Chimeric Antigen Receptor-Modified Immune Cells for Eradication of HIV Reservoirs

Abstract Host immune surveillance can achieve powerful clearance of infectious pathogens. Acute human immunodeficiency virus type I (HIV-1) infection can establish viral reservoirs in humans, and persistent chronic activation by the virus exhausts the immune system and ultimately causes acquired immunodeficiency syndrome. Although antiretroviral therapy (ART) can reduce the viral load and viremia in patients, latent HIV-1 reservoirs are still the biggest challenge that needs to be overcome to eradicate the virus. However, the low or absent viral antigen expression and epitope mutation caused during durable ART result in host immune escape and reservoir cell inaccessibility. In addition, durable ART accompanied by inflammation and persistent activation of immune cells, especially dysfunction and/or exhaustion of T cells. With the development of immunology, genetics, and genetic engineering technology, researchers can construct chimeric antigen receptors (CARs) to modify immune cells to enhance HIV clearance. The important research goals of creating CARs to modify natural killer (NK) and T cells are an attempt to enhance the functional effects of immune cells and restore the function of the immune system. This article reviews the latent characteristics of HIV, the development of CAR molecules, and the strategies for reprogramming T cells and NK cells with CARs, and aims to clear the HIV reservoirs and related potential problems.