In Seattle, a group headed by Hans-Peter Kiem and Keith Jerome is taking a more futuristic approach. Using an enzyme called Zinc Finger Nuclease, they are genetically altering blood and marrow stem cells so as to disable CCR5, the doorway for infection in T cells. Researchers will modify the stem cells outside the body, so that when the cells are returned some portion of the T cells in the bloodstream will be resistant to H.I.V. infection. Over time, they hope, those cells will propagate, and the patient will slowly build an immune system that is resistant to the virus. Those patients might still have a small reservoir of H.I.V., but their bodies would be able to regulate the infection.
The largest Collaboratory, with more than twenty members, is led by David Margolis, at the University of North Carolina. Margolis, an infectious-disease expert, is targeting the reservoirs directly. The idea, which has come to be known as “shock and kill,” is to reactivate the dormant virus, unmasking the cells that carry it, so that they can be destroyed. In 2012, he published the results of a clinical trial of the drug Vorinostat, which was originally developed for blood cancers of T cells, as a shock treatment. This October, “shock and kill” was widely discussed when the Collaboratory teams convened at the N.I.H., along with hundreds of other researchers, assorted academics, and interested laypeople. Margolis and his group explored in their talk new ways to shock the virus out of dormancy.
The killing stage is more challenging, because the shocked cells carry few H.I.V. antigens, the toxic flags released by pathogenic particles and recognized by the immune system prior to attack. One approach to the killing strategy comes from an unusual type of H.I.V.-positive patient who may carry the virus for decades yet seems not to be disturbed by it. Some of these so-called “élite controllers” possess cytotoxic, or killer, T cells that attack virus-producing cells. The objective is to make every H.I.V. patient into an élite controller through “therapeutic vaccination,” enabling patients to generate killer T cells on their own.
- Jerome Groopman, Can AIDS be Cured?
The largest Collaboratory, with more than twenty members, is led by David Margolis, at the University of North Carolina. Margolis, an infectious-disease expert, is targeting the reservoirs directly. The idea, which has come to be known as “shock and kill,” is to reactivate the dormant virus, unmasking the cells that carry it, so that they can be destroyed. In 2012, he published the results of a clinical trial of the drug Vorinostat, which was originally developed for blood cancers of T cells, as a shock treatment. This October, “shock and kill” was widely discussed when the Collaboratory teams convened at the N.I.H., along with hundreds of other researchers, assorted academics, and interested laypeople. Margolis and his group explored in their talk new ways to shock the virus out of dormancy.
The killing stage is more challenging, because the shocked cells carry few H.I.V. antigens, the toxic flags released by pathogenic particles and recognized by the immune system prior to attack. One approach to the killing strategy comes from an unusual type of H.I.V.-positive patient who may carry the virus for decades yet seems not to be disturbed by it. Some of these so-called “élite controllers” possess cytotoxic, or killer, T cells that attack virus-producing cells. The objective is to make every H.I.V. patient into an élite controller through “therapeutic vaccination,” enabling patients to generate killer T cells on their own.
- Jerome Groopman, Can AIDS be Cured?
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