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TheBodyPRO.com covers CROI 2013

Gene Modification of Virus-Specific CD4 T Cells

Selected Research Highlight From CROI 2013

March 25, 2013

Patrick Younan from the Fred Hutchinson Cancer Research Center delivered an interesting talk about transplantation of gene-modified stem cells in pigtailed macaques (abstract, webcast -- third in session). The experiment used lentiviral vectors to deliver the gene for a virus entry inhibitor, C46 (also known as M87o, it has a similar mechanism of action to the approved antiretroviral Fuzeon), into stem cells along with a green fluorescent protein (GFP) marker to make the modified cells identifiable. Four macaques underwent stem cell transplantation, with two given C46-modified cells and two controls given cells with only the GFP marker. All were subsequently challenged with the dual-tropic SIV/HIV hybrid virus SHIV89.6P. The two controls displayed typical rapid CD4 T-cell loss, and one was euthanized at week 32 due to the onset of simian AIDS. In contrast, recipients of the modified cells recovered CD4 T-cell counts after an initial dip and showed significantly lower viral loads. Levels of gene-modified CD4 T cells peaked at around 90% during acute infection, but subsequently declined to pre-challenge levels (around 20% in one animal, 55% in the other) during follow-up. Despite the decline in modified CD4 T cells, levels of unmodified cells improved over time, suggesting a protective effect of the intervention on the overall CD4 T-cell pool.

Further studies revealed that superior SHIV-specific CD4 T-cell and antibody responses were associated with the salutary outcome. SHIV-specific CD4 T cells were not detectable in either of the controls. Younan found that a striking 85% of the SHIV-specific CD4 T cells in treated animals were gene-modified, suggesting that protection of these cells had allowed them to better perform their role of providing help to B cells and CD8 T cells. One potentially encouraging implication of this work is that gene therapy approaches might not have to protect all susceptible cells from HIV infection in order to offer benefit; if sufficient numbers of HIV-specific CD4 T cells can be protected, it is possible that these cells will do a better job of coordinating the immune response against HIV, leading to improved control of viral replication. This possibility is being investigated in ongoing trials of Sangamo BioSciences SB-728-T gene therapy, which aims to protect CD4 T cells by abrogating expression of the CCR5 coreceptor.

Richard Jefferys is the coordinator of the Michael Palm HIV Basic Science, Vaccines & Prevention Project Weblog at the Treatment Action Group (TAG). The original blog post may be viewed here.




 


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Please note: Knowledge about HIV changes rapidly. Note the date of this summary's publication, and before treating patients or employing any therapies described in these materials, verify all information independently. If you are a patient, please consult a doctor or other medical professional before acting on any of the information presented in this summary. For a complete listing of our most recent conference coverage, click here.

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