Lab study: Protein delivered via genetically engineered virus slowed glioblasoma multifo...( erapeutic agents to the brain. Most of...),Health

erapeutic agents to the brain. Most of these have investigated the use of the suicide gene from the herpes simplex virus to develop a gene therapy approach that kills cancer cells, in the presence of the antiviral drug, gancyclovir. In laboratory studies, this type of gene therapy has proved almost 100 percent effective. But in clinical trials, it has had limited effectiveness, suggesting that the virus is not able to deliver the suicide gene effectively into a large tumor mass.

"Importantly, results from these studies showed us that gene therapy was safe, but that we needed to design a viral vector that would harness the power of the immune system to help eliminate the tumor," commented Dr. Castro.

Genetically engineered viruses are used to transport genes and/or proteins into cells and have been used in gene therapy research for the last ten years. Just like a viral infection, they work by tricking cells into accepting them as part of their own genetic coding. To make them safe, scientists remove the genetic viral genes that cause infection and engineer them so that they stop reproducing and also carry therapeutic genes.

In this study, researchers from the "Gene Therapeutics Research Institute" team, led by Drs. Castro and Pedro Lowenstein, investigated the effectiveness of an anti-brain tumor therapy using hsFlt3L, a protein that has a unique ability to increase the number of immune cells when delivered into the brain. Specifically, these immune cells are called dendritic cells and work by presenting antigens or foreign invaders that enter the body and inducing the generation of cell-killing T-lymphocytes.

Because the brain lacks dendritic cells and is protected by the blood brain barrier, the investigators tested an adenoviral vector that had been genetically manipulated to selectively express hsFlt3L to find out if it would increase the number of dendritic cells in the brain of laboratory rats with
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Contact: Kelli Hanley
kelli.hanley@cshs.org
310-423-3674
Cedars-Sinai Medical Center
6-Dec-2004

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