A 29-year-old woman and a 42-year-old man became the first people ever to receive infusions of genetically altered cells to treat their cancers yesterday, said Dr. Steven A. Rosenberg, who pioneered the gene therapy at the National Cancer Institute.
The two patients both have advanced melanoma, a skin cancer that typically spreads throughout the body and is often fatal. Neither patient had responded to other types of treatment.
They are the first of 50 patients with advanced melanoma who will receive the new gene therapy during the next year. The experimental treatment, which has drawn critics -- who are fearful of tampering with human cells -- as well as supporters, underwent lengthy review by the National Institutes of Health and the Food and Drug Administration before the test on 50 patients received approval.
Dr. Rosenberg stressed that the gene therapy treatment is in its early stage of development, but his hope is that "ultimately, it may be applied to a wide range of diseases, including cancers other than melanoma."
Yesterday morning, the two patients were given transfusions of cancer-killing cells removed from their own tumors and strengthened with a gene that produces a potent anti-tumor toxin known as tumor necrosis factor (TNF).
The cancer-killing cells are white blood cells that migrate from other parts of the body to the cancer as a part of the body's defense system. These cells invade the tumor and sometimes can recognize and destroy tumor tissue. Dr. Rosenberg has treated melanoma patients with infusions of such cells that were not enhanced by adding the TNF gene and found that the tumor stopped growing in 40 percent of the treated patients.
TNF is a protein produced by humans during bacterial infections that initiates the repair of injuries and signals the body to fight infection. It has produced powerful anti-cancer activity in mice, which can tolerate much higher doses than humans. The protein cannot be given by itself in doses high enough to kill cancer cells effectively in human patients because it causes serious side effects, including shock and body wasting.
But by genetically inserting the TNF gene directly into the cancer-killing cells in a laboratory, then growing billions of the genetically altered cells and transfusing them into the patient, scientists at the National Institutes of Health hope to bring the protein's power directly to the tumor. They hope to prevent major side effects because the protein is not circulating throughout the body.
Dr. Rosenberg said in a telephone interview yesterday that the first two recipients of the gene therapy, whom he declined to identify, had experienced no side effects so far. They will receive transfusions of the altered cells every three to four days for three weeks, he said. Then they will be evaluated to see if further treatment should be given.
It will be months and probably a year before the value of this gene therapy on melanoma patients will be known, said Dr. Rosenberg, who is an immunotherapist and chief of surgery at the National Cancer Institute. The NIH team conducting the historic trial includes Dr. R. Michael Blaese, an NCI expert on childhood immune diseases, and Dr. W. French Anderson, a scientist at the National Heart, Lung and Blood Institute who also is a pioneer in gene therapy research.