Modification to Deliver Interleukin 12 Directly Into Resistant Type of Brain Tumor

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EMBARGOED UNTIL FRIDAY, DEC. 28, 2001

The administration of Interleukin 12 (IL-12) has been shown in previous animal studies to be an effective therapy in treating cancer. But while this cytokine plays a key role in enabling the immune system's T-cells to attack cancer cells, systemic administration can cause harmful changes in blood and tissues, and other life-threatening side effects.

To take advantage of IL-12's benefits without risking the negative consequences, researchers seek IL-12 delivery methods that will attack cancer cells at the site of a tumor.

In an article appearing in the Dec. 28, 2001, issue of Cancer Gene Therapy, physicians and scientists at Cedars-Sinai's Maxine Dunitz Neurosurgical Institute describe an approach that "significantly prolonged" survival in mice with glioma -- an extremely deadly type of brain cancer that is highly resistant to treatment.

In the study, IL-12 was attached to an adenovirus and administered directly into tumors of the right corpus striatum of the brain. Mice receiving the genetically modified virus survived longer than those that received an adenovirus alone and those that were given normal saline solution. According to the paper's senior author, John S. Yu, M.D., IL-12 also improved the immune system's ability to infiltrate and kill tumor cells.

"Interleukin 12 is known to enhance T-helper type 1 anti-tumor immune responses," said Dr. Yu. "In our study, survival was significantly prolonged in mice that received IL-12, we had laboratory evidence of robust CD4 and CD8 T-cell infiltration of tumors, and glioma-infiltrating T lymphocytes demonstrated increased tumor-killing ability. We postulate that these findings are the result of localized induction of tumor immunity."

The study was supported in part by National Institutes of Health grant NS02232. It was conducted by researchers affiliated with Cedars-Sinai's Maxine Dunitz Neurosurgical Institute, the medical center's Department of Neurological Surgery, the University of California at Los Angeles, and the Department of Molecular Biology and Biochemistry at the University of California at Irvine.

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