Division of Hematology/Oncology, Department of Medicine, The UCLA AIDS Institute, Los Angeles, California, USA.
Curr Opin HIV AIDS. 2011 Jan;6(1):68-73. doi: 10.1097/COH.0b013e3283412370.
Stem cell-based strategies for treating HIV-infected individuals represent a novel approach toward reconstituting the ravaged immune system with the ultimate aim of clearing the virus from the body. Genetic modification of human hematopoietic stem cells to produce cells that are either resistant to infection, cells that produce lower amounts of infectious virus, or cells that specifically target the immune response against the virus are currently the dominant strategies under development. This review focuses on the understanding of stem cell-based approaches that are under investigation and the rationale behind such approaches.
Significant progress has recently been made utilizing stem cell-based approaches to treat HIV infection. Ideally, a successful strategy would result in immune clearance of the virus from the body as well long-term restoration of overall immune responses to successfully combat everyday environmental antigens. Two recent clinical trails illustrate how new advances in stem cell-based approaches may propel this field forward to clinical reality: one that demonstrates that large-scale gene therapy trials can be performed in a conventional, reproducible manner; and one that demonstrates the utilization of a multipronged approach using lentiviral-based gene therapy vectors. These clinical trails serve as the foundation for the development of other technologies, discussed here, that are currently in preclinical development.
Recent advances using stem cell-based approaches to treat HIV infection have provided the impetus for a renewed and expanded interest in the development of new cell-based strategies to treat HIV infection as well as a variety of other diseases.
基于干细胞的策略治疗 HIV 感染个体代表了一种用重建被破坏的免疫系统的新方法,最终目的是从体内清除病毒。目前,正在开发的主要策略是对人类造血干细胞进行基因修饰,以产生对感染有抗性、产生较少传染性病毒的细胞,或专门针对病毒免疫反应的细胞。这篇综述重点介绍了正在研究中的基于干细胞的方法的理解和这些方法背后的原理。
最近在利用基于干细胞的方法治疗 HIV 感染方面取得了重大进展。理想情况下,一个成功的策略将导致病毒从体内被免疫清除,以及整体免疫反应的长期恢复,以成功对抗日常环境抗原。最近的两项临床试验说明了基于干细胞的方法的新进展如何推动这一领域走向临床现实:一项表明可以以常规、可重复的方式进行大规模基因治疗试验;另一项表明利用基于慢病毒的基因治疗载体的多管齐下的方法。这些临床试验为其他技术的发展奠定了基础,这里讨论的技术目前处于临床前开发阶段。
最近利用基于干细胞的方法治疗 HIV 感染的进展为开发新的基于细胞的策略治疗 HIV 感染以及各种其他疾病提供了新的动力和扩展的兴趣。