HIV-Specific T Cells Generated from Naive T Cells Suppress HIV In Vitro and Recognize Wide Epitope Breadths.
Mol Ther
; 26(6): 1435-1446, 2018 06 06.
Article
em En
| MEDLINE
| ID: mdl-29724686
The Berlin Patient represents the first and only functional HIV cure achieved by hematopoietic stem cell transplant (HSCT). In subsequent efforts to replicate this result, HIV rebounded post-HSCT after withdrawal of antiretroviral therapy. Providing HIV-specific immunity through adoptive T cell therapy may prevent HIV rebound post-HSCT by eliminating newly infected cells before they can seed systemic infection. Adoptive T cell therapy has demonstrated success in boosting Epstein-Barr virus and cytomegalovirus-specific immunity post-HSCT, controlling viral reactivation. However, T cell immunotherapies to boost HIV-specific immunity have been limited by single-epitope specificity and minimal persistence or efficacy in vivo. To improve this strategy, we sought to generate allogeneic HIV-specific T cells from human leukocyte antigen (HLA)-A02+ HIV-negative adult or cord blood donors. We focused on HLA-A02+ donors due to well-characterized epitope restrictions observed in HIV+ populations. We show that multi-antigen HIV-specific T cells can be generated from naive T cells of both cord blood and adults using a reproducible good manufacturing practice (GMP)-grade protocol. This product lysed antigen-pulsed targets and suppressed active HIV in vitro. Interestingly, these cells displayed broad epitope recognition despite lacking recognition of the common HLA-A02-restricted HIV epitope Gag SL9. This first demonstration of functional multi-antigen HIV-specific T cells has implications for improving treatment of HIV through allogeneic HSCT.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T
/
HIV-1
Tipo de estudo:
Guideline
Limite:
Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article