Altered HIV attacks mice tumors

Researchers at the University of California at Los Angeles have tweaked HIV to create a gene therapy that attacks cancer tumors in mice.

The research is a step forward for the beleaguered field of gene therapy, which has enjoyed isolated successes and suffered repeated setbacks over the past 20 years. But tinkering and fine tuning will be the key to a successful gene therapy, UCLA researchers believe. They published their study in the Feb. 13 issue of Nature Medicine.

The UCLA AIDS Institute scientists genetically altered HIV and folded it into an envelope made of another virus called sindbis, which typically infects insects and birds. That turned the altered HIV into a missile that hunted down metastasized melanoma cells in the lungs of living mice.

"People might wonder if it's scary to use HIV as a therapy," said Irving Chen, who led the UCLA team. "But in actuality we have completely removed 80 percent of the virus. So really it's just a carrier."

Other researchers have tried morphing HIV into a gene therapy, with limited results.

"This hasn't been possible before," Chen said. "Usually (researchers) take a virus and try to modify its own envelope, but it falls off or becomes so deformed it is not able to infect cells anymore."

The secret to the UCLA researchers' success was adding the sindbis cloak, Chen said. He and his colleagues suspected the virus might make an HIV gene therapy more stable, and the results of the study showed they were right.

The scientists also inserted a glowing firefly protein into the virus to track its progress. They used a light-detection "cooled charged-coupled device," or CCCD, camera to look at the glowing protein inside live mice. Because the protein was attached to the gene therapy, the researchers could see that the treatment had hit its mark.

The researchers programmed the altered virus package to attack a protein on the cancer cell surface called p-glycoprotein, which causes problems in cancer patients by shuttling cancer drugs away from the cell. In other words, p-glycoprotein causes resistance to cancer medication. Scientists could customize the system to target any protein on the surface of a cell, Chen said. He and his colleagues have seen success with about a dozen different molecules, including brain and other blood cells, he said.

More incremental work, with the goal of increasing the precision of the treatment and reducing the chance of side effects, is necessary before this type of gene therapy can be tested in humans, Chen said. In a premature human trial in 1999, 18-year-old Jesse Gelsinger died during a gene therapy clinical trial at the University of Pennsylvania, which led to an FDA investigation and closure of the Penn gene therapy program.

"I think one of the problems with gene therapy has been whenever people get a new approach they immediately go into patients," Chen said. "Our approach has been test in cell culture, then in mice. We're not planning any clinical trials until this is fully refined."

Kristen Philipkoski

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