Two patients with a lethal form of skin cancer yesterday began receiving an unusual experimental treatment in which their own white blood cells were injected back into their bodies after being grown and genetically modified in the laboratory.

A 29-year-old woman and a 42-year-old man are the first cancer patients to be treated with human gene therapy, an emerging technology in which extra genes are put into body cells to either restore a function lost because of genetic damage or to give the cell some helpful new characteristic. A 4-year-old girl with an inherited immune deficiency became the first human to be treated with gene therapy in September.

In this latest case, researchers at the National Institutes of Health are trying to supercharge the patients' white blood cells with a gene that produces tumor necrosis factor, or TNF, a highly potent protein that kills cancer cells. TNF itself cannot be directly injected into the body because effective doses cause severe side effects in humans.

Instead, the researchers hope the genetically engineered white blood cells will act like molecular delivery trucks dumping tiny but concentrated doses of TNF directly on the cancer cells while sparing the rest of the body. "This is an attempt to open a new door for treating cancer patients and I am optimistic about it," said Steven A. Rosenberg, NCI's chief of surgery and leader of the team.

Rosenberg said both patients tolerated the first treatment with about 100,000 gene-altered cells and were resting comfortably in the NIH clinical center. In three to four days, they will receive another 300,000 cells, and early next week, around 1 billion, he said. The final dose has yet to be determined.

Yesterday's experiment piggybacks on previous trials in which white blood cells alone have been used to attack the cancer. In earlier experiments, the NIH team isolated white blood cells from inside the tumor, grew them in the laboratory until there were billions, and then injected all of the cells into the patient's body in hopes that they would kill the cancer. About half of the time, the patients have improved. The disease disappeared in only a few.

Rosenberg, in collaboration with W. French Anderson of the National Heart, Lung and Blood Institute, received approval to conduct the TNF experiments last year.

Although this procedure is initially designed to test the safety of the treatment in humans, Rosenberg said the patients ultimately will be receiving as many white blood cells as patients in the earlier studies. The question is whether the addition of the TNF gene will make the treatment more effective, and that, Rosenberg said, will take months to determine.

Although there had been some initial difficulty getting the gene-altered cells to produce TNF, Rosenberg said the white blood cells from these two patients now are making enough TNF to begin the experiment. Two companies, Genetic Therapy Inc. (GTI) of Gaithersburg, and Cetus Corp. of Emeryville, Calif., have been making the gene-transfer systems used in these experiments. The first study was done with the GTI material.

Meanwhile, the 4-year-old girl born with a gene defect that destroyed her immune system continues to do well, said R. Michael Blaese, also at NCI.

While her disease is very rare, affecting only a few dozen children a year, the experiment on skin cancer patients may open the use of gene therapy to thousands of Americans who suffer from the disease annually.

"She has had no side effects from the treatment and her {blood} count is normal for the first time in her life," he said.

A second immune-deficient child, an 8-year-old girl, will be started on gene therapy either later this week or next week, Blaese said. Rosenberg's team is growing and genetically altering the cells of a half-dozen other skin cancer patients who he expects to treat over the next few weeks.