Immunogenicity of Aggregates of Recombinant Human Growth Hormone in Mouse Models
Immunogenicity of Aggregates of Recombinant Human Growth Hormone in Mouse Models
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DOI：
10.1002/jps.21834
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发表时间：
2009-09-01
影响因子：
3.8
通讯作者：
Randolph, Theodore W.
中科院分区：
文献类型：
--
作者：
Fradkin, Amber Haynes;Carpenter, John F.;Randolph, Theodore W.
重组治疗性蛋白产品的聚集是一个令人担忧的问题，因为它们有可能诱导免疫反应。我们检查了通过冻融或搅拌产生的重组人生长激素商业制剂中蛋白质聚集体的免疫原性，这两种压力是治疗性蛋白质产品的制造、运输和处理过程中经常遇到的两种压力。此外，我们对每种制剂进行了高压处理，以减少样品中存在的聚集体的尺寸和浓度。商业制剂中存在的聚集体以及冻融和搅拌应激诱导的聚集体增强了一种或多种小鼠模型中的免疫原性。使用高压处理来减少重组人生长激素制剂中聚集体的大小和浓度，降低了它们的整体免疫原性，这与“免疫”假说一致。 (c) 2009 Wiley-Liss, Inc. 和美国药剂师协会 J Pharm Sci 98:3247-3264, 2009
Aggregation of recombinant therapeutic protein products is a concern due to their potential to induce immune responses. We examined the immunogenicity of protein aggregates in commercial formulations of recombinant human growth hormone produced by freeze-thawing or agitation, two stresses commonly encountered during manufacturing, shipping and handling of therapeutic protein products. In addition, we subjected each preparation to high-pressure treatment to reduce the size and concentration of aggregates present in the samples. Aggregates existing in a commercial formulation, as well as aggregates induced by freeze-thawing and agitation stresses enhanced immunogenicity in one or more mouse models. The use of high-pressure treatment to reduce size and concentrations of aggregates within recombinant human growth hormone formulations reduced their overall immunogenicity in agreement with the "immunon" hypothesis. (c) 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:3247-3264, 2009