Engineering T Cells to Functionally Cure HIV-1 Infection

Mol Ther. 2015 Jul;23(7):1149-1159. doi: 10.1038/mt.2015.70. Epub 2015 Apr 21.

Abstract

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.

Publication types

  • Review

MeSH terms

  • Cell Engineering*
  • Cell- and Tissue-Based Therapy*
  • HIV Infections / therapy*
  • HIV Infections / virology
  • HIV-1 / genetics
  • HIV-1 / pathogenicity
  • Humans
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • Virus Replication / genetics