Los Angeles Times - December 30, 2002
Jane E. Allen, Times Staff Writer

One approach, developed at Caltech in Pasadena and at UCLA, uses gene therapy to keep the AIDS virus from entering human disease-fighting cells. The other approach, from French researchers, uses a therapeutic vaccine to lower the amount of virus while boosting the immune system.

Dr. Kenneth Mayer, a national authority on AIDS and director of the Brown University AIDS Program in Providence, R.I., called both approaches exciting for HIV therapy and, potentially, prevention.

HIV, the virus that causes AIDS, is a powerful and insidious foe because it disrupts the immune system, Mayer said. The two experimental techniques represent "attempts to hijack the immune system in positive ways. Both have a long way to go, but neither one is something that is currently being done."

Both techniques might be used in combination with existing antiviral drugs to eliminate HIV from the body or keep it at bay, he said.

The gene therapy work was led by David Baltimore, a Nobel laureate biologist and president of Caltech, who collaborated with Irvin S.Y. Chen, director of the UCLA AIDS Institute. Using a technique they compared to a Trojan horse, the researchers invaded T-cells (human immune cells) with a harmless AIDS virus. The disabled virus then unleashed a piece of synthetic genetic coding it had carried inside. The genetic coding knocked out a receptor on the cell's surface, essentially locking one door HIV uses to enter cells.

Early results in a laboratory dish found the technique protected more than 80% of T-cells from HIV infection, according to the research published last week in the Proceedings of the National Academy of Sciences.

In the French research, reported in the January issue of Nature Medicine but made available online last week, lead researcher Wei Lu of the Universite Rene Descartes in Paris and his colleagues created a vaccine by treating immune cells in monkeys with an AIDS-like virus altered so it couldn't reproduce. The researchers used dendritic cells, a type of immune cells found in monkeys and humans. The cells can migrate from mucus membranes, where HIV infections begin, into lymph nodes.

When 10 macaque monkeys were vaccinated with cultures of their treated cells, then given four booster shots in eight weeks, virus levels dropped in the blood of seven monkeys.

Their viral levels stayed low over the next 34 weeks, the authors wrote, but it remained unclear how long the effects will last. In the remaining three monkeys, the virus started to increase after the first immunization.

"If the approach is confirmed in monkeys and successfully adapted in humans, it may represent a major new therapeutic approach," Dr. Bruce D. Walker, director of the Division of AIDS at Harvard Medical School, said in an accompanying Nature Medicine commentary.

The Caltech-UCLA work was supported by the National Institute of Allergy and Infectious Diseases and the Damon Runyon-Walter Winchell Fellowship. The French research was supported by the Institute for Research Into Vaccines and AIDS and Cancer Immunotherapy.
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