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Gene therapy eliminates brain tumors through selective recruitment of immune cells
Date:1/12/2009

LOS ANGELES (January 13, 2009) Scientists seeking to harness the power of the immune system to eradicate brain tumors face two major hurdles: recruiting key immune cells called dendritic cells into areas of the brain where they are not naturally found and helping them recognize tumor cells as targets for attack.

Researchers at Cedars-Sinai Medical Center, however, have identified a sequence of molecular events that accomplish both objectives. Their findings, based on laboratory and animal studies, appear in the Jan. 13 issue of PLoS Medicine, an open-access online journal of the Public Library of Science.

The Cedars-Sinai team discovered that a protein HMGB1 released from dying tumor cells activates dendritic cells and stimulates a strong and effective anti-tumor immune response. HMGB1 does so by binding to an inflammatory receptor called toll-like receptor 2, or TLR2, found on the surface of dendritic cells.

"Toll receptors play a major role in the immune system's recognition of bacterial and viral components, but now we have shown that they also trigger an immune response against tumors," said Maria G. Castro, Ph.D., co-director of Cedars-Sinai's Board of Governors Gene Therapeutics Research Institute and one of the article's senior authors. "Activation of Toll receptors was essential for two key stages in initiating immune responses against the tumor the migration of peripheral dendritic cells into the brain tumor and the subsequent activation of dendritic cells and stimulation of a specific anti-tumor cytotoxic T-cell mediated response."

Building on more than 10 years of research in this area, the researchers used a combined gene therapeutic approach, using one protein (Flt3L) to draw dendritic cells from bone marrow into the brain tumors, and a second protein (Herpes Symplex type I Thymidine Kinase, or TK), combined with the antiviral gancyclovir to kill tumor cells and elicit long-term survival. In th
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Contact: Simi Singer
simi.singer@cshs.org
310-423-7798
Cedars-Sinai Medical Center
Source:Eurekalert

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