In vivo effects of romidepsin on T-cell activation, apoptosis and function in the BCN02 HIV-1 kick&kill clinical trial
Visualitza/Obre
Cita com:
hdl:2117/344541
Tipus de documentArticle
Data publicació2020-03-20
Condicions d'accésAccés obert
Llevat que s'hi indiqui el contrari, els
continguts d'aquesta obra estan subjectes a la llicència de Creative Commons
:
Reconeixement-NoComercial-SenseObraDerivada 3.0 Espanya
Abstract
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.
Descripció
Copyright © 2020 Rosás-Umbert, Ruiz-Riol, Fernández, Marszalek, Coll, Manzardo,Cedeño, Miró, Clotet, Hanke, Moltó, Mothe, Brander and the BCN02 study group.This is an open-access article distributed under the terms of the Creative CommonsAttribution License (CC BY). The use, distribution or reproduction in other forumsis permitted, provided the original author(s) and the copyright owner(s) are creditedand that the original publication in this journal is cited, in accordance with acceptedacademic practice. No use, distribution or reproduction ispermitted which does notcomply with these terms.
CitacióRosas, M. [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", 20 Març 2020, vol. 11, p. 418-1-418-11.
ISSN1664-3224
Fitxers | Descripció | Mida | Format | Visualitza |
---|---|---|---|---|
fimmu-11-00418.pdf | 1,104Mb | Visualitza/Obre |