UCLA researchers demonstrate that stem cells can be engineered to kill HIV
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against lots of viruses and pathogens.
http://newsroom.ucla.edu/portal/ucla/ucla-researchers-demonstrate-that-149694.aspx
UCLA researchers demonstrate that stem cells can be engineered to kill HIV
Innovative strategy could be effective against other chronic viral diseases
By Enrique Rivero December 07, 2009 Category: Health Sciences, Research
Researchers from the UCLA AIDS Institute and colleagues have for the first time demonstrated that
human blood stem cells can be engineered into cells that can target and kill HIV-infected cells - a
process that potentially could be used against a range of chronic viral diseases.
The study, published Dec. 7 in the-peer reviewed online journal PLoS ONE, provides
proof-of-principle - that is, a demonstration of feasibility - that human stem cells can be
engineered into the equivalent of a genetic vaccine.
"We have demonstrated in this proof-of-principle study that this type of approach can be used to
engineer the human immune system, particularly the T-cell response, to specifically target
HIV-infected cells," said lead investigator Scott G. Kitchen, assistant professor of medicine in the
division of hematology and oncology at the David Geffen School of Medicine at UCLA and a member of
the UCLA AIDS Institute. "These studies lay the foundation for further therapeutic development that
involves restoring damaged or defective immune responses toward a variety of viruses that cause
chronic disease, or even different types of tumors."
Taking CD8 cytotoxic T lymphocytes - the "killer" T cells that help fight infection - from an
HIV-infected individual, the researchers identified the molecule known as the T-cell receptor, which
guides the T cell in recognizing and killing HIV-infected cells. These cells, while able to destroy
HIV-infected cells, do not exist in enough quantities to clear the virus from the body. So the
researchers cloned the receptor and genetically engineered human blood stem cells, then placed the
stem cells into human thymus tissue that had been implanted in mice, allowing them to study the
reaction in a living organism.
The engineered stem cells developed into a large population of mature, multifunctional HIV-specific
CD8 cells that could specifically target cells containing HIV proteins. The researchers also found
that HIV-specific T-cell receptors have to be matched to an individual in much the same way that an
organ is matched to a transplant patient.
The next step is to test this strategy in a more advanced model to determine if it would work in the
human body, said co-author Jerome A. Zack, UCLA professor of medicine in the division of hematology
and oncology and associate director of the UCLA AIDS Institute. The researchers also hope to expand
the range of viruses against which this approach could be used.
But the results of the study suggest that this strategy could be an effective weapon in the fight
against AIDS and other viral diseases.
"This approach could be used to combat a variety of chronic viral diseases," said Zack, who is also
a professor of microbiology, immunology and molecular genetics. "It's like a genetic vaccine."
In addition to Kitchen and Zack, investigators included Michael Bennett, Zoran Galic, Joanne Kim,
Qing Xu, Alan Young, Alexis Lieberman, Hwee Ng and Otto Yang, all of UCLA, and Aviva Joseph and
Harris Goldstein of the Albert Einstein College of Medicine in New York.
The California Institute for Regenerative Medicine (CIRM) and the UCLA Center for AIDS Research
funded this study.
The UCLA AIDS Institute, established in 1992, is a multidisciplinary think tank drawing on the
skills of top-flight researchers in the worldwide fight against HIV and AIDS, the first cases of
which were reported in 1981 by UCLA physicians. Institute members include researchers in virology
and immunology, genetics, cancer, neurology, ophthalmology, epidemiology, social science, public
health, nursing, and disease prevention. Their findings have led to advances in treating HIV, as
well as other diseases, such as hepatitis B and C, influenza and cancer.
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