Production of “biobetter” variants of glucarpidase with enhanced enzyme activity

Introduction Methotrexate intoxication following high-dose methotrexate-induced acute kidney injury is a life-threatening complication. Glucarpidase can quickly reduce extracellular methotrexate to safe levels, but the effectiveness and safety of its use in different episodes of nephrotoxicity remain an unknown area. Case Report A 30-year-old male diagnosed with acute lymphoblastic T-cell lymphoma received methotrexate 5 g/m2 intravenous (IV) as part of the first consolidation cycle. On Consolidation 3, he restarted methotrexate at a dose of 3 g/m2 IV showing slow methotrexate elimination, associated myelosuppression, and hepatic toxicity. Glucarpidase was administered (total dose of 2000 International Units (IU)). No adverse events were observed, and his renal function returned to normal. One hundred and six days later, he was diagnosed with leptomeningeal and cerebellar relapse and treatment with methotrexate 3,5 g/m2 IV day 1 and cytosine arabinoside (Ara-C) 2 g/m2 IV twice per day days 1, 3, and 5 was started. At 36 h from methotrexate infusion, serum creatinine increased up to 1.89 mg/dL and methotrexate concentration was 100 µmol/L. Management and Outcome: Ara-C was suspended, and a second administration of glucarpidase (2000 IU) was dispensed. No adverse events were noticed, methotrexate levels decreased and renal function progressively improved, recovering completely three weeks later. Discussion The effectiveness and safety of the use of glucarpidase in different episodes of nephrotoxicity remain an unknown area, and the rate and consequences of antiglucarpidase antibody formation remain poorly understood. This case report is, to our knowledge, the first case of a second administration of glucarpidase in a different cycle of high-dose methotrexate in an adult patient.

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“…9 Trying to reduce immunogenicity and increase activity, novel “biobetter” variants of glucarpidase are under investigation. 13,14…”

Section: Discussionmentioning

confidence: 99%

A second administration of glucarpidase in a different cycle of high-dose methotrexate: Is it safe and effective in adults?

Domingo‐González

Osorio

Landete

et al. 2020

J Oncol Pharm Pract

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“…There was a spelling error in the second author's name. Although the corresponding author referenced the original source [1] in the later article [2], he acknowledges that it should have also been indicated in the figure legend of the article [2]. The PLOS ONE Editors have assessed this issue and have no concerns about the reuse of the image from [1].…”

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confidence: 99%

Correction: Isolation and molecular characterization of novel glucarpidases: Enzymes to improve the antibody directed enzyme pro-drug therapy for cancer treatment

Rashidi,

Al-Qahtani,

Bashraheel

et al. 2023

PLoS ONE

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Characterization of a Stable Form of Carboxypeptidase G2 (Glucarpidase), a Potential Biobetter Variant, From Acinetobacter sp. 263903-1

Sadeghian

Hemmati

2021

Mol Biotechnol

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Production of “biobetter” variants of glucarpidase with enhanced enzyme activity

Cited by 9 publications

References 32 publications

A second administration of glucarpidase in a different cycle of high-dose methotrexate: Is it safe and effective in adults?

A second administration of glucarpidase in a different cycle of high-dose methotrexate: Is it safe and effective in adults?

Correction: Isolation and molecular characterization of novel glucarpidases: Enzymes to improve the antibody directed enzyme pro-drug therapy for cancer treatment

Characterization of a Stable Form of Carboxypeptidase G2 (Glucarpidase), a Potential Biobetter Variant, From Acinetobacter sp. 263903-1

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