Profiles

Jerome Zack, Ph.D., holds the M. Philip Davis Chair in Microbiology and Immunology. The Zack laboratory at UCLA is exploring ways to purge HIV reservoirs to effect either a cure or “functional cure” (long term remission) of HIV disease. It is long lived latent reservoirs that mandate that HIV infected individuals remain on antiretroviral therapy, because upon cessation of therapy, latent reservoirs rekindle virus replication and disease progression. The Zack laboratory is exploring “kick and kill” and immune system engineering to accomplish their goals.

The kick and kill approach involves activation of infected cells to allow visualization of viral proteins, while the individual is on therapy to prevent spread of virus. Subsequently an anti-viral targeting approach is added, to kill the previously latently infected cell, which is now expressing viral proteins. Targeting approaches being pursued include cell-based effectors such as engineered CTL or NK cells. A recent study along these lines showed that a PKC modulator (kick) coupled with NK cells as the “kill” component, could decrease HIV reservoirs in a humanized mouse model.

The genetic engineering approach involves introduction of anti-HIV chimeric antigen receptors (CARs) into human hematopoietic progenitor cells. These cells then develop into effector cells in vivo (T and NK cells), which can now target HIV infected cells. This approach has shown some efficacy in humanized mice and non-human primates.

Much of Dr. Zack’s work involves the use of humanized mice, a tool which can be extended to other viral systems.