Associate Professor Brian Lawson, Ph.D.
Antiretroviral therapy currently on the market is highly effective in the treatment of HIV, lowering viral loads and inhibiting disease progression; the problem is that these drugs do not affect dormant HIV hidden in host immune cells and, over time, are associated with significant toxicity. Therefore, how do we completely eliminate HIV, active and latent, from an infected person?
One exciting approach to achieve that goal is the use of chimeric antigen receptor (CAR) T cell immunotherapy, which gained broad recognition as a new treatment modality for certain blood cancers. CAR T cells are derived from a patient’s own cells, and are engineered to identify and kill specific target cells. These T cells are especially suited to finding and killing cells that express very low levels of target proteins. Moreover, their self-sustaining nature and ability to traffic and surveil virtually the entire host are highly beneficial aspects for controlling a chronic systemic pathogen such as HIV. Indeed, in recent unrelated cancer trials, functional CAR T cells were documented in many purported HIV sanctuary sites, including the central nervous system, the digestive tract, genital tracts, secondary lymphoid tissues, etc. CAR T cells can safely stay in humans for a surprising length of time (>16 years), and thus could be excellent and safe platforms to act as long-term anti-viral sentinels.
Associate Professor Brian Lawson, Ph.D., at The Scintillon Institute, has recently been awarded a 2-year grant from the California Institute for Regenerative Medicine (CIRM), a California initiative passed by voters in 2020, to study this CAR approach. This award allows Dr. Lawson and his team to broaden the CAR approach beyond just T cells by engineering stem cells to constitutively generate many different types of immune cells that are able to identify and neutralize the HIV virus directly as well as infected host cells. The award will provide ~$1.15 million to support his laboratory and the proposed experiments, including humanized mouse viral challenges conducted at and in collaboration with the Humanized Mouse Core Facility at UCLA.
“With an hematopoietic stem cell (HSC)-based approach and new CAR designs, we believe we can solve some of the earlier issues facing CARs and HIV, and hopefully see a durable result.”, said Lawson. “By using genetically-modified autologous HSCs, we can simultaneously instruct many different types of immune cells to attack the virus. We would like to thank CIRM and California tax payers for the funding and hope these pioneering studies will provide new insights into how to access and control the reservoir of latently HIV-infected cells and address the goal of life-long viral control without drugs.”