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 mPEG5,000 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.

中文翻译：

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用PEG天冬酰胺酶治疗的急性淋巴细胞白血病患者产生针对PEG和琥珀酸酯接头的抗体。

聚乙二醇（PEG）结合的天冬酰胺酶（PEGasparaginase）对于治疗小儿急性淋巴细胞白血病至关重要。我们开发了一种测定方法，该方法可识别对PEG天冬酰胺酶发生超敏反应的患者中针对PEG部分，接头和药物本身的抗体。包括18名根据DCOG ALL-11方案治疗的患者，其中包括对PEG天冬酰胺酶的中和超敏反应至诱导中的第一个PEG天冬酰胺酶剂量（12例）或中断数月后的强化治疗（6例）。ELISA用于测量抗体，涂有与BSA，PEGfilgrastim和大肠杆菌天冬酰胺酶缀合的琥珀酰亚胺琥珀酸酯接头，并使用水解的PEG天冬酰胺酶和mPEG5,000进行竞争。在所有患者（IgG 100％； IgM 67％）中检测到抗PEG抗体，其中39％仅具有抗PEG抗体。在以前未接受过聚乙二醇化治疗的患者（58％IgG； 21％IgM）中也检测到了已有的抗PEG抗体。在诱导过程中主要检测到针对SS接头的抗体（50％IgG； 42％IgM）。抗天冬酰胺酶抗体在诱导过程中仅检测到11％，而在强化过程中​​检测到94％。总之，在诱导过程中，抗PEG和抗SS接头抗体在对PEG天冬酰胺酶的免疫原性应答中起主要作用。因此，改用天然大肠杆菌天冬酰胺酶将是适当处理天冬酰胺酶的一种选择。在以前未接受过聚乙二醇化治疗的患者（58％IgG； 21％IgM）中也检测到了已有的抗PEG抗体。在诱导过程中主要检测到针对SS接头的抗体（50％IgG； 42％IgM）。抗天冬酰胺酶抗体在诱导过程中仅检测到11％，而在强化过程中​​检测到94％。总之，在诱导过程中，抗PEG和抗SS接头抗体在对PEG天冬酰胺酶的免疫原性应答中起主要作用。因此，改用天然大肠杆菌天冬酰胺酶将是适当处理天冬酰胺酶的一种选择。在以前未接受过聚乙二醇化治疗的患者（58％IgG； 21％IgM）中也检测到了已有的抗PEG抗体。在诱导过程中主要检测到针对SS接头的抗体（50％IgG； 42％IgM）。抗天冬酰胺酶抗体在诱导过程中仅检测到11％，而在强化过程中​​检测到94％。总之，在诱导过程中，抗PEG和抗SS接头抗体在对PEG天冬酰胺酶的免疫原性应答中起主要作用。因此，改用天然大肠杆菌天冬酰胺酶将是适当处理天冬酰胺酶的一种选择。抗PEG和抗SS-接头抗体主要在诱导过程中对PEG天冬酰胺酶的免疫原性应答中起作用。因此，改用天然大肠杆菌天冬酰胺酶将是适当处理天冬酰胺酶的一种选择。抗PEG和抗SS-接头抗体主要在诱导过程中对PEG天冬酰胺酶的免疫原性应答中起作用。因此，改用天然大肠杆菌天冬酰胺酶将是适当处理天冬酰胺酶的一种选择。