Tolera Therapeutics Inc, 350 E Michigan Ave Ste 205, Kalamazoo, MI 49007, USA.
Immunotherapy. 2011 Jul;3(7):853-70. doi: 10.2217/imt.11.61.
In recent years, substantial advances in T-cell immunosuppressive strategies and their translation to routine clinical practice have revolutionized management and outcomes in autoimmune disease and solid organ transplantation. More than 80 diseases have been considered to have an autoimmune etiology, such that autoimmune-associated morbidity and mortality rank as third highest in developed countries, after cardiovascular diseases and cancer. Solid organ transplantation has become the therapy of choice for many end-stage organ diseases. Short-term outcomes such as patient and allograft survival at 1 year, acute rejection rates, as well as time course of disease progression and symptom control have steadily improved. However, despite the use of newer immunosuppressive drug combinations, improvements in long-term allograft survival and complete resolution of autoimmunity remain elusive. In addition, the chronic use of nonspecifically targeted immunosuppressive drugs is associated with significant adverse effects and increased morbidity and mortality. In this article, we discuss the current clinical tools for immune suppression and attempts to induce long-term T-cell tolerance induction as well as much-needed future approaches to produce more short-acting, antigen-specific agents, which may optimize outcomes in the clinic.
近年来,T 细胞免疫抑制策略取得了重大进展,并已将其转化为常规临床实践,从而彻底改变了自身免疫性疾病和实体器官移植的治疗方法和结果。超过 80 种疾病被认为具有自身免疫病因,因此,在发达国家,自身免疫相关的发病率和死亡率仅次于心血管疾病和癌症,位居第三。实体器官移植已成为许多终末期器官疾病的首选治疗方法。短期结果(如患者和移植物 1 年存活率、急性排斥反应率以及疾病进展和症状控制的时间过程)稳步改善。然而,尽管使用了新的免疫抑制药物组合,长期移植物存活率的提高和自身免疫的完全缓解仍然难以实现。此外,长期使用非特异性靶向免疫抑制药物会导致严重的不良反应,并增加发病率和死亡率。在本文中,我们讨论了目前用于免疫抑制的临床工具,以及诱导长期 T 细胞耐受的尝试,以及急需未来的方法来产生更具短期疗效、抗原特异性的药物,这可能会优化临床治疗效果。