[HTML][HTML] Engineering T cells to functionally cure HIV-1 infection

RS Leibman, JL Riley - Molecular Therapy, 2015 - cell.com
RS Leibman, JL Riley
Molecular Therapy, 2015cell.com
Despite the ability of antiretroviral therapy to minimize human immunodeficiency virus type 1
(HIV-1) replication and increase the duration and quality of patients' lives, the health
consequences and financial burden associated with the lifelong treatment regimen render a
permanent cure highly attractive. Although T cells play an important role in controlling virus
replication, they are themselves targets of HIV-mediated destruction. Direct genetic
manipulation of T cells for adoptive cellular therapies could facilitate a functional cure by …
Despite the ability of antiretroviral therapy to minimize human immunodeficiency virus type 1 (HIV-1) replication and increase the duration and quality of patients' lives, the health consequences and financial burden associated with the lifelong treatment regimen render a permanent cure highly attractive. Although T cells play an important role in controlling virus replication, they are themselves targets of HIV-mediated destruction. Direct genetic manipulation of T cells for adoptive cellular therapies could facilitate a functional cure by generating HIV-1–resistant cells, redirecting HIV-1–specific immune responses, or a combination of the two strategies. In contrast to a vaccine approach, which relies on the production and priming of HIV-1–specific lymphocytes within a patient's own body, adoptive T-cell therapy provides an opportunity to customize the therapeutic T cells prior to administration. However, at present, it is unclear how to best engineer T cells so that sustained control over HIV-1 replication can be achieved in the absence of antiretrovirals. This review focuses on T-cell gene-engineering and gene-editing strategies that have been performed in efforts to inhibit HIV-1 replication and highlights the requirements for a successful gene therapy–mediated functional cure.
cell.com