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New monoclonal antibody inhibits tumor growth in advanced solid tumors in phase I clinical trial
Date:11/6/2012

A newly developed antibody targeting a signalling pathway that is frequently active in solid tumours has shown encouraging signs of efficacy in its first trial in humans, researchers will report at the 24th EORTC-NCI-AACR [1] Symposium on Molecular Targets and Cancer Therapeutics in Dublin, Ireland, today (Wednesday). [2]

A patient with advanced malignant melanoma has shown signs of tumour shrinkage and has been receiving treatment for more than 30 weeks without any serious adverse side-effects. Other patients with advanced non-small cell lung cancer (NSCLC), mesothelioma, kidney cancer and biliary tract cancer also have had extended treatments with stable disease.

The compound is a monoclonal antibody known as RG7212. It targets a soluble protein in the blood called TWEAK (Tumour Necrosis Factor (TNF)-like weak inducer of apoptosis. TWEAK binds to the receptor Fn14 (fibroblast growth factor-inducible 14) on the cell membrane, and this is the signal for a cascade of subsequent events, including activation of multiple cancer-promoting pathways. One objective of this phase I trial was to determine whether blocking of TWEAK-Fn14 signalling with RG7212 would reduce activation of these pathways.

Dr Ulrik Lassen (MD, PhD), head of the oncology phase I unit at the Rigshospitalet, Copenhagen, Denmark, will tell the Symposium: "TWEAK and Fn14 are a pair of cell signalling molecules that are part of the large family of tumour necrosis factors that play a number of roles in the development of cancer. The Fn14-receptor is over-expressed in a variety of advanced solid tumours, and signalling through TWEAK-Fn14 enhances multiple processes associated with malignancy.

"Preclinical data have shown that the RG7212 monoclonal antibody successfully targets and blocks the action of TWEAK and that it works most effectively in tumour cells where there is increased Fn14 expression. Therefore, we expected that using RG7212 to block TWEAK signalling i
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Contact: Emma Mason
wordmason@mac.com
ECCO-the European CanCer Organisation
Source:Eurekalert

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