Researchers at the University of Pennsylvania completed a 10-year long follow up gene therapy safety study of patients that received an engineered gene which enabled immune system T-cells to recognize the HIV virus. In three trials between 1998 and 2002, immune system T-cells from the blood of 43 HIV-positive patients were infected with an modified retrovirus carrying an engineered gene called CD3-zeta. As a result, the CD3-zeta gene, which combined parts of the natural CD3 and CD4 genes to enable it to recognize the HIV virus and turn on the T-cell's immune response, became part of the genomic DNA in the T-cells. The T-cells were then injected back into the patient's blood stream. Of the 43 patients, 41 still had detectable levels of 0.01-0.1% of modified T-cells circulating, indicating the cells proliferated as a normal part of population. Perhaps more important than the length of time the cells remained, is that none of the patients appear to have any abnormalities nor do the cells appear to behave any differently from normal T-cells.
The findings indicate this gene therapy approach with T-cell populations seems reasonably safe and could be an effective technique to treat other blood borne disorders as well as HIV infection. This is in sharp contrast to a similar gene therapy approach also run in 1998-2000 to correct a genetic disorder in children. This other study also used a retrovirus vector to deliver the gene but they placed the gene in immature blood stem cells. Four out of 11 children developed leukemia and one subsequently died. The results from this recent follow up study indicate T-cells seem to be much better behaved targets for retroviral gene therapy. This is one of several recent studies indicating somatic-cell gene therapy may be a practical and effective approach to treatment for many types of diseases.