Mukovozov Ilya, Sabljic Thomas, Hortelano Gonzalo, Ofosu Frederick A
Department of Pathology and Molecular Medicine, McMaster University, 1200 Main Street West, HSC 3N26, Hamilton, ON, Canada L8N 3Z5.
Thromb Haemost. 2008 May;99(5):874-82. doi: 10.1160/TH07-11-0654.
Use of recombinant human proteins has revolutionized medicine by providing over 200 highly purified hormones and proteins that effectively treat many inherited and acquired peptide hormone and protein deficiencies. With the exception of therapeutic monoclonal antibodies, these biological medicines are synthesized by cultured cells using DNA sequences that would yield proteins with identical amino acid sequences as endogenous human proteins. Therefore, there was the broad expectation that recombinant human biological medicines would be non-immunogenic in patients capable of synthesizing even sub-optimal levels of these therapeutic proteins to which they are innately tolerant. However, the widespread clinical use of recombinant human proteins has demonstrated that nearly all of them are immunogenic. This observation suggests that factors additional to differences in amino acid sequences of endogenous and biotherapeutic proteins contribute to the immunogenicity of therapeutic proteins. The main aim of this review is to summarize some of the factors that are known to contribute to the immunogenicity of recombinant therapeutic proteins.
重组人蛋白的使用彻底改变了医学，它提供了200多种高度纯化的激素和蛋白质，有效治疗了许多遗传性和后天性肽类激素及蛋白质缺乏症。除治疗性单克隆抗体外，这些生物药物是通过培养细胞利用DNA序列合成的，所产生的蛋白质与内源性人类蛋白质具有相同的氨基酸序列。因此，人们普遍期望重组人生物药物在能够合成即使是次优水平的这些自身先天耐受的治疗性蛋白质的患者中不会具有免疫原性。然而，重组人蛋白在临床上的广泛应用表明，几乎所有这些蛋白都具有免疫原性。这一观察结果表明，除了内源性和生物治疗性蛋白质氨基酸序列的差异外，还有其他因素导致治疗性蛋白质具有免疫原性。本综述的主要目的是总结一些已知的导致重组治疗性蛋白质免疫原性的因素。
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