A proof-of-principle study has demonstrated that it is possible to engineer human blood stem cells into cells that can target and kill HIV-infected cells. The result is the equivalent of a genetic vaccine which is not only good news in the fight against HIV - the process could also be used against a range of chronic viral diseases.
In the study researchers from the UCLA AIDS Institute and colleagues took the “killer” T cells that help fight infection, known as CD8 cytotoxic T lymphocytes, from an HIV-infected individual. The researchers then identified the molecule known as the T-cell receptor – the molecule that guides the T cell in recognizing and killing HIV-infected cells. Although these cells are able to destroy HIV-infected cells, they 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.
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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. And with the results of the study suggesting the strategy could be an effective weapon in the fight against AIDS, the researchers also hope to expand the range of viruses against which this approach could be used.
"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."
The study, “Engineering Antigen-Specific T Cells from Genetically Modified Human Hematopoietic Stem Cells in Immunodeficient Mice,” was published on Dec. 7 in the online journal PLoS ONE.