NEW YORK, Sept 30 (Reuters) -- An experimental AIDS therapy looks like a promising -- and unique -- new way to combat the virus late in the course of illness. The technique makes T cells resistant to HIV infection by blocking the production of a receptor used by HIV as a "door" to enter and kill the immune cells. Blocking this receptor essentially closes this door, making the T cells resistant to HIV infection, according to a report in Nature Medicine.
So far, the therapy has only been tested on T cells in laboratory culture dishes -- a far cry from actually treating patients. Theoretically, however, cells from an HIV-infected patient could be removed, treated, and returned to the patient to keep their immune system functioning for a longer period of time. The treated cells appear to retain at least some of their normal infection-fighting function, according to senior investigator Dr. Si-Yi Chen, an assistant professor of cancer biology at the Bowman Gray School of Medicine in Winston-Salem, North Carolina.
The new technique "should have a potent and long lasting anti-HIV effect" because the genetically manipulated immune cells could persist in the body for months or years, according to the authors.
Chen and colleagues devised the technique based on recent knowledge that HIV requires two cell receptors to attack and kill immune cells. One receptor is CD4 and the other may vary depending on the strain of HIV. Late in the course of infection, HIV often begins to use a specific receptor, called CXCR-4, to attack T cells. Some individuals are born without such receptors, making them immune or at least resistant to HIV infection.
In the new study, the researchers inserted a gene into the T cells that produced a chemokine, a compound that normally binds to the receptor when it is on the surface of a cell. Because the chemokine is inside the cell, however, this intracellular chemokine or "intrakine" binds tightly to CXCR-4, preventing it from migrating to the surface of the cell -- and keeping it out of reach of the HIV. More study is needed to determine if the therapy leaves the T cells with enough function to fight off infections, the authors noted.
However, "a strategy of genetic modification of host cells for resistance to HIV-1 infection, together with chemotherapy, may be the ultimate hope for HIV treatment," they wrote.
SOURCE: Nature Medicine (1997;3:1110-1116)
