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Lab study: Protein delivered via genetically engineered virus slowed glioblasoma multiforme growth

GBM.

To evaluate whether hsFlt3L could shrink brain tumors and prolong survival, rats with GBM were injected with increasing doses of the engineered virus expressing hsFlt3L or a saline placebo that was used as a control. The investigators found that 70 percent of the rats treated with hsFlt3L survived long-term, for over a year, when the higher dose was used, and that it did not cause adverse immune reactions in the normal brain. In contrast, the rats treated with placebo substances died from their tumors within one week after the start of the treatment.

"Taking into account both the effectiveness of the treatment in the preclinical GBM animal model and also the lack of overt adverse side effects to the surrounding normal brain, we hope to start clinical trials using this combined immune and suicide gene therapy approach within the next three years," said Dr Castro.

Among rats treated with hsFlt3L, the investigators found that 33 percent were completely tumor free at three months, while all those who survived for six months or longer had no tumors at all. Moreover, no rats died between the three and six months' time points.

"These results show that tumor growth was greatly inhibited in rats treated with hsFlt3L and reflect an ongoing battle between the tumor and the immune system," said Dr. Castro. "In other words, hsFlt3L stimulated an immune response as evidenced by an increase in the number of dendritic cells in the brain and led to complete elimination of the tumor in most of the rats, while slowing down tumor growth in the others. The combined data presented has important implications for using immunotherapy to treat brain tumors in patients with GBM."


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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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