HMGB1 binds to TLR2 and increased survival in brain-tumor models, according to PLoS Medicine paper.

Researchers at Cedars-Sinai Medical Center discovered that when the protein HMGB1 is released from fading tumor cells it activates dendritic cells and stimulates a strong and effective antitumor immune response.


HMGB1 accomplishes the task by binding to the inflammatory receptor toll-like receptor 2 (TLR2), which is found on the surface of dendritic cells. This results in the activation and expansion of tumor-antigen specific T cells. The process caused the regression of brain tumors and increased survival time by six months in experimental brain tumor models.


“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,” remarks Maria G. Castro, Ph.D., co-director of Cedars-Sinai’s Board of Governors Gene Therapeutics Research Institute. “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 antitumor cytotoxic T-cell mediated response.”


The investigators employed 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) combined with the antiviral gancyclovir to kill tumor cells and elicit long-term survival.


The article appears in the January 13 issue of PLoS Medicine.



 

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