University of Pennsylvania researchers have successfully genetically engineered the immune cells of 12 HIV positive patients to resist infection, and decreased the viral loads of some patients taken off antiretroviral drug therapy (ADT) entirely—including one patient whose levels became undetectable. The Phase 1 study, which appeared in the New England Journal of Medicine, is the first published report of any gene-editing approach in humans.
“This study shows that we can safely and effectively engineer an HIV patient’s own T cells to mimic a naturally occurring resistance to the virus, infuse those engineered cells, have them persist in the body, and potentially keep viral loads at bay without the use of drugs,” says senior author Carl H. June, MD.“This reinforces our belief that modified T cells are the key that could eliminate the need for lifelong ADT and potentially lead to functionally curative approaches for HIV/AIDS.”
June and his colleagues used zinc finger nuclease (ZFN) technology to modify the T cells in the patients—a “molecular scissors,” of sorts, to mimic the CCR5-delta-32 mutation. That rare mutation provides a natural resistance to the virus in 1% of the general population. The team infused the modified cells into two cohorts of patients, all treated with single infusions—about 10 billion cells—between May 2009 and July 2012. Six were taken off antiretroviral therapy altogether for up to 12 weeks, beginning four weeks after infusion, while six remained on treatment.
Infusions were deemed safe and tolerable, the authors report, and modified T cells continued to persist in the patients when tested during follow-up visits. One week after the initial infusion, testing revealed a dramatic spike in modified T cells inside the patients’ bodies. While those cells declined over a number of weeks in the blood, the decrease of modified cells was significantly less than that of unmodified T cells during ADT treatment interruption. Read the study preview.