therapies have been developed for cancer. Strategies include targeted binding to tumor-related antigens; induction of apoptosis; antibody-dependent cytotoxicity; and growth factor receptor inhibition. TRAIL receptor-targeted cancer therapy represents a new avenue of approach. Since 2004, several monoclonal antibodies specific to tumor-cell TRAIL DR-receptors have been developed. These were proposed as more advantageous than the TRAIL ligand for inducing apoptosis, as TRAIL also targets the DcR receptors, in addition to which it requires a more frequent and intensive dosing regimen. In animal models, these were most efficacious when combined with other treatments.
The latest clinical research looked at the concept of TRAIL-ligand binding, as a way to treat glioblastoma brain tumors. Previous antibody studies showed that TRAIL alone was ineffective at promoting apoptosis in glioblastoma cells. However, low doses of Gamitrinib sensitized tumour-cell death receptors to TRAIL-binding, stimulating mitochondrial damage and apoptosis. Gamitrinib is an inhibitor of the heat-shock protein Hsp90, and at low doses promotes a stress-related response which suppresses the anti-apoptotic protein NF-??, allowing TRAIL to work.
We at Novus Biologicals have an extensive range of high quality antibody products in our antibody catalog, which are widely used in the research and development of new cancer therapies. |
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The Article is written by www.novusbio.com providing Antibody Catalogue and Antibody Database. Visit http://www.novusbio.com for more information on www.novusbio.com Products and Services___________________________Copyright information This article is free for reproduction but must be reproduced in its entirety, including live links and this copyright statement must be included. Visit www.novusbio.com for more services!
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By :
Brigette Federico
Submitted
2011-06-27 02:54:27 |
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