Engineering Lifelong Cellular Immunity to HIV

A cure for HIV disease remains elusive despite much success with drug-based therapy.  We aim to develop a cure strategy for HIV infection that replaces the need of an infected individual to take expensive medications for the remainder of their life.  We seek to develop a curative stem cell-based strategy that would allow the modification of an infected individuals own immune system to better combat and attempt to control and eradicate HIV from the body in a “reverse vaccination” approach.  We are attempting to engineer an individual’s own blood-forming stem cells to allow them to safely transplant back into the body to produce immune cells that specifically target and eliminate HIV infected cells.  In these studies, we characterized and identified an optimal molecule, termed a chimeric antigen receptor (or CAR), that can be used to modify blood forming stem cells that can be transplanted into the body.  We also identified a more optimal strategy that allows the transplantation of these modified cells into the body through procedures similar to and much milder than those used in bone marrow transplantation treatments for other diseases.  When combined, this approach resulted in a safe, lifelong engraftment and production of HIV-targeting cells and in decreased amounts of virus when tested in a living system.  We are aiming to use these studies as a foundation to actively pursue the development of this therapy into the clinic and into HIV infected individual with hopes of aiding in a cure to HIV infection.