Gene therapy wins OK to treat human disease > Should know in 6 months if it works

WASHINGTON — A federal panel approved for the first time Tuesday the treatment of human disease using gene therapy, the process of inserting curative genes into human cells.

The Recombinant DNA Advisory Committee, a panel of the National Institutes of Health, gave its approval to using gene therapy to treat a lethal form of skin cancer and an inherited disorder that deprives children of an immune system.

Approval by a committee of the Food and Drug Administration is still required before the gene therapy can begin on patients, but the NIH vote was considered the most crucial one by experts in the field.

Gerard J. McGarrity, chairman of the NIH panel, called the approval “historic.”

“What we’re doing today is adding gene therapy to vaccines, antibiotics and radiation in the medical arsenal,” said McGarrity. “Medicine has been waiting thousands of years for this.”

But Dr. Steven Rosenberg, an NIH researcher who has been experimenting in the laboratory with gene therapy for more than a decade, cautioned that the treatment “will only be important if it works. This puts us a step closer.”

Rosenberg and Dr. W. French Anderson, another NIH researcher, said they have patients, some dying of malignant melanoma, who could be used in the experimental therapy.

If successful, Anderson said, the gene therapy would be “the first step in what probably will be a revolution in medicine over the next two years.”

Rosenberg said researchers should know within six months after the treatments start whether or not the gene therapy works.

Both Rosenberg and Anderson said they expect FDA approval of their proposals soon and that they will start treating patients by this fall.

The committee’s action along with approval by the FDA will allow two groups of NIH doctors to start treating patients with cells that have been altered by the insertion of new genes.

Genes that are, in effect, instructions to a cell will cause the treated cells to produce special proteins that will either amplify a biological action or replace proteins that were missing.

Rosenberg, who proposed the anti-cancer therapy, said he plans to alter the genetic make up of a blood cell called the tumor-infiltrating lymphocyte.

This cell, called TIL, will normally seek out and attack a cancerous tumor, but it is not strong enough by itself to control the tumor.

Rosenberg earlier developed a way to remove TIL cells from a patient, culture billions of them in a test tube and then return the cells to the patient’s blood stream.

This procedure has been used in patients with malignant melanoma and about half have improved. It is the half who died that led Rosenberg to turn to gene therapy to improve the technique.

Rosenberg plans to insert into the TIL cells a gene that will command the cells to produce a protein called tumor necrosis factor, or TNF. This protein kills tumor cells by blocking them from establishing a blood supply.

In effect, the genetically altered TIL cell will be turned into a factory making a tumor-killing protein inside the tumor itself.

A slightly different technique will be used to correct a condition called severe combined immunodeficiency disease, of SCIDS.

This rare, inherited disorder occurs in children who are born lacking a key gene in a type of white blood cell called the T-lymphocyte. Without this gene, the cells cannot produce an enzyme called adenosine deaminase, or ADA. This enzyme is essential for a healthy immune system. Without it, children have no defense against disease.

Anderson, who leads the SCIDS research team, said that the plans call for T-lymphocytes to be removed from patients and cultured in test tubes. A normal gene, which will make ADA, will then be inserted into the lymphocytes, which will then be returned to the patient’s blood stream.

Once in the body, the lymphocytes will make ADA and cause the patient’s body to build resistance to disease.