But two reports last week in the Proceedings of the National Academy of Sciences may bring back the excitement to gene therapy, with promising developments in the treatment of cancer and AIDS.
In one experiment, scientists from the University of California, Los Angeles, combined genetic engineering and standard vaccine therapy to destroy, apparently permanently, a pernicious type of brain tumor in rats. Led by molecular biologist Habib Fakhrai, the researchers took cells from a lab culture of a cancer called 9L gliosarcoma. They introduced them into the brains of healthy rats, where the malignant cells multiplied. Then Fakhrai’s team genetically altered some of the other cultured cancer cells by blocking a gene that makes a protein called TGF-beta. In this cancer, and in some human cancers, TGF-beta plays a nasty trick on the immune system by deactivating T-cells, which kill invaders. Shielded from attack by the immune system, the cancer spreads with impunity. But when the researchers placed the altered tumor cells in the rats’ brains, not only were the genetically engineered tumor cells destroyed by the immune system, so were all the untreated cancer cells. Twelve weeks after the experiment, all 11 rats that had received the genetically altered cells were alive and healthy, and all five control rats were dead. Even after the survivors were reinjected with more malignant tumor cells, they still beat the disease. By using genetic intervention to engage the immune system, says Fakhrai, “you’re boosting the body’s own defenses, and usually they’re much more potent than anything else we could do.” Human tumors that produce TGF-beta and might be fought this way include those of the brain, breast, colon and prostate. The researchers hope to begin preliminary human testing this summer.
Another gene-therapy experiment reported last week offered an intriguing new approach to the treatment of AIDS. Biochemist Dr. Gary Nabel and his team at the University of Michigan Medical Center took blood from two HIV-positive patients and isolated their infection-fighting T-cells. Then they inserted an HIV gene that had been modified to inhibit replication of the virus. When they marked the altered T-cells and placed them back in the patients (through transfusion), the cells survived in their bodies four to five times longer than the subjects’ untreated T-cells. “This is one critical step,” Nabel says, “to exploring other genetic therapies.” And perhaps to prolonging the lives of T-cells long enough to prolong AIDS patients’ lives.
An experiment using genetically altered cancer cells may point the way toward developing against some cancers.
Researchers inject lab-grown cancer cells into rats’ brains, where they reproduce and grow into a tumor.
Leftover cancer cells are reprogrammed so they cannot make TGF-B, a protein that shields them from the immune system.
The cells, now irradiated so they no longer reproduce, go into the rats, whose immune systems respond by destroying the cancer.
Even after reinfection with 3,000 times a fatal dose of cancer cells, the rats remain healthy. The vaccine is a success.
