Emory Researchers Advance Gene Therapy Studies For Metastatic Melanoma Treatment

Melanoma researchers at Emory University's Winship Cancer Center are uncovering new information about a vital cellular ingredient which they believe may direct the body's immune system to kill malignant melanoma tumor cells, the most dangerous, and potentially deadly, type of skin cancer.

If large doses of this ingredient can be delivered to melanoma tumors directly, the researchers believe it might be used to effectively treat advanced cases of melanoma.

In gene studies on melanoma tumors, Emory researchers John Ansel, M.D., and Cheryl Armstrong, M.D., have discovered that a cytokine called GM-CSF (granulocyte macrophage colony stimulating factor) directs the immune system to shift into overdrive and attack melanoma tumor cells. Cytokines are natural proteins made by all cells, both normal and malignant. A single cell produces many cytokines; some influence the cell itself (an autocine effect), while others stimulate neighboring tissue, such as immune cells, for a local effect. GM-CSF is produced naturally by some human melanoma tumors, but in amounts too small to effectively eliminate tumors.

"In mouse studies, we tried delivering GM-CSF in large doses, directly to the tumor," explains Dr. Ansel. "We grew melanoma tumor cells in culture and added the GM-CSF gene. Then we reinjected the combination back into the mouse."

It worked. The animal grew a tumor that produced an abundance of the cytokine locally. It took just five days to completely eliminate tumor cells in more than half of the mice. The other half still developed tumors, but they shrank by at least 90 percent, compared with tumors not treated with the GM-CSF gene.

"Our next step is to mimic the human condition even more closely," says Dr. Armstrong. "We are developing cell lines that will metastasize in the mouse just like you'd see in a human. Then we will inject the GM-CSF gene directly into the established tumor in the mouse to see if it

Contact: Sarah Goodwin
Emory University Health Sciences Center

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