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HIV-Specific T Cells Generated from Naive T Cells Suppress HIV In Vitro and Recognize Wide Epitope Breadths.
- Source :
-
Molecular therapy : the journal of the American Society of Gene Therapy [Mol Ther] 2018 Jun 06; Vol. 26 (6), pp. 1435-1446. Date of Electronic Publication: 2018 Apr 12. - Publication Year :
- 2018
-
Abstract
- 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.<br /> (Copyright © 2018. Published by Elsevier Inc.)
Details
- Language :
- English
- ISSN :
- 1525-0024
- Volume :
- 26
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Molecular therapy : the journal of the American Society of Gene Therapy
- Publication Type :
- Academic Journal
- Accession number :
- 29724686
- Full Text :
- https://doi.org/10.1016/j.ymthe.2018.04.009