Acute lymphoblastic leukaemia patients treated with PEGasparaginase develop antibodies to PEG and the succinate linker
| Autor: | Kloos, Robin, van der Sluis, Inge M, Mastrobattista, Enrico, Hennink, Wim, Pieters, Rob, Verhoef, Jan-Jaap, Afd Pharmaceutics, Pharmaceutics |
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| Přispěvatelé: | Afd Pharmaceutics, Pharmaceutics, Pediatrics |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Drug
Male Asparaginase media_common.quotation_subject Succinic Acid Polyethylene glycol acute lymphoblastic leukemia Pharmacology Polyethylene Glycols 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine PEG ratio Medicine Humans antibodies media_common biology business.industry Hematology Precursor Cell Lymphoblastic Leukemia-Lymphoma Hypersensitivity reaction chemistry 030220 oncology & carcinogenesis biology.protein Female PEGasparaginase Antibody business Linker Pegfilgrastim 030215 immunology medicine.drug |
| Zdroj: | British Journal of Haematology, 189(3), 442. Wiley-Blackwell British Journal of Haematology, 189(3), 442-451. Wiley-Blackwell Publishing Ltd |
| ISSN: | 1365-2141 0007-1048 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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