A novel approach to boosting the immune system's ability to attack tumors is showing promise in children suffering from advanced bone cancer, and also may be useful against other types of cancer that become resistant to traditional drugs.

The treatment -- called biological therapy, or immunotherapy -- relies on compounds that exist normally in the body, and which, in recent years, can be manufactured in the laboratory. For an increasing number of stubborn cancers, these agents are being used in combination with conventional chemotherapy or as an alternative to help patients get rid of malignant cells that have spread from the original tumor to other parts of the body.

"In the last several years, people have developed an interest in combining {the biological therapies} with more standard treatments," such as surgery and chemotherapy, said Steven A. Rosenberg of the National Cancer Institute.

At the University of Texas M.D. Anderson Cancer Center in Houston, researchers are treating 30 children who have advanced bone cancer with a new biological method that stimulates a key immune cell to wipe out wayward tumor cells. In many bone cancer patients, tiny bits of tumor escape to the lungs before the tumor is detected and surgically removed.

The escaped cancer cells have a special marker that is recognized by immune cells called macrophages, which patrol the body like garbage collectors scavenging debris and destroying dead or diseased cells. Cell biologist Isaiah Fidler and colleagues at M.D. Anderson have found a way to enhance the tumor-killing activity of these macrophages. Normally, it takes 10 to 20 macrophages to kill one cancer cell. But when millions of macrophages are in their activated state, animal experiments show, they can shrink and even eliminate tumors. Preliminary results with cancer patients suggest that the approach is safe and ultimately may be effective against different types of human cancers.

The M.D. Anderson study will not be complete for another six months, but "the initial results are very encouraging," Fidler said.

Most of the children have responded to the treatment; their tumors have shrunk or seemed to disappear after they underwent regular injections to activate the macrophages over a six-month period, according to Eugenie Kleinerman, a pediatrician at M.D. Anderson. In some children, however, tumors began growing again when treatment was discontinued.

Physicians have been actively experimenting with biological agents since the late 1970s, when the American Cancer Society committed several million dollars to test a crude preparation of the normal body protein, interferon, against several types of cancer, including those of the breast, colon, kidney and skin.

A protein produced by cells in response to a viral infection, interferon inhibits cell division -- the reason cancer researchers believed it might be useful against tumors. Interferon also activates some types of immune cells in the body, including macrophages.

But initial results were disappointing, although interferon did occasionally shrink some types of tumors, such as cancers of the breast, but it did not control the disease. Today, interferon is used to treat a majority of the patients with hairy cell leukemia, a rare form of blood cancer and is able to control the disease in 80 to 90 percent of the patients, said Stephen P. Creekmore, who oversees biological therapy research funded by NCI. It also is used experimentally in combination with other drugs for kidney cancer and one other form of leukemia.

"Interferon got us into the game," said John Laszlo, the American Cancer Society's senior vice president for research, "and it still has some very practical applications. The drug is not dead."

One form of the protein -- alpha-interferon -- in combination with other drugs is now becoming part of standard treatment for Kaposi's sarcoma, an unusual form of skin cancer that is commonly associated with AIDS.

Interleukin-2, or IL-2, is another immune stimulating compound identified about the same time as interferon. IL-2 stimulates the growth of T cells, a type of white blood cell that is central to immunity.

NCI's Rosenberg has developed a system of using interleukin-2 to mass produce cancer-fighting T cells taken from individual patients with melanoma, a deadly form of skin cancer. After billions of T cells were grown in the laboratory, they were returned to the patient in hopes that they might attack the tumor. In the most recent set of studies with some 90 patients, the treatment shrank the tumors in 40 percent of the patients and caused them to disappear completely in 10 percent.

In most of the patients with a partial response, the cancer ultimately began growing again; half of the patients in the study did not respond to the treatment and have died from their disease.

Rosenberg recently received permission from the Food and Drug Administration to use gene therapy techniques to transform T cells into a kind of genetic Trojan horse. The NCI scientists want to put a gene for tumor necrosis factor, or TNF, another biologically active compound, inside the T cells. TNF virtually melts tumors in animals but causes severe side effects in humans, thus curtailing its use in cancer patients.

The idea is that the T cells will act like delivery trucks and deposit a small, but potent amount of TNF on the cancer, killing the malignant cells but sparing the patient the side effects usually associated with the toxic compound.