Stem Cells Can Be Engineered to Kill HIV, Scientists Show

[Pint0 Xtreme]

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Stem Cells Can Be Engineered to Kill HIV, Scientists Show
ScienceDaily (Dec. 9, 2009) — 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 Researchfunded this study.

So can anyone with a much better understanding of biology and viruses in general than I do weigh in on whether this has any promise at all?

[Melchior]

The actual article: http://www.plosone.org/article/info%3Ad ... ne.0008208
As far as I can tell, the idea seems rather sound, but it could end up being not applicable in humans or useful only for a handful of rare infections for a variety of reasons (think of genetic therapy and cancer).

[Serafine666]

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So can anyone with a much better understanding of biology and viruses in general than I do weigh in on whether this has any promise at all?

It depends. Viruses, as is pretty well-known, reproduce by hijacking the genetic machinery of a cell to multiply and, by either destroying the cell itself or simply drawing the body to attack the infected cell (which is how hepatitis does its damage-the body attacks the liver cells with a virus inside). What they are describing is medically feasible; the HIV virus, after all, is known for its ability to hide from the immune system while it attacks, sometimes within the lymph nodes. Killing infected cells, however, is only part of the solution; the other side (preventing the remaining virus from infecting healthy cells can be provided by a vaccine and I recently read that they've developed one in Thailand that has shown some promise (read about it here). There is also the possibility of "training" macrophage cells (that consume infected cells; otherwise called "neutrophils") and natural killer cells (that, like the common T-cell, use a form of protein poison to trigger a cell's suicide mechanism) to target HIV-infected cells. There is also the possibility of engineering eosinophils to go after HIV-infected cells since they can either induce apoptosis or essentially strangle a cell with a reactive oxygen species and reactive nitrogen intermediates. Time will tell and this is just one more proof of the viability of stem cell research generally and non-ESC research specifically (obviously, blood stem cells are not embryonic).