Engineered cells seek out and kill HIV in living organisms
By Ben Coxworth
April 13, 2012
Although there is currently no cure for HIV, the body does already contain cells that fight the virus – the problem is, there just aren’t enough of them to completely get rid of it. In 2009, scientists at UCLA performed a proof-of-concept experiment, in which they were able to grow these CD8 cytotoxic T lymphocytes (better known as infection-fighting “T cells”) from genetically engineered human stem cells. Now, in a subsequent study, they have demonstrated that these engineered cells can seek out and kill HIV-infected cells in a living organism.
In the previous project, the researchers took T cells from an HIV-infected individual, and isolated the T cell receptor within them – this is what allows the cells to identify and destroy cells infected with HIV. They proceeded to clone this receptor, then used it to genetically engineer human blood stem cells. These cells were then placed in human thymus tissue, that had itself been implanted in mice, where they proceeded to grow into HIV-specific T cells.
While the study indicated that it was possible to create genetically engineered HIV-fighting cells in the body, it didn’t test how those cells fared against HIV in a living organism. The more recent study, however, did.
This time around, similarly engineered HIV-specific T cells were introduced into infected “humanized mice” – lab mice that have been genetically engineered to carry human genes, cells or tissues. Two to six weeks later, tests were performed on the peripheral blood, plasma and organs of those mice. It was found that not only had the level of HIV in the bloodstream decreased, but the number of CD4 “helper” T cells had increased – CD4s are white blood cells that play a key role in fighting off infections, and they normally decrease in the event of HIV infection.
According to the scientists, these results indicated that the introduced T cells had developed and migrated to the organs, where they fought the HIV infection. They did note, however, that even in humanized mice, HIV may mutate slower than it does in humans. This means that multiple T cell receptors might have to be used, to account for the higher likelihood of the virus mutating in humans. To that end, the researchers have now begun creating receptors that target specific parts of the HIV virus.
"We believe that this study lays the groundwork for the potential use of this type of an approach in combating HIV infection in infected individuals, in hopes of eradicating the virus from the body," said lead investigator Scott G. Kitchen.
A paper on the study was published yesterday in the journal PLoS Pathogens.