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Mar 07, 2011
 |  BioCentury  |  Product Development

CCR5's T cell revival

First look at human data for Sangamo's SB-728-T cell therapy to treat HIV/AIDS

Chemokine receptor 5 became a hot HIV target in the mid-1990s after researchers traced a few cases of viral resistance to a rare point mutation that prevented functional expression of the receptor. While some drug developers have wrestled with small molecule CCR5 inhibitors that could be added to the antiretroviral cocktail, Sangamo BioSciences Inc. has taken a different approach that it thinks could eliminate pills from the equation entirely.

Last week, the biotech unveiled the first human safety data for its SB-728-T, providing hints that its approach is working as expected. The autologous cell therapy is designed to replace damaged or destroyed CD4+ T cells with ones resistant to HIV infection.

Chemokine receptor 5 (CCR5; CD195) is a transmembrane receptor that is the primary co-receptor for HIV-1 entry into host cells. Instead of directly blocking the receptor itself, SB-728-T seeks to block entry of the virus by permanently disrupting the expression of CCR5 by CD4+ T cells.

The process begins with harvesting a patient's CD4+ T cells in an outpatient setting. Next, the cells are genetically modified using Sangamo's zinc finger nuclease (ZFN) technology, which introduces permanent gene disruptions at the CCR5 locus. The modified cells then are expanded and re-infused back into the patient (see BioCentury, Dec. 19, 2005).

The only approved small...

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