"The immunologic data presented at ICAAC have predictive implications for the success of this exciting new therapeutic approach to HIV and the realization of a 'functional cure' for the disease," commented Rafick-Pierre Sékaly, Ph.D., Co-Director & Chief Scientific Officer, the
"These data are very important because CD4 T-cells, especially memory T-cells, are precisely the cell type that we would want to protect and expand to enable HIV-infected individuals to control infections, and HIV, without antiretroviral drugs," added
SB-728-T is generated by ZFN-mediated modification of the gene encoding the CCR5 receptor in a patient's own T-cells, disrupting the expression of this key co-receptor for HIV entry and rendering the modified cells resistant to HIV infection.
In an oral presentation made on
Analysis of the specific types of CD4 T-cells that comprise the initial increase in CD4+ T-cells post-infusion revealed that they were primarily transitional memory T-cells (TTM). The frequency of TTM expressing CD25 (a marker that identifies activated T-cells) within the SB-728-T product correlated with the peak CD4 count post-infusion (r=0.733, p=0.0172). This suggests that replication of activated TTM SB-728-T cells post-infusion accounts for the initial peak improvement in CD4+ T-cells. As the infused cells consist of only 1-10% of total memory cells at six months post-treatment, the prolonged increase in absolute numbers of CD4+ T-cells may be accounted for by the enhanced survival and differentiation of host central memory T-cells (TCM). Specifically, while the magnitude of the increase in TTM positively correlated with the peak of CD4+ T-cells in the first weeks post-infusion (r= 0.9, p=0.083), the increase in TCM correlated with the maintenance of high CD4+ T cell counts at later time points (r= 0.9, p=0.083). Proliferation of the SB-728-T product post-infusion was sustained over the year-long period reported in the study with median modified circulating cell numbers measured to be 2.04-fold relative to input at 7 days, 0.96-fold at 6 months and 1.15-fold at 1 year post-infusion.
These preliminary data confirm the prolonged engraftment of SB-728-T, and suggest that SB-728-T has the attributes to provide sustained improvement in the CD4 memory compartment and the potential to reconstitute the immune system in immune non-responders.
"Our Phase 1 trials continue to provide valuable insight into the durability and unprecedented effects of SB-728-T treatment on immune system health in HIV-infected individuals," said
Abst.#H533: "Preferential expansion of transitional (TTM) and Central Memory(TCM) CD4 T-cells following adoptive transfer of ZFN CCR5 Modified Autologous CD4 T-cells."
Abst.#H-1581: "Digital droplet PCR (DD) qPCR allows quantiation of HIV proviral DNA in aviremic HIV+ subjects on HAART treated with ZFN CCR5 modified autologous CD4 T-cells (SB-728-T)."
The presentation will describe a new highly sensitive method developed by Sangamo scientists that enables accurate quantification of very low copy numbers of HIV DNA genomes, which may be a useful tool for evaluating interventions targeting the HIV reservoir, particularly Sangamo's approach to a 'functional cure' for the disease. For a more complete description of the technique click here
Sangamo's drug, SB-728-T, is generated by ZFN-mediated modification of the gene encoding the CCR5 receptor in a patient's own T-cells. ZFN modification disrupts the expression of this key co-receptor for HIV entry and renders cells resistant to HIV infection. The approach is based on the observation that a naturally occurring mutation in the CCR5 gene, CCR5 delta-32, provides protection from HIV infection. Individuals in whom both copies of the CCR5 gene carry the delta-32 mutation are generally not susceptible to the most common strain of HIV.
The non-employee authors of these abstracts have no financial relationship with Sangamo.
ZFP Therapeutic® is a registered trademark of
This press release may contain forward-looking statements based on Sangamo's current expectations. These forward-looking statements include, without limitation, references relating to research and development of novel ZFP TFs and ZFNs and therapeutic applications of Sangamo's ZFP technology platform for the treatment of HIV/AIDS, including a potential functional cure for HIV/AIDS, projected timing of release of SB-728-T clinical data, the expansion of clinical studies for HIV-infected individuals and the initiation of additional preclinical studies of ZFN-gene modification. Actual results may differ materially from these forward-looking statements due to a number of factors, including uncertainties relating to the initiation and completion of stages of our clinical trials, whether the clinical trials will validate and support the tolerability and efficacy of ZFNs,
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