Immune response elicited by therapeutic proteins is an important safety and efficacy issue for regulatory agencies, drug manufacturers, clinicians, and patients. Administration of therapeutic proteins can potentially induce the production of anti-drug antibodies or cell-mediated immune responses. At first, it was speculated that the immunogenicity is related to the non-human origin of these proteins. Later on, it was confirmed that the human proteins may also show immunogenicity. In this review article, we will focus on a number of factors, which play crucial roles in the human protein immunogenicity. These factors are related to the patient's status (or intrinsic properties) and molecular characteristics of the therapeutic protein's (or extrinsic properties). Furthermore, we will discuss available in silico, in vitro, and in vivo methods for the prediction of sequences, which may generate an immune response following parenteral administration of these proteins. In summary, nowadays, it is possible for drug manufacturers to evaluate the risk of immunogenicity of therapeutic proteins and implement a management plan to overcome the problems prior to proceeding to human clinical trials.

对于调节机构，药物制造商，临床医生和患者而言，治疗性蛋白质引起的免疫反应是重要的安全性和有效性问题。给予治疗性蛋白质可能会诱导产生抗药物抗体或细胞介导的免疫反应。首先，推测免疫原性与这些蛋白质的非人类来源有关。后来，证实了人蛋白也可能显示免疫原性。在这篇综述文章中，我们将关注许多因素，这些因素在人类蛋白质免疫原性中起着至关重要的作用。这些因素与患者的状态（或内在特性）和治疗性蛋白质的分子特性（或外在特性）有关。此外，我们将讨论可用的计算机，用于预测序列的体外和体内方法，在肠胃外施用这些蛋白质后可能会产生免疫反应。总之，如今，药物制造商可以在进行人体临床试验之前评估治疗性蛋白质的免疫原性风险并实施管理计划以克服这些问题。