Attacking Latent HIV with convertibleCAR-T Cells, a Highly Adaptable Killing Platform

Cell. 2019 Oct 31;179(4):880-894.e10. doi: 10.1016/j.cell.2019.10.002. Epub 2019 Oct 24.


Current approaches to reducing the latent HIV reservoir entail first reactivating virus-containing cells to become visible to the immune system. A critical second step is killing these cells to reduce reservoir size. Endogenous cytotoxic T-lymphocytes (CTLs) may not be adequate because of cellular exhaustion and the evolution of CTL-resistant viruses. We have designed a universal CAR-T cell platform based on CTLs engineered to bind a variety of broadly neutralizing anti-HIV antibodies. We show that this platform, convertibleCAR-T cells, effectively kills HIV-infected, but not uninfected, CD4 T cells from blood, tonsil, or spleen and only when armed with anti-HIV antibodies. convertibleCAR-T cells also kill within 48 h more than half of the inducible reservoir found in blood of HIV-infected individuals on antiretroviral therapy. The modularity of convertibleCAR-T cell system, which allows multiplexing with several anti-HIV antibodies yielding greater breadth and control, makes it a promising tool for attacking the latent HIV reservoir.

Keywords: CAR-T; HIV latency; MicAbody; T cell therapy; bNAb; broadly neutralizing HIV antibodies; convertibleCAR-T; reduce-and-control; reservoir; shock-and-kill.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antibodies, Anti-Idiotypic / immunology
  • Antibodies, Anti-Idiotypic / pharmacology*
  • HEK293 Cells
  • HIV Infections / genetics
  • HIV Infections / immunology
  • HIV Infections / therapy*
  • HIV Infections / virology
  • HIV-1 / immunology
  • HIV-1 / pathogenicity
  • Humans
  • Immunotherapy, Adoptive*
  • Mice
  • Palatine Tonsil / immunology
  • Palatine Tonsil / metabolism
  • Primary Cell Culture
  • Spleen / immunology
  • Spleen / metabolism
  • T-Lymphocytes, Cytotoxic / immunology
  • Virus Latency / immunology
  • Virus Replication / genetics*
  • Virus Replication / immunology


  • Antibodies, Anti-Idiotypic