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...
| Autores: | ; ; ; ; ; ; ; ; ; ; ; ; |
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| Tipo de documento: | Artículo |
| Estado: | Published version |
| 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 |
| Nivel de acceso: | Acceso abierto |
| Palabra clave: | Cèl·lules T Vacunació Apoptosi T cells Vaccination Apoptosis |
| _version_ | 1878739270919782400 |
|---|---|
| author | Rosas-Umbert, Miriam |
| 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 |
| author_browse | Brander, Christian Cedeño, Samandhy Clotet, Bonaventura, 1953- Coll, Pep Fernández, Marco A. Hanke, Tomás Manzardo, Christian Marszalek, Marta Miró Meda, José M. (José María), 1956- Moltó, José Mothe, Beatriz Rosas-Umbert, Miriam Ruiz-Riol, Marta |
| 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 |
| collection | Dipòsit Digital de la UB |
| 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. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | ES_be4cacfd10f7ff2ec5bb73caad402d3e |
| institution | Universidad de Barcelona |
| instname_str | Universidad de Barcelona |
| network_acronym_str | ES |
| network_name_str | España |
| oai_identifier_str | oai:diposit.ub.edu:2445/174258 |
| publishDate | 2020 |
| publishDateSort | 2020 |
| publisher | Frontiers Media |
| publisherStr | Frontiers Media |
| reponame_str | Dipòsit Digital de la UB |
| spelling | In vivo effects of romidepsin on T-Cell activation, apoptosis and function in the BCN02 HIV-1 kick&Kill clinical trial 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 Cèl·lules T Vacunació Apoptosi T cells Vaccination Apoptosis 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. Frontiers Media https://hdl.handle.net/2445/174258 |
| 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 |
| status_str | publishedVersion |
| title | 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_short | 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 |
| topic | Cèl·lules T Vacunació Apoptosi T cells Vaccination Apoptosis |
| topic_facet | Cèl·lules T Vacunació Apoptosi T cells Vaccination Apoptosis |
| url | https://hdl.handle.net/2445/174258 |