Gene therapy attacks tumor cells in mice Hopkins study boosts the immune system

November 01, 1991|By Mary Knudson

Scientists at the Johns Hopkins University have successfully treated kidney cancer in a mouse by genetically altering tumor cells to boost the mouse's own immune system.

"This is the first time that this type of gene therapy has been shown to cure an animal of an already established tumor," said Dr. Drew Pardoll, a specialist in cancer and genetics.

The scientists hope that the therapy, which is described in today's issue of Science magazine, will one day be used in human patients.

The Hopkins medical school researchers took tumor cells from a mouse and engineered them to secrete large amounts of a cancer-fighting chemical that is normally produced to fight foreign substances. The body's immune system seems not to be properly activated in cancer patients, and a small but growing group of scientists believes that boosting the body's own immune system may be one of the best and least toxic ways to treat cancer.

Most studies have tried to use gene therapy to immunize healthy animals against developing subsequent cancers, Dr. Pardoll pointed out.

Just three weeks ago, Dr. Steven A. Rosenberg, a pioneer in immune system therapy at the National Cancer Institute, made the first attempt to immunize a human patient against existing cancer. He injected 200 million live, genetically altered tumor cells into the thigh of a 46-year-old man with widespread melanoma.

Dr. Rosenberg is trying to accomplish in the human patient something very similar to what the Hopkins researchers did with mice. He inserted a gene for tumor necrosis factor, a cancer-fighting protein that occurs naturally in humans and animals, into the nucleus of the tumor cells in the hope that it will stimulate the immune system to kill cancer cells throughout the body.

Dr. Rosenberg said yesterday that he has no results from the first patient but that he also has permission from the Food and Drug Administration and a National Institutes of Health committee to treat 15 patients who have other types of cancer, using tumor cells genetically engineered to contain the gene for interleukin-2.

Interleukins are chemicals produced normally in the body by a part of the immune system known as killer T-cells. The Hopkins scientists are using interleukin-4.

In the Hopkins experiments, Paul T. Golumbeck, a researcher who works with Dr. Pardoll, said that interleukin-4 attracts white blood cells called macrophages to kill the tumor. Then killer T-cells are drawn to bind directly to the tumor cells left behind. These T-cells then circulate through the animal's bloodstream and will recognize any other similar tumor cells and kill them, he said.

The therapy should eventually be refined to work in humans, because mouse and human immune systems are alike, Dr. Pardoll said. If this therapy can be made to work in human cancer patients, it could be especially beneficial to terminally ill patients whose cancer has spread to various organs and cannot be removed surgically, the scientists said.

Hopkins researchers are collaborating with scientists at the Whitehead Institute in Cambridge, Mass., to conduct studies into which combinations of tumor-fighting interleukins work best before attempting the therapy in human patients.

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