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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
Signal Transduction and Targeted Therapy ( IF 40.8 ) Pub Date : 2024-09-09 , DOI: 10.1038/s41392-024-01943-9
Luling Wu 1, 2 , Zhihang Zheng 1, 3 , Jingna Xun 1, 4 , Li Liu 1 , Jiangrong Wang 1 , Xinyu Zhang 1 , Yueming Shao 1 , Yinzhong Shen 1 , Renfang Zhang 1 , Min Zhang 5 , Meiyan Sun 1 , Tangkai Qi 1 , Zhenyan Wang 1 , Shuibao Xu 1 , Wei Song 1 , Yang Tang 1 , Bihe Zhao 1 , Zichen Song 1 , Jean-Pierre Routy 6 , Hongzhou Lu 3, 7 , Jun Chen 1
Affiliation  

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.



中文翻译:


抗 PD-L1 抗体 ASC22 与组蛋白脱乙酰酶抑制剂西达本胺联合作为无 ART 病毒学控制的“休克和杀伤”策略:一项 II 期单臂研究



ASC22(一种可能增强 HIV 特异性免疫的抗 PD-L1 抗体)和西达本胺(一种 HIV 潜伏逆转剂)的组合可能作为一种无需抗逆转录病毒治疗的 HIV 病毒学控制策略。已实现病毒学抑制的艾滋病毒感染者除接受抗逆转录病毒治疗外,还接受 ASC22 和西达本胺治疗。参与者接受了 24 周的监测,以测量病毒动力学的变化和 HIV 特异性 CD8 + T 细胞的功能 (NCT05129189)。 15 名参与者完成了这项研究。第 8 周时,CA HIV RNA 水平较基线显着增加,停用 ASC22 和西达本胺后该值恢复至基线。 HIV 总 DNA 在第 4 周仅短暂增加( P = 0.014)。相比之下,整合的 HIV DNA 与基线没有显着差异。从基线到第 24 周,观察到效应记忆 CD4 +和 CD8 + T 细胞 ( TEM ) 的比例有所增加(分别为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。然而,在第 8 周,T 细胞功能改善组中 HIV Gag 特异性 T EM细胞的比例与整合 DNA 的改变之间存在负相关(分别为P = 0.042 和P = 0.034)。共收集了 9 起不良事件,全部为 1 级并自行解决。 ASC22 和西达本胺的联合治疗被证明具有良好的耐受性,并且能够有效激活潜在的 HIV 病毒库。 在分析治疗中断的情况下有必要进行进一步的调查。

更新日期:2024-09-09
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