Seattle Children's Research Institute & Department of Pediatrics, University of Washington, Seattle, WA, USA.
Expert Rev Hematol. 2010 Aug;3(4):469-83. doi: 10.1586/ehm.10.33.
Approximately 25-30% of the hemophilia A patients develop inhibitory antibodies against Factor VIII (FVIII) following protein-replacement therapy. This problem is also thought to occur following gene-replacement therapy. Recently, many approaches have been investigated to modulate FVIII-specific immune responses in either protein-replacement or gene therapy hemophilia A mouse models. Several promising protocols have been demonstrated to successfully prevent or modulate the formation of anti-FVIII antibodies, including methods to manipulate antigen presentation, development of less immunogenic FVIII proteins, or formulations or gene therapy protocols to evade immune responses, as well as immunomodulation strategies to target either T- and/or B-cell responses. Most of these successful protocols involve the induction of activated Treg cells to create a regulatory immune environment during tolerance induction. Innovative strategies to overcome pre-existing anti-FVIII immune responses and induce long-term tolerance in primed subjects still need to be developed.
约 25-30%的血友病 A 患者在接受蛋白替代疗法后会针对凝血因子 VIII（FVIII）产生抑制性抗体。人们认为该问题也会在基因替代疗法后发生。最近，许多方法已被用于在蛋白替代或基因治疗血友病 A 小鼠模型中调节 FVIII 特异性免疫反应。几项有前景的方案已被证实可成功预防或调节抗 FVIII 抗体的形成，包括操纵抗原呈递、开发免疫原性较低的 FVIII 蛋白、或制剂或基因治疗方案以逃避免疫反应，以及免疫调节策略以靶向 T 细胞和/或 B 细胞反应。这些成功方案中的大多数都涉及诱导激活的调节性 T 细胞（Treg 细胞），以在诱导耐受时创建一个调节性免疫环境。仍然需要开发创新策略来克服已存在的抗 FVIII 免疫反应并在致敏对象中诱导长期耐受。
