Nov 2, 2019

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

Cell
Eytan HerzigWarner C Greene

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.

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Mentioned in this Paper

Size
T-Lymphocyte
Virus
Spleen
Cytotoxic T-Lymphocytes
Antibodies, Neutralizing
Antiretroviral Therapy
HIV Infections
Adaptation
Blood

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