Attacking Latent HIV with convertibleCAR-T Cells, a Highly Adaptable Killing Platform.
Cell
; 179(4): 880-894.e10, 2019 10 31.
Article
em En
| MEDLINE
| ID: mdl-31668804
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Replicação Viral
/
Infecções por HIV
/
Anticorpos Anti-Idiotípicos
/
Imunoterapia Adotiva
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Cell
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Estados Unidos