An engineered, bi-specific dual affinity re-targeting (DART) molecule may reduce detectable HIV expression in patients on antiretroviral therapy, according to a study published recently in PLOS Pathogens.
The DART molecule was engineered by researchers from MacroGenics in Rockville, Maryland, headed by Scott Koenig, MD, PhD, and Gilead Sciences in Foster City, California headed by Tomas Cihlar, PhD. The researchers published a pre-clinical data study, using blood cells isolated from patients with HIV on antiretroviral therapy.
They designed the DART molecules, MGD014, which binds to hidden HIV-infected cells to expose themselves, making them vulnerable to killer T cells. The molecule, which has two parts, first attaches to the HIV envelope protein and the second attaches to CD3. According to a prepared statement, the molecules recruit killer T cells to target HIV-infected cells expressing Env protein, which can induce killing of the HIV-infected cells.
The DART molecules were tested in both resting CD4 T cells that had been infected with wild-type HIV isolates and nonstimulated CD8 T cells from the same blood donors. The researchers noted these cells better simulated reduced levels of surface envelope protein shown on reservoir cells on patients who had HIV that were on ART as well as the envelope proteins’ resting state.
In an interview with Infectious Disease Advisor, lead researcher Dr Koenig said that “while it is very early in this research and we are looking at pre-clinical principles toward further developing this molecule, the reduction of the HIV reservoir would be important for patients. When we use this designed molecule, we have the ability for T cells in the body to be recruited and reduce HIV infected blood cells.”
1. Sloan DD, Kao Lam CY, Irrinki A, 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. 2015;11(11):e1005233 DOI:10.1371/journal.ppat.1005233