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Novel Gene Therapy for Brain Tumor Nears Clinical Trial

Last Updated: July 02, 2009.

A novel gene therapy for glioblastoma multiforme utilizing a combination of adenoviral vectors and the drug ganciclovir is nearing clinical trial with the discovery of a biomarker to gauge tumor response to the treatment, according to a study reported in the July 1 issue of Clinical Cancer Research.

THURSDAY, July 2 (HealthDay News) -- A novel gene therapy for glioblastoma multiforme utilizing a combination of adenoviral vectors and the drug ganciclovir (GCV) is nearing clinical trial with the discovery of a biomarker to gauge tumor response to the treatment, according to a study reported in the July 1 issue of Clinical Cancer Research.

Marianela Candolfi, Ph.D., of the University of California in Los Angeles, and colleagues implanted glioblastoma cells in the brains of rats treated with either adenoviral vectors (Ad) encoding the cytokine Flt3L (Ad-Flt3L) and thymidine kinase (Ad-TK); adenoviral vectors encoding the proapoptotic cytokines (tumor necrosis factor-α, tumor necrosis factor-related apoptosis-inducing factor and Fas ligand [FasL] alone); or the adenoviral vectors encoding the proapoptotic cytokines in combination with Ad-Flt3L. After the delivery of the viral vectors, the rats were treated with the GCV.

The researchers found that, in rats with small tumors, Ad-TK+GCV or Ad-FasL improved survival. For rats with large tumors, Ad-Flt3L combined with Ad-TK+GCV led to 70 percent long-term survival, while Ad-Flt3L with Ad-FasL did not improve survival. All of the treatments resulted in the release of the high mobility group box 1 protein by the dying tumor cells, providing a biomarker for the efficacy of the treatment in a proposed clinical trial.

"Our results indicate that Ad-TK+GCV+Ad-Flt3L exhibits the highest efficacy and safety profile among the several proapoptotic approaches tested. The results reported further support for the implementation of this combined approach in a phase I clinical trial for GBM," the authors conclude.

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