Ali F Runa, Larché Mark
Faculty of Medicine, Imperial College, Department of Allergy and Clinical Immunology, Respiratory Immunology Group,Rm 360, Sir Alexander Fleming Building,Faculty of Medicine, Imperial College, London SW7 2AZ, UK.
Expert Rev Vaccines. 2005 Dec;4(6):881-9. doi: 10.1586/14760584.4.6.881.
The T-cell component of the antigen-specific immune response is the target of various novel interventions to modify chronic immunologic disorders, such as allergic diseases. Recent clinical trials have evaluated the safety and efficacy of therapeutic vaccines consisting of short, synthetic, allergen-derived peptides, corresponding to T-cell epitopes from the eliciting antigen. The main advantage of such an approach is the reduction in systemic, immunoglobulin E-mediated adverse events compared with existing whole allergen immunotherapy, often referred to as 'allergy shots'. T-cell peptide epitopes, although capable of inducing immunologic tolerance, are short linear structures that have reduced ability to cross-link mast cell- and basophil-bound immunoglobulin E. The precise mechanism of tolerance induction remains incompletely defined. However, recent data indicate that peptide therapy induces/expands a population of antigen-specific regulatory T-cells. A novel form of treatment combining efficacy with a substantially decreased occurrence of adverse events is likely to have a major impact on the management and prevalence of allergic diseases. Furthermore, the principles of epitope-specific therapy hold promise for the development of therapeutic vaccines for the treatment of autoimmune diseases.
抗原特异性免疫反应中的T细胞成分是各种旨在改善慢性免疫紊乱(如过敏性疾病)的新型干预措施的靶点。最近的临床试验评估了由短的、合成的、源自过敏原的肽组成的治疗性疫苗的安全性和有效性,这些肽对应于引发抗原的T细胞表位。与现有的全过敏原免疫疗法(通常称为“过敏针”)相比,这种方法的主要优点是全身性免疫球蛋白E介导的不良事件减少。T细胞肽表位虽然能够诱导免疫耐受,但它们是短的线性结构,交联肥大细胞和嗜碱性粒细胞结合的免疫球蛋白E的能力降低。耐受诱导的确切机制仍不完全清楚。然而,最近的数据表明,肽疗法可诱导/扩大一群抗原特异性调节性T细胞。一种将疗效与不良事件发生率大幅降低相结合的新型治疗方法可能会对过敏性疾病的管理和流行产生重大影响。此外,表位特异性治疗的原则有望用于开发治疗自身免疫性疾病的治疗性疫苗。