Nasal Gene Therapy Effective in Treatment of Osteosarcoma Metastases to Lungs

Researchers at The University of Texas M. D. Anderson Cancer Center have shown that an intranasal gene therapy prevents the growth of osteosarcoma cells in the lungs of mice.

In a poster session at the 90th annual meeting of the American Association for Cancer Research (AACR) in mid-April, the M. D. Anderson research team showed that mice that received the new treatment had a significant reduction in the size and number of tumors that had spread to the lungs.

"In animals we have demonstrated that this new intranasal administration can effectively control lung metastases by getting the IL-12 directly to the lungs and cutting off the blood supply necessary for the growth of tumors," said Dr. Laura Worth, junior faculty associate in pediatrics at M. D. Anderson. "Though there is much more work to be done, we believe this could evolve into a novel way to treat human osteosarcoma metastases that are resistant to chemotherapy."

Osteosarcoma is a form of bone tumor that is most common in children and adolescents. Approximately 30 to 40 percent of patients with osteosarcoma will have microscopic spread of the disease to the lung, a condition that can be fatal.

For patients with osteosarcoma that has spread to the lungs, current treatment includes surgery to remove the tumor and chemotherapy to combat the metastasis to the lungs.

According to M. D. Anderson researchers, current therapy can effectively treat approximately 65 percent of all newly-diagnosed patients, a number that has stagnated for the past 10 years. Few alternatives exist for patients who do not respond to chemotherapy.

The M. D. Anderson basic science team used the new delivery system to carry directly into the lungs of mice genetic agents to stimulate production of Interleukin-12 (IL-12), a protein secreted by white blood cells which stimulates the body's immune system and inhibits the growth of blood vessels feeding the tumor. Almost all osteosarcomas have an extensive vascular system that sustains the growth and spread of tumors.

Comparing the animals that received no therapy and those treated with the adenovirus with the control gene, the mice that received the adenovirus containing the IL-12 gene had significantly fewer and smaller metastases. The lungs in the treated mice had a median number of 1.5 tumors compared with 32 tumors in the control mice.

"We believe this new form of gene therapy to be yet one more way to approach the prevention of lung metastases," said Dr. Worth.

- JULIE A. PENNE

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©2006 Texas Medical Center

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