HIV clinical trials Baltimore

People living with HIV will be treated with genetically engineered stem cells next month by the team of Nobel Prize-winning immunologist David Baltimore.

The goal: to create, in patients, new immune systems resistant to HIV.

“We are very hopeful we can use that as a way of effectively curing patients, and allowing them to live drug-free lives, ” Baltimore told the World Science Festival in New York on May 31.

The trial, which blends techniques both conjured in the lab and pilfered from nature, is long-awaited. Baltimore calls it a “Hail Mary Pass.” Like trials sponsored by Sangamo Biosciences, it was partly inspired by the “Berlin Patient” Timothy Brown.

A leukemia patient, Brown needed a bone marrow stem-cell transplant to replace his blood cells with those of a donor. Because he also had HIV, his doctor gave him bone marrow cells that were an immunological match, with a twist: they were from a donor who was one of the 1% of the European population resistant to HIV.

Brown’s HIV vanished. It has not returned in six years.

In a series of ongoing Sangamo trials, scientists have been disarming the gene that made Brown and the 1% resistant: the CCR5 gene coding for a receptor on CD4 T cells through which the virus enters. HIV-resistant people have two copies of the defective CCR5 gene. Sangamo has been removing patient blood cells; disarming CCR5 in their CD4 T cells (by slipping disruptive “zinc finger nucleases” (ZFNs) into their genomes via different techniques, including adenoviral vectors); returning the cells. (See related Drug Discovery and Development story here.)

Some preliminary results have been highly encouraging. But some experts say the key to long-term success may lie in altering CCR5 in stem cells, permanent cells of the bone marrow, which mature into—and give the body—a lifetime coterie of blood cells, including T cells. For that reason, many groups are now disarming CCR5 in stem cell pre-clinical work.1