Immunotoxin from ricin may kill cells hiding HIV

By Rachel Horton
Office of News and Publications

An immunotoxin derived from the toxin ricin targets and kills cells that act as a reservoir for HIV, researchers from UT Southwestern have discovered.

A study published online Feb. 9 in Proceedings of the National Academy of Sciences revealed that the immunotoxin destroys key cells that harbor the virus and keep it insulated from cur rent drug therapies, said Dr. Ellen Vitetta, director of the Cancer Immunobiology Center and senior co-author of the study.

"Right now, the way you treat people with HIV is to put them on these multidrug cocktails," said Dr. Vitetta. "The regimen is very effective. It's also very expensive, and it involves more than 20 pills per day. And if you stop taking the cocktail, the virus rebounds, so it's a life-long therapy."

One objective of HIV research has been to detect where the virus hides in the body, allowing it to rebound, Dr. Vitetta said.

"Research from many groups has shown that the vast majority of the latent virus hides in memory CD4+ T-cells - specialized types of white blood cells that are responsible for recall responses to virtually all vaccinations and infections," said Dr. Vitetta, who holds the Scheryle Simmons Patigian Distinguished Chair in Cancer Immunobiology.

"In this study we took cells from patients who are on highly active antiretroviral therapy - the drug cocktail known as HAART - who have no detectable virus in their blood and who are harboring this latent reservoir. We asked the question: 'If we treat those cells in the test tube with an immunotoxin which recognizes memory T cells, can we kill the latently infected cells?' The answer was 'yes.'"

Dr. Vitetta said the experiments were challenging because only about one in a 100,000 cells harbors the latent virus.

"It is hard to detect these cells in the first place," she said. "This is the first time that anyone has shown that they can actually eliminate this reservoir in patients, at least ex vivo."

Importantly, the immunotoxin did not damage memory CD8+ T-cells. These are another type of white blood cells that are very important in pre venting the resurgence of viral infections like HIV. These cells do not harbor latent virus.

"We hope to start clinical trials to test the safety of the compound here at UT Southwestern in the next two years," Dr. Vitetta said.

Other UT Southwestern researchers who worked on the study were Dr. Octavio Ramilo, associate professor of pediatrics, microbiology and in the Cancer Immunobiology Center and co-director of the study; Dr. Dolores Peterson, assistant professor of internal medicine, and Dr. Donald Sodora, assistant professor of internal medicine and microbiology.