Geron and TA Therapeutics present new data supporting utility of their small molecule telomerase activator TAT0002
As HIV disease progresses, certain immune cells called CD8 cytotoxic T-cells undergo accelerated replicative senescence (cellular aging) and lose their ability to proliferate and kill HIV-infected CD4 T-cells. Previously, Dr. Rita Effros, professor of pathology and laboratory medicine and a member of the AIDS Institute at the David Geffen School of Medicine at UCLA, and colleagues demonstrated that introducing the telomerase gene into CD8 cells from HIV/AIDS donors increased: 1) their proliferative capacity, 2) their ability to produce IFNã, and 3) their ability to inhibit virus production and kill HIV-infected T-cells. Dr. Effros' team also showed that Geron's small molecule telomerase activators had similar activity enhancing the ability of certain HIV-specific CD8 T-cells to inhibit virus production when co-cultured with an HLA-matched HIV-infected CD4 T-cell line.
The current work examined the effects of TAT0002 in an autologous "co-culture" setting with T-cells from three independent HIV-positive donors. In this study, CD8 and CD4 T-cells from each donor were separately expanded for 14 days with or without TAT0002. The CD8 and HIV-infected CD4 T-cells from each patient were then cultured together for 10 days at different CD8:CD4 ratios, with or without TAT0002. Virus level was measured by a standard assay. The presence of TAT0002 during the expansion and co-culture periods significantly reduced the mean virus levels for all three donors relative to the vehicle-control treated cells (p=0.003, 0.01 and 0.04 at each of three CD8:CD4 culture ratios). The level of the effect (2-5 fold reduction in virus levels) in this relatively short-term autologous study was greater than that seen previously with the HIV-infected CD4 T-cell line.
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