Evolving Strategies to Eliminate the CD4 T Cells HIV Viral Reservoir via CAR T Cell Immunotherapy.
Evolving Strategies to Eliminate the CD4 T Cells HIV Viral Reservoir via CAR T Cell Immunotherapy.
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DOI：
10.3389/fimmu.2022.873701
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发表时间：
2022
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
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作者：
尽管抗逆转录病毒疗法（ART）的出现显著降低了与HIV感染相关的发病率和死亡率，但潜伏感染细胞中稳定存在的HIV库需要患者终身坚持治疗，一旦停止ART，病毒就会迅速重新激活并引发具有复制能力的HIV感染。因此，这些为数不多的含有具有复制能力HIV的细胞，即所谓的潜伏HIV储存库，成为了免疫清除和治愈HIV的主要障碍。虽然已经探索了多种策略，包括使HIV在潜伏感染细胞中沉默或重新激活以便通过免疫反应将其清除，但令人振奋的基于细胞的免疫疗法，即利用表达合成嵌合受体的基因工程T细胞（CAR - T细胞）极具吸引力且前景广阔。与内源性细胞毒性T细胞不同，CAR - T细胞能够独立于主要组织相容性复合体（MHC）发挥作用，以靶向HIV感染细胞，疗效显著，并且已证明其在安全性方面可接受，且能在外周血中长期存续。在这篇综述中，我们全面阐述了目前针对HIV潜伏储存库所做的努力，重点聚焦于CAR - T细胞疗法。我们突出了该领域当前面临的挑战和取得的进展，同时探讨了新型CAR设计在寻求治愈HIV过程中的重要性。
Although the advent of ART has significantly reduced the morbidity and mortality associated with HIV infection, the stable pool of HIV in latently infected cells requires lifelong treatment adherence, with the cessation of ART resulting in rapid reactivation of the virus and productive HIV infection. Therefore, these few cells containing replication-competent HIV, known as the latent HIV reservoir, act as the main barrier to immune clearance and HIV cure. While several strategies involving HIV silencing or its reactivation in latently infected cells for elimination by immune responses have been explored, exciting cell based immune therapies involving genetically engineered T cells expressing synthetic chimeric receptors (CAR T cells) are highly appealing and promising. CAR T cells, in contrast to endogenous cytotoxic T cells, can function independently of MHC to target HIV-infected cells, are efficacious and have demonstrated acceptable safety profiles and long-term persistence in peripheral blood. In this review, we present a comprehensive picture of the current efforts to target the HIV latent reservoir, with a focus on CAR T cell therapies. We highlight the current challenges and advances in this field, while discussing the importance of novel CAR designs in the efforts to find a HIV cure.
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