In vivo effects of romidepsin on T-Cell activation, apoptosis and function in the BCN02 HIV-1 kick&Kill clinical trial

Romidepsin (RMD) is a well-characterized histone deacetylase inhibitor approved for the treatment of cutaneous T-cell lymphoma. in vitro and in vivo studies have demonstrated that it is able to induce HIV-1 gene expression in latently infected CD4+ T cells from HIV-1+ individuals on suppressive anti...

Descripción completa

Detalles Bibliográficos
Autores: Rosas-Umbert, Miriam, Ruiz-Riol, Marta, Fernández, Marco A., Marszalek, Marta, Coll, Pep, Manzardo, Christian, Cedeño, Samandhy, Miró Meda, José M. (José María), 1956-, Clotet, Bonaventura, 1953-, Hanke, Tomás, Moltó, José, Mothe, Beatriz, Brander, Christian
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/174258
Acceso en línea:https://hdl.handle.net/2445/174258
Access Level:acceso abierto
Palabra clave:Cèl·lules T
Vacunació
Apoptosi
T cells
Vaccination
Apoptosis
id ES_be4cacfd10f7ff2ec5bb73caad402d3e
oai_identifier_str oai:diposit.ub.edu:2445/174258
network_acronym_str ES
network_name_str España
repository_id_str
spelling In vivo effects of romidepsin on T-Cell activation, apoptosis and function in the BCN02 HIV-1 kick&Kill clinical trialRosas-Umbert, MiriamRuiz-Riol, MartaFernández, Marco A.Marszalek, MartaColl, PepManzardo, ChristianCedeño, SamandhyMiró Meda, José M. (José María), 1956-Clotet, Bonaventura, 1953-Hanke, TomásMoltó, JoséMothe, BeatrizBrander, ChristianCèl·lules TVacunacióApoptosiT cellsVaccinationApoptosisRomidepsin (RMD) is a well-characterized histone deacetylase inhibitor approved for the treatment of cutaneous T-cell lymphoma. in vitro and in vivo studies have demonstrated that it is able to induce HIV-1 gene expression in latently infected CD4+ T cells from HIV-1+ individuals on suppressive antiretroviral therapy. However, in vitro experiments suggested that RMD could also impair T-cell functionality, particularly of activated T cells. Thus, the usefulness of RMD in HIV-1 kick&kill strategies, that aim to enhance the immune system elimination of infected cells after inducing HIV-1 viral reactivation, may be limited. In order to address whether the in vitro observations are replicated in vivo, we determined the effects of RMD on the total and HIV-1-specific T-cell populations in longitudinal samples from the BCN02 kick&kill clinical trial (NCT02616874). BCN02 was a proof-of-concept study in 15 early treated HIV-1+ individuals that combined MVA.HIVconsv vaccination with three weekly infusions of RMD given as a latency reversing agent. Our results show that RMD induced a transient increase in the frequency of apoptotic T cells and an enhanced activation of vaccine-induced T cells. Although RMD reduced the number of vaccine-elicited T cells secreting multiple cytokines, viral suppressive capacity of CD8+ T cells was preserved over the RMD treatment. These observations have important implications for the design of effective kick&kill strategies for the HIV-1 cure.Frontiers Media2020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/174258Articles publicats en revistes (Medicina)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.3389/fimmu.2020.00418Frontiers in Immunology, 2020, vol. 11, num. 418https://doi.org/10.3389/fimmu.2020.00418info:eu-repo/grantAgreement/EC/H2020/681137cc-by (c) Rosas-Umbert, Miriam et al., 2020http://creativecommons.org/licenses/by/3.0/esinfo:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1742582026-05-27T06:46:51Z
dc.title.none.fl_str_mv In vivo effects of romidepsin on T-Cell activation, apoptosis and function in the BCN02 HIV-1 kick&Kill clinical trial
title In vivo effects of romidepsin on T-Cell activation, apoptosis and function in the BCN02 HIV-1 kick&Kill clinical trial
spellingShingle In vivo effects of romidepsin on T-Cell activation, apoptosis and function in the BCN02 HIV-1 kick&Kill clinical trial
Rosas-Umbert, Miriam
Cèl·lules T
Vacunació
Apoptosi
T cells
Vaccination
Apoptosis
