The immunogenicity of biopharmaceuticals
The immunogenicity of biopharmaceuticals
复制标题
生物药物的免疫原性
作者：
H. Schellekens
蛋白质的医学应用有着悠久的历史。它始于世纪以前，当时引入动物源性免疫血清用于预防或治疗感染，几十年后使用猪和牛源性胰岛素。这些产品在患者中具有免疫原性，有时甚至导致严重的过敏反应。这些副作用很容易解释为蛋白质的外来性质导致了经典的免疫反应。
生长激素和第八因子等人源蛋白质的引入也与抗体的诱导有关。然而，这些产品主要用于先天性缺陷的儿童，因此缺乏免疫耐受性。
随着重组DNA技术的发展，大规模生产人类同源物如干扰素（IFN），生长因子和激素变得可行，从而为大量患者提供应用。令人惊讶的是，这些产品也诱导抗体，这不能用缺乏免疫耐受来解释。一些潜在的机制参与生产的抗体重组.
The medical use of proteins has a long history. It started more than one century ago when immune sera of animal origin were introduced for the prevention or treatment of infections, followed by the use of insulin of porcine and bovine origin some decades later. These products were immunogenic in patients, sometimes even leading to serious anaphylactic reactions. These side effects were easily explained by the foreign nature of the proteins leading to a classic immune reaction.
The introduction of human-derived proteins, such as growth hormone and factor VIII, also was associated with the induction of antibodies. However, these products were mostly given to children with an innate deficiency and therefore a lack of immune tolerance.
With the development of recombinant DNA technology, the large-scale production of human homologues like the interferons (IFNs), growth factors, and hormones became feasible, resulting in the application for a large number of patients. It was a surprise that these products also induced antibodies, which cannot be explained by the lack of immune tolerance. Some of the potential mechanisms involved in the production of antibodies to recombinant …