Gene Therapy Safe in Decade-Long HIV Study That May Widen Use

An experimental gene therapy given to HIV patients more than a decade ago still appears durable and safe, a new study suggests. Forty-three people were given genetically altered versions of their own T cells engineered to target an HIV protein and kill infected cells, and all but two subjects were healthy up to 11 years later.

The gene therapy field has labored under suggestions that the viruses used to transfer genes might be a leukemia risk. The field was deal a setback in 1999, when an 18-year-old died within hours of being injected with a gene therapy. Two of 10 patients acquired leukemia in an earlier French trial of a gene therapy against "Bubble Boy disease," or severe combined immunodeficiency.

Patients in the newly published research received at least one transfusion of their own cells, genetically altered to target HIV, between 1998 and 2005. The Food and Drug Administration required a follow-up of 15 years to watch for any late-developing side-effects. The patients were followed every year after the initial dose.

"We turned those cells into heat-seeking missiles directed against HIV-infected cells," said Bruce Levine, a study co-author and researcher with the University of Pennsylvania. "What really surprised us was when we got those samples, not only could we detect the gene-modified cells but they appeared to be present at relatively stable levels."

When the cells were studied in the lab, they were still able to proliferate in the presence of HIV and attack. However, the potential effectiveness beyond nine years was difficult to pinpoint due to limited samples, the study concluded.

The study, "Decade-Long Safety and Function of Retroviral-Modified Chimeric Antigen Receptor T Cells," was published in Science Translational Medicine (2012;4(132):132ra53).