Oral immunotherapies are being developed for various autoimmune diseases and allergies to suppress immune responses in an antigen-specific manner. Previous studies have shown that anti-drug antibody (inhibitor) formation in protein replacement therapy for the inherited bleeding disorder hemophilia can be prevented by repeated oral delivery of coagulation factor antigens bioencapsulated in transplastomic lettuce cells. Here, we find that this approach substantially reduces antibody development against factor VIII in hemophilia A mice treated with adeno-associated viral gene transfer. We propose that the concept of oral tolerance can be applied to prevent immune responses against therapeutic transgene products expressed in gene therapy.

正在开发针对各种自身免疫性疾病和过敏的口服免疫疗法，以抗原特异性方式抑制免疫反应。先前的研究表明，在遗传性出血性疾病血友病的蛋白质替代疗法中，抗药物抗体（抑制剂）的形成可以通过重复口服生物封装在转质体生菜细胞中的凝血因子抗原来预防。在这里，我们发现这种方法大大减少了接受腺相关病毒基因转移治疗的甲型血友病小鼠中针对因子 VIII 的抗体的产生。我们建议口服耐受的概念可用于防止针对基因治疗中表达的治疗性转基因产物的免疫反应。