Attacking Latent HIV with convertibleCAR-T Cells, a Highly Adaptable Killing Platform. Academic Article uri icon

Overview

abstract

  • 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.

publication date

  • October 24, 2019

Research

keywords

  • Antibodies, Anti-Idiotypic
  • HIV Infections
  • Immunotherapy, Adoptive
  • Virus Replication

Identity

PubMed Central ID

  • PMC6922308

Scopus Document Identifier

  • 85074047875

Digital Object Identifier (DOI)

  • 10.1016/j.cell.2019.10.002

PubMed ID

  • 31668804

Additional Document Info

volume

  • 179

issue

  • 4