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Brain Cancer Treatment

Brain cancer patients will soon join the small but growing number of people with dire diseases who may receive experimental treatment with gene therapy, according to a decision made this week by a panel of experts advising the National Institutes of Health. But the panel declined to approve a proposed gene therapy experiment involving AIDS patients until researchers can demonstrate the safety of the approach in animal tests.

The NIH Recombinant DNA Advisory Committee voted to allow a group led by Edward H. Oldfield of the National Institute of Neurological Disorders and Stroke to insert a "suicide" gene into the tumors of three patients with brain cancer. The researchers, who must also win approval from the Food and Drug Administration, expect the genes to render the tumors more vulnerable to chemotherapy.

Oldfield and his colleagues plan to use needles to inject mouse cells infected with genetically engineered viruses directly into the patients' brain tumors. The viruses will contain a gene from a herpes simplex virus that makes them susceptible to the antiviral drug ganciclovir. The researchers anticipate that the infected mouse cells will spread the engineered virus to the growing tumors, allowing subsequent ganciclovir treatment to kill the cancerous cells. On the basis of results from animal studies, they predict that the treatment will not affect healthy brain tissue, because the viruses can only infect dividing cells. Normal brain cells do not usually divide after birth.

Earlier this year, the NIH committee approved a more limited use of the suicide gene to treat ovarian cancer. This experiment, first proposed last summer (SN: 8/3/91. p.69), does not employ cells infected with live viruses. Instead, it relies on genetically engineered cells to transfer the gene to cancerous cells in a process that is not well understood.

During this week's meeting, the committee voted to defer consideration of a proposal to inject AIDS patients with genetically engineered white blood cells that might help combat HIV, the AIDS-causing virus. In the proposal, a team led by Clay Smith of the Memorial Sloan-Kettering Cancer Center in New York City sought approval to restore AIDS patients' depleted white blood cells with similar cells resistant to HIV infection.

Smith's group proposed to insert extra copies of a single HIV gene into white blood cells taken from the healthy twins of 15 AIDS patients and then to infuse these cells into the patients. During HIV infection, this gene, called TAR, must bind to a specific protein in order for HIV to reproduce all of its genes and multiply. The researchers hoped to flood the newly transplanted cells with superfluous TAR genes as a means to sop up all of these proteins and prevent HIV from infecting the new cells.

Smith and his colleagues have shown that this strategy slows the infection of white blood cells in culture dishes. But because the treatment could theoretically induce cancers or cause HIV to spread more rapidly, the committee refused to approve the proposal until the group confirms the safety and efficacy of the approach in animals.

In February, the committee approved the first gene therapy experiment for AIDS patients. It involves infusing patients with white blood cells containing a marker gene to determine whether the cells survive long enough to fight HIV.

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