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Antibody targeting of glioblastoma shows promise in preclinical tests, say Lombardi researchers
Date:7/31/2009

developing, it needs to constantly remodel itself," he says. "Glioblastoma appears to be another example of cancer that develops when embryonic genes are upregulated. As a result, brain tumor cells are extremely motile and can invade other parts of the brain very quickly."

In this latest research, Wellstein and his colleagues searched public databases, at the National Library of Medicine, to see if other studies that collected and analyzed glioblastoma and other brain tumor tissues also recorded expression of PTN and ALK, as well as genes along this pathway. "We found that they are significantly up regulated," he says. They then assessed whether that activity mattered to the outcome of patients with brain tumors. "A lot of pathways that are activated in cancer are passengers, in a sense. They don't drive cancer. But in the case of PTN and ALK, the expression data suggest that these are drivers patients with increased expression of these genes had significantly poorer outcomes in an analysis of different, independent studies."

Wellstein had also been working on a method to shut off the pathway. Several years ago, GUMC investigators found the "sweet spot" on ALK where PTN binds, which Wellstein says was a major discovery. "You can have hundreds of different areas on a receptor protein where its ligand could theoretically bind. We found just the right one."

They collaborated with ESBAtech in Switzerland who created a small single-chain antibody fragment in yeast that would itself bind to the sweet spot, blocking ALK's interaction with PTN. In the present study, the researchers successfully tested the antibody in human glioblastoma cells, and also showed that in mice implanted with human glioblastoma, the antibody prevented tumors from growing. For example untreated tumors grew to an average size of 350 cubic millimeters after three weeks, but treated tumors did not grow beyond their initial 25 cubic millimeters.

Wellstein says a ph
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Contact: Karen Mallet
km463@georgetown.edu
215-514-9751
Georgetown University Medical Center
Source:Eurekalert

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