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...
| Main Authors: | , , , , , , , , , , , , , |
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| 格式: | Journal article |
| 語言: | English |
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Frontiers Media
2020
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| _version_ | 1826267489127890944 |
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| author | Rosás-Umbert, M Ruiz-Riol, M Fernández, MA Marszalek, M Coll, P Manzardo, C Cedeño, S Miró, JM Clotet, B Hanke, T Moltó, J Mothe, B Brander, C BCN02 study group |
| author_facet | Rosás-Umbert, M Ruiz-Riol, M Fernández, MA Marszalek, M Coll, P Manzardo, C Cedeño, S Miró, JM Clotet, B Hanke, T Moltó, J Mothe, B Brander, C BCN02 study group |
| author_sort | Rosás-Umbert, M |
| collection | OXFORD |
| 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. |
| first_indexed | 2024-03-06T20:54:58Z |
| format | Journal article |
| id | oxford-uuid:38e1e01c-1ab3-49f9-888e-88ef29b76411 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T20:54:58Z |
| publishDate | 2020 |
| publisher | Frontiers Media |
| record_format | dspace |
| spelling | oxford-uuid:38e1e01c-1ab3-49f9-888e-88ef29b764112022-03-26T13:52:36ZIn vivo effects of romidepsin on T-cell activation, apoptosis and function in the BCN02 HIV-1 kick&kill clinical trialJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:38e1e01c-1ab3-49f9-888e-88ef29b76411EnglishSymplectic ElementsFrontiers Media2020Rosás-Umbert, MRuiz-Riol, MFernández, MAMarszalek, MColl, PManzardo, CCedeño, SMiró, JMClotet, BHanke, TMoltó, JMothe, BBrander, CBCN02 study groupRomidepsin (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. |
| spellingShingle | Rosás-Umbert, M Ruiz-Riol, M Fernández, MA Marszalek, M Coll, P Manzardo, C Cedeño, S Miró, JM Clotet, B Hanke, T Moltó, J Mothe, B Brander, C BCN02 study group 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 |
| 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 |
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