China
Africa
Explore chapters and articles related to this topic
Anti-PEG Immunity Against PEGylated Therapeutics
Published in Raj Bawa, János Szebeni, Thomas J. Webster, Gerald F. Audette, Immune Aspects of Biopharmaceuticals and Nanomedicines, 2019
Amr S. Abu Lila, Tatsuhiro Ishida
Besides the reports by Richter and Akerblom [19], as well as by Armstrong et al. [14], the prevalence of pre-existing anti-PEG antibodies has been further reported in both healthy donors and untreated controls during clinical trials. Tillmann and coworkers [40] observed the occurrence of relatively low levels of anti-PEG antibodies in healthy individuals (7–8%), whereas a high frequency of anti-PEG antibodies (up to 44%) was detected in patients with hepatitis C. However, these elevated levels of anti-PEG antibodies exerted no compromising effect on the therapeutic efficacy of PEGylated interferon used for the treatment of this chronic disease. Hershfield et al. [43] also reported the pre-existence of up to 19% of anti-PEG antibodies in the sera of control subjects prior to treatment with pegloticase, a PEGylated form of urate oxidase used in the treatment of refractory gout. As a result, the FDA has recently updated their guidelines to screen for anti-PEG antibodies during clinical trials of PEGylated therapeutics [44].
Characterization of a novel marine microbial uricase from Priestia flexa and evaluation of the effects of CMCS conjugation on its enzymatic properties
Published in Preparative Biochemistry & Biotechnology, 2023
YuLiang Jiao, YuYing Zhu, ShuMin Zeng, ShuFang Wang, Jing Chen, XiangHong Zhou, GuiZhen Ma
Commercialized uricase drugs are all terrestrial microorganism sourced such as Uricozyme and Rasburicase (Elitek), both from Aspergillus flavus.[3] They are efficacious in getting symptoms relating to tumor lysis syndrome settled and promptly decreasing serum uric acid.[4] These unmodified uricase can only be administered by intravenous infusion because they will be degraded if they are given by oral administration. However, intravenous infusion inevitably causes immunologic reaction problems and shortens the half-life. To overcome these shortcomings, pegloticase (Krystexxa), a porcine recombinant uricase conjugated to methoxypolyethylene glycol (mPEG) was developed and granted FDA approval in the United States in 2010 for treatment of refractory gout; unfortunately, the development of anti-PEG and anti-uricase antibodies were still observed in clinical practice.[5] Therefore many researchers have started seeking for novel uricase and different modifications. Various biomacromolecules were tried to modify uricase, such as lipid vesicles, dextrin, polyethylene glycol (PEG), and their derivatives.[6–8] These modifications were successful in improving the stability of uricase in serum; however, due to the high molecular mass of uricase and the adjuvants, and more problematically the proteinaceous nature of uricase, none of the current modification geared toward intravenous administration can perfectly resolve the problem of the immunogenicity in long-term use. Besides, the way of infusion administration is not very acceptable by patients and can cause an increased risk for infusion reactions in the long term treatment.[9]