Wu Te-Lang, Ertl Hildegund C J
University of Pennsylvania School of Medicine, The Wistar Institute, 3601 Spruce St, Philadelphia, PA 19104, USA.
Trends Mol Med. 2009 Jan;15(1):32-9. doi: 10.1016/j.molmed.2008.11.005. Epub 2008 Dec 26.
Immune responses to viral vectors pose one of the main obstacles to successful human gene replacement therapy, unless gene transfer vectors are applied to immune-privileged sites. Both innate and adaptive immunity work in concert against sustained gene transfer, but the functions of patients' regulatory T cells (Tregs) and tolerogenic dendritic cells (DCs) could potentially be harnessed to reduce these immune responses. Over the last few years, immunologists have gained an ever-increasing knowledge of immunoregulatory pathways, especially those that prevent or dampen adaptive immune responses. The gene therapy community is now in a position to use this expanding knowledge in basic immunology to overcome the so far nearly unsurpassable obstacles posed by the immune system to the long-term replacement of missing or faulty genes by the use of viral vectors. Here, we discuss the current challenges in overcoming immune barriers to gene therapy. In addition, we point out potential strategies that might allow circumvention of cellular or humoral immune responses against the vector or the transgene product.
除非将基因转移载体应用于免疫赦免部位，否则对病毒载体的免疫反应是人类基因替代疗法成功的主要障碍之一。先天性免疫和适应性免疫协同作用以对抗持续的基因转移，但患者调节性T细胞（Tregs）和耐受性树突状细胞（DCs）的功能有可能被利用来减少这些免疫反应。在过去几年中，免疫学家对免疫调节途径，尤其是那些预防或抑制适应性免疫反应的途径，有了越来越多的了解。基因治疗界现在能够利用基础免疫学中不断扩展的这一知识，来克服迄今为止免疫系统对使用病毒载体长期替代缺失或有缺陷基因所造成的几乎无法逾越的障碍。在此，我们讨论克服基因治疗免疫障碍方面的当前挑战。此外，我们指出了一些潜在策略，这些策略可能允许规避针对载体或转基因产物的细胞免疫或体液免疫反应。
