A human-like glutaminase-free asparaginase is highly efficacious in ASNSlow leukemia and solid cancer mouse xenograft models

L-asparaginase (L-ASNase) is crucial in treating pediatric acute lymphoblastic leukemia (ALL), but its use is hampered by side effects from the immunogenicity and L-glutaminase (L-GLNase) co-activity of FDA-approved bacterial L-ASNases, often leading to treatment discontinuation and poor outcomes. The toxicity of these L-ASNases makes them especially challenging to use in adult cancer patients. To overcome these issues, we developed EBD-200, a humanized guinea pig L-ASNase with low Km and no L-GLNase activity, eliminating glutamine-related toxicity. EBD-200 showed comparable anti-cancer effects to PEGylated L-ASNase in ASNS<sup>low</sup> ALL, melanoma and liver cancer models, with improved tolerability. Its potent anti-cancer efficacy and enhanced safety profile suggest that EBD-200 could benefit ALL patients and broaden treatment options for ASNS<sup>low</sup> solid cancers.

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Publication Details

Journal
Cancer Letters
Published
2024-12-19
DOI
https://doi.org/10.1016/j.canlet.2024.217404
Citations
6
Primary Topic
Acute Lymphoblastic Leukemia research
Type
article
Field-Weighted Citation Impact
3.26

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article

A human-like glutaminase-free asparaginase is highly efficacious in ASNSlow leukemia and solid cancer mouse xenograft models

Maaike Van Trimpont, Steven Goossens, Tim Lammens, Amanda M. Schalk et al.
6 citations
Cancer Letters
Acute Lymphoblastic Leukemia research
3.26
article

A human-like glutaminase-free asparaginase is highly efficacious in ASNSlow leukemia and solid cancer mouse xenograft models

Maaike Van Trimpont, Steven Goossens, Tim Lammens, Amanda M. Schalk, Evelien Peeters, Pieter Van Vlierberghe, Katrien Vandemeulebroecke, Arnon Lavie, A. García, Sara T’Sas, Ying Su, Hui Chen, Kenneth Hofkens, Ashley De Loera
article en
6 citations

Abstract

L-asparaginase (L-ASNase) is crucial in treating pediatric acute lymphoblastic leukemia (ALL), but its use is hampered by side effects from the immunogenicity and L-glutaminase (L-GLNase) co-activity of FDA-approved bacterial L-ASNases, often leading to treatment discontinuation and poor outcomes. The toxicity of these L-ASNases makes them especially challenging to use in adult cancer patients. To overcome these issues, we developed EBD-200, a humanized guinea pig L-ASNase with low Km and no L-GLNase activity, eliminating glutamine-related toxicity. EBD-200 showed comparable anti-cancer effects to PEGylated L-ASNase in ASNS<sup>low</sup> ALL, melanoma and liver cancer models, with improved tolerability. Its potent anti-cancer efficacy and enhanced safety profile suggest that EBD-200 could benefit ALL patients and broaden treatment options for ASNS<sup>low</sup> solid cancers.

Cancer LettersVol. 611
Ghent University Hospital (BE), Ghent University (BE), University of Illinois Chicago (US), University of Chicago (US), IONICS Mass Spectrometry (Canada) (CA), Cancer Research Institute Ghent (BE)
U.S. Department of Veterans Affairs, Universiteit Gent, Vlaamse regering, National Institutes of Health, University of Illinois at Urbana-Champaign
Zero hunger
Openalex Percentile: Top 7%
Acute Lymphoblastic Leukemia research
3.26
DOIOpen Access PDFOpenAlex
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