title_short In vivo effects of romidepsin on T-Cell activation, apoptosis and function in the BCN02 HIV-1 kick&Kill clinical trial
title_full In vivo effects of romidepsin on T-Cell activation, apoptosis and function in the BCN02 HIV-1 kick&Kill clinical trial
title_fullStr In vivo effects of romidepsin on T-Cell activation, apoptosis and function in the BCN02 HIV-1 kick&Kill clinical trial
title_full_unstemmed In vivo effects of romidepsin on T-Cell activation, apoptosis and function in the BCN02 HIV-1 kick&Kill clinical trial
title_sort In vivo effects of romidepsin on T-Cell activation, apoptosis and function in the BCN02 HIV-1 kick&Kill clinical trial
dc.creator.none.fl_str_mv Rosas-Umbert, Miriam
Ruiz-Riol, Marta
Fernández, Marco A.
Marszalek, Marta
Coll, Pep
Manzardo, Christian
Cedeño, Samandhy
Miró Meda, José M. (José María), 1956-
Clotet, Bonaventura, 1953-
Hanke, Tomás
Moltó, José
Mothe, Beatriz
Brander, Christian
author Rosas-Umbert, Miriam
author_facet Rosas-Umbert, Miriam
Ruiz-Riol, Marta
Fernández, Marco A.
Marszalek, Marta
Coll, Pep
Manzardo, Christian
Cedeño, Samandhy
Miró Meda, José M. (José María), 1956-
Clotet, Bonaventura, 1953-
Hanke, Tomás
Moltó, José
Mothe, Beatriz
Brander, Christian
author_role author
author2 Ruiz-Riol, Marta
Fernández, Marco A.
Marszalek, Marta
Coll, Pep
Manzardo, Christian
Cedeño, Samandhy
Miró Meda, José M. (José María), 1956-
Clotet, Bonaventura, 1953-
Hanke, Tomás
Moltó, José
Mothe, Beatriz
Brander, Christian
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Cèl·lules T
Vacunació
Apoptosi
T cells
Vaccination
Apoptosis
topic Cèl·lules T
Vacunació
Apoptosi
T cells
Vaccination
Apoptosis
description Romidepsin (RMD) is a well-characterized histone deacetylase inhibitor approved for the treatment of cutaneous T-cell lymphoma. in vitro and in vivo studies have demonstrated that it is able to induce HIV-1 gene expression in latently infected CD4+ T cells from HIV-1+ individuals on suppressive antiretroviral therapy. However, in vitro experiments suggested that RMD could also impair T-cell functionality, particularly of activated T cells. Thus, the usefulness of RMD in HIV-1 kick&kill strategies, that aim to enhance the immune system elimination of infected cells after inducing HIV-1 viral reactivation, may be limited. In order to address whether the in vitro observations are replicated in vivo, we determined the effects of RMD on the total and HIV-1-specific T-cell populations in longitudinal samples from the BCN02 kick&kill clinical trial (NCT02616874). BCN02 was a proof-of-concept study in 15 early treated HIV-1+ individuals that combined MVA.HIVconsv vaccination with three weekly infusions of RMD given as a latency reversing agent. Our results show that RMD induced a transient increase in the frequency of apoptotic T cells and an enhanced activation of vaccine-induced T cells. Although RMD reduced the number of vaccine-elicited T cells secreting multiple cytokines, viral suppressive capacity of CD8+ T cells was preserved over the RMD treatment. These observations have important implications for the design of effective kick&kill strategies for the HIV-1 cure.
publishDate 2020
dc.date.none.fl_str_mv 2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/174258
url https://hdl.handle.net/2445/174258
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.3389/fimmu.2020.00418
Frontiers in Immunology, 2020, vol. 11, num. 418
https://doi.org/10.3389/fimmu.2020.00418
info:eu-repo/grantAgreement/EC/H2020/681137
dc.rights.none.fl_str_mv cc-by (c) Rosas-Umbert, Miriam et al., 2020
http://creativecommons.org/licenses/by/3.0/es
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Rosas-Umbert, Miriam et al., 2020
http://creativecommons.org/licenses/by/3.0/es
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
dc.source.none.fl_str_mv Articles publicats en revistes (Medicina)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869418274827010048
score 15.300719

Similares en LA Referencia