Apitope International NV, Diepenbeek, Belgium.
Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom.
Front Immunol. 2021 Sep 9;12:742695. doi: 10.3389/fimmu.2021.742695. eCollection 2021.
The immune response to exogenous proteins can overcome the therapeutic benefits of immunotherapies and hamper the treatment of protein replacement therapies. One clear example of this is haemophilia A resulting from deleterious mutations in the FVIII gene. Replacement with serum derived or recombinant FVIII protein can cause anti-drug antibodies in 20-50% of individuals treated. The resulting inhibitor antibodies override the benefit of treatment and, at best, make life unpredictable for those treated. The only way to overcome the inhibitor issue is to reinstate immunological tolerance to the administered protein. Here we compare the various approaches that have been tested and focus on the use of antigen-processing independent T cell epitopes (apitopes) for tolerance induction. Apitopes are readily designed from any protein whether this is derived from a clotting factor, enzyme replacement therapy, gene therapy or therapeutic antibody.
针对外源性蛋白质的免疫反应可能会削弱免疫疗法的治疗效果，并阻碍蛋白质替代疗法的治疗。血友病 A 就是一个明显的例子，其是由 FVIII 基因的有害突变引起的。用血清衍生或重组 FVIII 蛋白替代治疗会导致 20-50%的治疗个体产生抗药物抗体。由此产生的抑制剂抗体削弱了治疗效果，使治疗者的生活变得不可预测。克服抑制剂问题的唯一方法是重新建立对给予的蛋白质的免疫耐受。在这里，我们比较了已经测试过的各种方法，并重点介绍了使用抗原处理非依赖性 T 细胞表位（apitopes）进行耐受诱导。apitopes 可以很容易地从任何蛋白质中设计出来，无论这种蛋白质是来自凝血因子、酶替代疗法、基因疗法还是治疗性抗体。
