Envelope-specific antibodies and antibody-derived molecules for treating and curing HIV infection

Nat Rev Drug Discov. 2016 Dec;15(12):823-834. doi: 10.1038/nrd.2016.173. Epub 2016 Oct 7.

Abstract

HIV-1 is a retrovirus that integrates into host chromatin and can remain transcriptionally quiescent in a pool of immune cells. This characteristic enables HIV-1 to evade both host immune responses and antiretroviral drugs, leading to persistent infection. Upon reactivation of proviral gene expression, HIV-1 envelope (HIV-1 Env) glycoproteins are expressed on the cell surface, transforming latently infected cells into targets for HIV-1 Env-specific monoclonal antibodies (mAbs), which can engage immune effector cells to kill productively infected CD4+ T cells and thus limit the spread of progeny virus. Recent innovations in antibody engineering have resulted in novel immunotherapeutics such as bispecific dual-affinity re-targeting (DART) molecules and other bi- and trispecific antibody designs that can recognize HIV-1 Env and recruit cytotoxic effector cells to kill CD4+ T cells latently infected with HIV-1. Here, we review these immunotherapies, which are designed with the goal of curing HIV-1 infection.

Publication types

  • Review

MeSH terms

  • AIDS Vaccines / immunology*
  • Animals
  • Antibodies, Monoclonal / immunology
  • Antibody Specificity
  • HIV Antibodies / immunology
  • HIV Antibodies / therapeutic use*
  • HIV Infections / immunology
  • HIV Infections / therapy*
  • HIV-1 / immunology*
  • Humans
  • Immunotherapy
  • env Gene Products, Human Immunodeficiency Virus / immunology*

Substances

  • AIDS Vaccines
  • Antibodies, Monoclonal
  • HIV Antibodies
  • env Gene Products, Human Immunodeficiency Virus