Immunogenicity of protein therapeutics: The key causes, consequences and challenges.
Immunogenicity of protein therapeutics: The key causes, consequences and challenges.
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DOI：
10.4161/self.1.4.13904
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发表时间：
2010-10-01
期刊：
影响因子：
--
通讯作者：
Bryson, Christine J
中科院分区：
文献类型：
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作者：
Baker, Matthew P;Reynolds, Helen M;Bryson, Christine J
迄今为止，蛋白质治疗剂的免疫原性已被证明难以在患者中预测，许多生物制剂诱导针对治疗剂的不期望的免疫应答，导致降低的功效、过敏反应和偶尔危及生命的自身免疫。施用免疫原性蛋白质治疗剂的最常见效应是产生高亲和力抗治疗性抗体应答。此外，从临床研究中清楚的是，来源于内源性人蛋白质的蛋白质治疗剂能够刺激患者中不期望的免疫应答，因此，免疫原性的预测和降低已经成为深入研究的焦点。本综述将概述蛋白质治疗中免疫原性的主要原因，并描述临床前模型的发展，该模型可用于帮助预测新型蛋白质治疗剂在人体给药前的免疫原性潜力。
The immunogenicity of protein therapeutics has so far proven to be difficult to predict in patients, with many biologics inducing undesirable immune responses directed towards the therapeutic resulting in reduced efficacy, anaphylaxis and occasionally life threatening autoimmunity. The most common effect of administrating an immunogenic protein therapeutic is the development of a high affinity anti-therapeutic antibody response. Furthermore, it is clear from clinical studies that protein therapeutics derived from endogenous human proteins are capable of stimulating undesirable immune responses in patients, and as a consequence, the prediction and reduction of immunogenicity has been the focus of intense research. This review will outline the principle causes of the immunogenicity in protein therapeutics, and describe the development of pre-clinical models that can be used to aid in the prediction of the immunogenic potential of novel protein therapeutics prior to administration in man.