Scientists at Duke University Medical Center, the University of North Carolina, and the biotech MacroGenics ($MGNX) have teamed up to design a molecule with the capacity to bind HIV-infected cells and unite them with the immune system's killer T cells.
MacroGenics' DART, or Dual-Affinity Re-Targeting protein, refers to the bimodal specific actions of the molecule. Antibodies that attach to the molecule were discovered at Duke and so far demonstrate effectiveness in targeting both the HIV-infected cell and the host's killer T cells that can then destroy and clear the infected cell.
Julia Sung, who is the lead author of the study, showed the value of DART molecules when she attached other agents to them which wake up the latent reservoirs of virus hiding in the body.
"This is an exciting approach that has the potential to clear a pool of cells that are so hard to get rid of--virus that lies silent and hidden in the host," said Dr. Barton Haynes, who is a senior author and director of the Duke Human Vaccine Institute, in a release. The results were published in the Journal of Clinical Investigation.
"These drugs would be combined with other drugs that activate expression of HIV in the cells," Haynes said. "As soon as they are awakened the DART molecules hit them and cause the killer T cells to destroy the virus."
The researchers isolated lymphocytes from a patient infected with HIV, plated the cells and reinfected them with different HIV virus subtypes and with virus that they also isolated from the patient's latent viral reservoir. They found that when the patient cells expressed these various subtypes of virus, the DART molecules quickly facilitate CD8 "killer" T cell clearance of those cells that became infected.
The DART molecules also showed promise in another model which together with latency-reversing agents showed that DART came out on top to be used as effective immunotherapeutics against latent HIV reservoirs.
"Because we are targeting a region of the virus envelope that appears in all mutations of the virus, we think it will make it much easier to be broadly utilized--at least from our laboratory data," said co-corresponding author Dr. Guido Ferrari in the release. "These DART molecules will facilitate the recognition. We are eager to see how this translates to human studies."