Geron and TA Therapeutics present new data supporting utility of their small molecule telomerase activator TAT0002
Geron Corporation and TA Therapeutics, Ltd., a joint venture between Geron Corporation and the biotechnology Research Corporation of Hong Kong (BRC), announced the presentation of studies demonstrating that their small molecule telomerase activator, TAT0002, enhances the anti-viral activity of CD8 T-cells from HIV/AIDS donors against infected CD4 cells from the same donors. TA Therapeutics is exploring multiple applications for telomerase activators in chronic degenerative and infectious diseases. The company's most advanced program is HIV/AIDS, and it has selected TAT0002 as the lead development candidate for this indication.
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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