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DARTs-Targeting the Elimination of HIV-Infection

Sep 7, 2016 3:42:11 PM / by Stacy Matthews Branch, DVM, PhD

DART eliminates CD4+ helper T cells in HIV.Available therapies used to prevent the development of AIDS in HIV-infected individuals work by reducing the level of infection, but do not completely destroy the infection. A persistent source of HIV-infected cells remains in HIV-infected individuals despite being on long-term antiviral therapy. This causes ongoing inflammation and immune system activation, putting these individuals at risk for developing non-AIDS diseases and conditions. Given the increased risk of health with the persistent presence of HIV-infected cells, new treatment approaches are needed that will completely eliminate or kill the HIV-infected cells, removing the source (reservoir) of these cells.

The use of antibodies specific for more than one target on the infected cells is a promising candidate as a possible anti-HIV therapy. These types of antibodies (bi-specific) have already been shown to have the ability to eliminate lymphoma cells present at very low levels. Using this concept, there is another type of bi-specific antibody being studied that is designed to target the HIV envelope protein. This newer antibody type is called a dual-affinity re-targeting (DART) molecule. DART molecules used in recent studies were designed to be specific for both the HIV envelope protein and CD3 (to bring on board the help of cytotoxic T cells).

Results from studies using DART on experimental cells showed their ability to eliminate CD4+ helper T cells infected with HIV. However, this effect was dependent on the actions of CD8 T cells. When these were studied in infected CD4+ helper T cells, the DARTs were able to completely kill the HIV-infected cells, even those isolated from people on currently available antiviral therapy. Another interesting observation was that DARTs were able to cause the CD8 T cells to kill the HIV-infected CD4+ helper T cells. The next step is to find out if DARTs can achieve the same effects safely in live animal experiments.

Are you interested in cell research? At HemaCare, we offer a variety of healthy T cells, as well as HIV disease-state PBMCs for all your researching needs. Please give us a call at (877) 397-3087 or visit us online for more information.

Reference:
Sloan, Derek et al. "Targeting HIV Reservoir In Infected CD4 T Cells By Dual-Affinity Re-Targeting Molecules (Darts) That Bind HIV Envelope And Recruit Cytotoxic T Cells". PLOS Pathog 11.11 (2015): e1005233. Web. 2 Sept. 2016.

Topics: CD4, CD4+ helper T cells, cytotoxic T cells, HIV, research

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