Rafi Ahmed, PhD

Reviving the Immune System

Although T cells are some of the most potent weapons of the immune system, they are also sensitive creatures.  Viruses such as HIV and hepatitis C can sustain infections partly because they lure T cells into pursuit, then push them into exhaustion.  A similar pattern has been found with some cancers, in which T cells infiltrate tumors but don't attack the tumor cells.  Rafi Ahmed and his colleagues were the first to show that during chronic viral infections, T cells are present but don't attack.  His lab later found that a molecule called PD-1 was responsible for keeping T-cells in their inactive, or exhausted state.  Removing constraints imposed by PD-1, Ahmed proposed, could revive the immune system in chronically infected patients.  Ahmed's discovery also brought new energy to cancer immunotherapy.  Several companies are now developing anticancer therapies aimed at blocking PD-1.  Based on promising clinical results, an experimental therapy for advanced melanoma based on PD-1 received "breakthrough" status from the FDA in spring 2013.