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701138.pdf (1.1 MB)

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2020-03-20

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cc-by (c) Rosas-Umbert, Miriam et al., 2020
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/174258

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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Recurs relacionat

https://doi.org/10.3389/fimmu.2020.00418

Resum

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.

Matèries

Cèl·lules T, Vacunació, Apoptosi

Matèries (anglès)

T cells, Vaccination, Apoptosis

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Articles publicats en revistes (Medicina)
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)

Citació

ROSAS-UMBERT, Miriam, et al. In vivo effects of romidepsin on T-Cell activation, apoptosis and function in the BCN02 HIV-1 kick&Kill clinical trial. Frontiers in Immunology. 2020. Vol. 11, num. 418. ISSN 1664-3224. [consulted: 4 of August of 2026]. Available at: https://hdl.handle.net/2445/174258

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