Anti-PD-L1 antibody ASC22 in combination with a histone deacetylase inhibitor chidamide as a "shock and kill" strategy for ART-free virological control: a phase II single-arm study.
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引用次数: 0
Abstract
The combination of ASC22, an anti-PD-L1 antibody potentially enhancing HIV-specific immunity and chidamide, a HIV latency reversal agent, may serve as a strategy for antiretroviral therapy-free virological control for HIV. People living with HIV, having achieved virological suppression, were enrolled to receive ASC22 and chidamide treatment in addition to their antiretroviral therapy. Participants were monitored over 24 weeks to measure changes in viral dynamics and the function of HIV-specific CD8+ T cells (NCT05129189). 15 participants completed the study. At week 8, CA HIV RNA levels showed a significant increase from baseline, and the values returned to baseline after discontinuing ASC22 and chidamide. The total HIV DNA was only transiently increased at week 4 (P = 0.014). In contrast, integrated HIV DNA did not significantly differ from baseline. Increases in the proportions of effector memory CD4+ and CD8+ T cells (TEM) were observed from baseline to week 24 (P = 0.034 and P = 0.002, respectively). The combination treatment did not succeed in enhancing the function of HIV Gag/Pol- specific CD8+ T cells. Nevertheless, at week 8, a negative correlation was identified between the proportions of HIV Gag-specific TEM cells and alterations in integrated DNA in the T cell function improved group (P = 0.042 and P = 0.034, respectively). Nine adverse events were solicited, all of which were graded 1 and resolved spontaneously. The combined treatment of ASC22 and chidamide was demonstrated to be well-tolerated and effective in activating latent HIV reservoirs. Further investigations are warranted in the context of analytic treatment interruption.
ASC22是一种抗PD-L1抗体,有可能增强艾滋病病毒的特异性免疫力,而chidamide是一种艾滋病病毒潜伏逆转剂,两者结合可作为一种策略,在抗逆转录病毒治疗的同时控制艾滋病病毒。已达到病毒学抑制的艾滋病病毒感染者在接受抗逆转录病毒疗法的同时,还接受了 ASC22 和 chidamide 治疗。对参与者进行为期 24 周的监测,以测量病毒动态变化和 HIV 特异性 CD8+ T 细胞的功能(NCT05129189)。15 名参与者完成了研究。第 8 周时,CA HIV RNA 水平较基线有显著上升,停用 ASC22 和氯达酰胺后,其值恢复至基线。在第 4 周时,HIV DNA 总量仅短暂增加(P = 0.014)。相比之下,整合 HIV DNA 与基线相比没有明显差异。从基线到第 24 周,观察到效应记忆 CD4+ 和 CD8+ T 细胞(TEM)的比例增加(P = 0.034 和 P = 0.002)。联合治疗未能成功增强 HIV Gag/Pol 特异性 CD8+ T 细胞的功能。不过,在第 8 周时,T 细胞功能改善组中 HIV Gag 特异性 TEM 细胞的比例与整合 DNA 的改变之间出现了负相关(分别为 P = 0.042 和 P = 0.034)。共征集到 9 例不良反应,所有不良反应均为 1 级,并可自行缓解。ASC22和氯达酰胺联合治疗的耐受性良好,并能有效激活潜伏的HIV储库。在分析治疗中断的情况下,有必要进行进一步研究。
期刊介绍:
Signal Transduction and Targeted Therapy is an open access journal that focuses on timely publication of cutting-edge discoveries and advancements in basic science and clinical research related to signal transduction and targeted therapy.
Scope: The journal covers research on major human diseases, including, but not limited to:
Cancer,Cardiovascular diseases,Autoimmune diseases,Nervous system diseases.