Cells from a middle-age man with terminal cancer are being genetically altered at the National Institutes of Health in preparation for the first use of gene therapy in the treatment of cancer.
An NIH team led by Dr. Steven A. Rosenberg received approval Tuesday from the Food and Drug Administration to use the experimental gene therapy in patients critically ill with advanced melanoma, a deadly skin cancer.Rosenberg said his team had been poised for the approval and had already been culturing cells from the first patient's tumors.
"Now that we've got approval, we will go full speed ahead," he said.
The still-experimental therapy amplifies the body's own cancer-fighting ability. It uses a type of white blood cells, called tumor-infiltrating lymphocytes, or TIL, which naturally invade and attack tumor tissue. A gene inserted into the TIL cell adds a second natural anti-cancer protein.
In the new therapy, TIL cells are removed from a patient's tumor and placed into a culture. The scientists then add to the TIL cells two new genes, one of which makes a powerful cancer fighter called tumor necrosis factor, or TNF. The cells are further cultured until they number in the billions and then are returned to the patient's blood stream.
The TIL cells, now carrying the TNF gene, migrate back to the tumor sites. Doctors hope the treatment will bring powerful doses of the natural tumor fighters directly against cells in the melanoma tumors.
Rosenberg said the first patient to receive the therapy will be a middle-aged man who is in an advanced stage of melanoma with only weeks to live. Two other patients are standing by and culturing of their cells should start soon. He declined to further identify the patients.
The FDA gave the Rosenberg team permission to treat up to 50 melanoma patients using the new gene technique. Once the process is started, the NIH scientists expect to add about one patient a week to the treatment group.
"These are all patients with very limited life expectancy - about three months," Rosenberg said.
Rosenberg, Dr. R. Michael Blaese and Dr. W. French Anderson have been seeking approval for more than a year to use the gene therapy on patients. The technique was considered by six committees organized by the NIH before the FDA approved it for limited use.
Another form of gene therapy was approved Sept. 14 for the treatment of an extremely rare inherited immune system disorder called adenosine deaminase deficiency disease. That study's first patient, a 4-year-old girl, received a transfusion of her own white blood cells after a gene to correct the disorder had been inserted into the cells.
Rosenberg has been using unaltered TIL cells to treat melanoma since 1987. But he said the cells seemed to help only about half of the patients, and the rest died of the disease.
To strengthen the treatment, Rosenberg and his team turned to genetic engineering techniques.