HIV Molecule Becomes Cancer-Seeking Trojan Horse

Disguising a disabled HIV molecule in new attire enabled it to track down metastasized melanoma cells in living mice, according to a new study. The researchers added luciferase, the protein that makes fireflies glow, to the virus to track its movement from the bloodstream to new tumors in the mice's lungs.

"For the past 20 years, gene therapy has been hampered by the lack of a good carrier for therapeutic genes that can travel through the blood and aim itself at a precise location, thereby minimizing harmful side effects,” explained Irvin S.Y. Chen, Ph.D., director of the University of California, Los Angeles (UCLA), AIDS Institute (CA, USA). "Our approach proves that it is possible to develop an effective carrier and reprogram it to target specific cells in the body.”

The investigators used a two-step approach to convert the HIV molecule into a cancer-finding missile. They first used a type of HIV from which the viral components that cause AIDS had been taken out. This allowed the virus to infect cells and spread throughout the body without initiating disease.

"The disarmed AIDS virus acts like a Trojan horse--transporting therapeutic agents to a targeted part of the body, such as the lungs, where tumors often spread,” remarked Dr. Chen, a professor of medicine, microbiology, immunology and molecular genetics and a member of the Jonsson Comprehensive Cancer Center at the David Geffen School of Medicine at UCLA.

The second step was to strip off the HIV's viral coat and put on another coat incorporating the Sindbis virus, which typically infects insects and birds. By changing to the Sindbis coat, they reprogrammed the HIV molecule, which usually infects T cells, to track down and attach to P-lipoproteins, molecules situated on the surface of many cancer cells. The UCLA researchers are the first to validate that modified HIV will target and bind with P-gycloproteins.

"P-glycoproteins cause big problems by making the cell resistant to chemotherapy,” said Dr. Chen. "They act like soccer goalies and punt therapeutic drugs out of the cancer cell. This prevents the drug from taking effect and allows the tumor to continue growing unchecked.”

To track the molecule, the investigators injected the HIV molecule into a vein in the mouse's tail and used a special optical camera to track the movement of the luciferase. "The virus traveled through the animal's bloodstream and homed straight to the cancer cells in the lungs, where the melanoma had migrated,” said Dr. Chen.

When the investigators placed the mouse under the camera, the luciferase illuminated the cancer cells, which glowed through the mouse's bones fur, and muscles. The method is noninvasive and does not cause harm or pain to the animal. Although Dr. Chen is excited at proving that HIV can be used to target cancer cells, he cautioned that the approach must be further evaluated for specificity and safety before it can be assessed as a possible gene-based therapy for humans.
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"Our next step will be to test whether we can direct therapeutic genes to the precise location where cancer cells reside,” Dr. Chen said. "This approach offers many potential applications for controlling cancer and other diseases. We may be able to boost immune-system surveillance at tumor sites, identify cancer cells' exact location, and kill them before they cause damage,” he added. "Beyond cancer, it may be possible to correct acquired and genetic diseases where the mutations exert their harmful effects on the body.”


Related Links:
UCLA AIDS Inst