Dec. 9, 2009
Researchers at UCLA have demonstrated that adult stem cells that normally form blood and immune cells can be engineered to attack and kill HIV-infected cells. While exciting news, it should be kept in mind at this stage the research is still a proof-of-concept experiment done in mice; it shows that the technique is feasible at successfully destroying the virus-infected cells, but is still not ready for the clinic. The scientists took "killer" T-lymphocytes from an HIV-infected person and isolated the T-cell receptor molecule. "Killer" T-cells (CD8 cytotoxic lymphocytes) normally recognize and kill infected cells, but do not exist in high enough quantities to remove the HIV virus from an infected person. So the researchers cloned the DNA of that T-cell receptor molecule and added it to blood (hematopoietic) stem cells, genetically engineering them so that their progeny could attack HIV-infected cells. The engineered blood stem cells were placed into thymus tissue, which nurtures development of specific types of T-cells, including killer cells, and the tissue placed into mice to observe normal tissue development. The engineered blood stem cells grew into large quantities of killer T cells able to attack HIV-infected cells. The authors note that genetic engineering of human blood stem cells could be used to fight many types of viral infections. The paper is published in the journal PLOS One.
Genetically engineering blood stem cells to attack HIV, or to repel the virus and prevent infection, is a next step being worked on by several research groups. Preventing infection (or re-infection) has been tried with some success. Previously, a German team led by Gero Hutter used an adult stem cell bone marrow transplant to treat both leukemia and HIV infection in a patient. The patient received standard chemotherapy and bone marrow adult stem cell transplantation to treat his leukemia. But because the patient had AIDS, the doctors chose a very specific donor for the adult stem cells. The donor's cells lacked a molecule called CCR5; this cell-surface receptor acts as an attachment factor for the HIV virus, so the donor cells are resistant to HIV infection. Not only did the patient's leukemia go into remission, but virus was undetectable in his bloodstream for at least two years after the treatment and he no longer needed to take antiretroviral drugs. This shouldn't be considered a "cure"; the virus can hide in the body at undetectable levels, and the chemo treatment is not gentle to the system. But it does offer hope for possible future treatments based on preventing access of the virus. The peer-reviewed paper was published in the New England Journal of Medicine in 2009.