抗体
天冬酰胺酶
PEG比率
连接器
医学
同型
聚乙二醇
单克隆抗体
化学
免疫学
药理学
淋巴细胞白血病
白血病
生物化学
经济
操作系统
计算机科学
财务
作者
Robin Q.H. Kloos,Inge M. van der Sluis,Enrico Mastrobattista,Wim E. Hennink,Rob Pieters,Jan‐Jaap Verhoef
摘要
Summary Polyethylene glycol (PEG) conjugated asparaginase (PEGasparaginase) is essential for treatment of paediatric acute lymphoblastic leukaemia. We developed an assay identifying antibodies against the PEG‐moiety, the linker and the drug itself in patients experiencing hypersensitivity reactions to PEGasparaginase. Eighteen patients treated according to the DCOG ALL‐11 protocol, with a neutralizing hypersensitivity reaction to PEGasparaginase to the first PEGasparaginase doses in induction (12 patients) or during intensification after interruption of several months (6 patients) were included. ELISA was used to measure antibodies, coating with the succinimidyl succinate linker conjugated to BSA, PEGfilgrastim and Escherichia coli asparaginase, and using hydrolysed PEGasparaginase and mPEG 5,000 for competition. Anti‐PEG antibodies were detected in all patients (IgG 100%; IgM 67%) of whom 39% had anti‐PEG antibodies exclusively. Pre‐existing anti‐PEG antibodies were also detected in patients who not previously received a PEGylated therapeutic (58% IgG; 21% IgM). Antibodies against the SS‐linker were predominantly detected during induction (50% IgG; 42% IgM). Anti‐asparaginase antibodies were detected in only 11% during induction but 94% during intensification. In conclusion, anti‐PEG and anti‐SS‐linker antibodies predominantly play a role in the immunogenic response to PEGasparaginase during induction. Thus, switching to native E. coli asparaginase would be an option for adequate asparaginase treatment.
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