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

Maaike Van Trimpont (UGent) , Amanda M. Schalk, Kenneth Hofkens (UGent) , Evelien Peeters (UGent) , Sara T'Sas (UGent) , Katrien Vandemeulebroecke (UGent) , Ying Su, Ashley De Loera, Alyssa Garcia, Hui Chen, et al.
(2025) CANCER LETTERS. 611.
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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 ASNSlow 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 ASNSlow solid cancers.
Keywords
Asparagine synthetase, Acute lymphoblastic leukemia, ASNS low solid tumors, Liver cancer, Melanoma, ACUTE LYMPHOBLASTIC-LEUKEMIA, POLYETHYLENE-GLYCOL, VIBRIO-SUCCINOGENES, CLINICAL-EVALUATION, ESCHERICHIA-COLI, PHASE-I, SYNTHETASE, IDENTIFICATION, ENZYME, HYPERSENSITIVITY

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Citation

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MLA
Van Trimpont, Maaike, et al. “A Human-like Glutaminase-Free Asparaginase Is Highly Efficacious in ASNS-Low Leukemia and Solid Cancer Mouse Xenograft Models.” CANCER LETTERS, vol. 611, 2025, doi:10.1016/j.canlet.2024.217404.
APA
Van Trimpont, M., Schalk, A. M., Hofkens, K., Peeters, E., T’Sas, S., Vandemeulebroecke, K., … Lavie, A. (2025). A human-like glutaminase-free asparaginase is highly efficacious in ASNS-low leukemia and solid cancer mouse xenograft models. CANCER LETTERS, 611. https://doi.org/10.1016/j.canlet.2024.217404
Chicago author-date
Van Trimpont, Maaike, Amanda M. Schalk, Kenneth Hofkens, Evelien Peeters, Sara T’Sas, Katrien Vandemeulebroecke, Ying Su, et al. 2025. “A Human-like Glutaminase-Free Asparaginase Is Highly Efficacious in ASNS-Low Leukemia and Solid Cancer Mouse Xenograft Models.” CANCER LETTERS 611. https://doi.org/10.1016/j.canlet.2024.217404.
Chicago author-date (all authors)
Van Trimpont, Maaike, Amanda M. Schalk, Kenneth Hofkens, Evelien Peeters, Sara T’Sas, Katrien Vandemeulebroecke, Ying Su, Ashley De Loera, Alyssa Garcia, Hui Chen, Tim Lammens, Pieter Van Vlierberghe, Steven Goossens, and Arnon Lavie. 2025. “A Human-like Glutaminase-Free Asparaginase Is Highly Efficacious in ASNS-Low Leukemia and Solid Cancer Mouse Xenograft Models.” CANCER LETTERS 611. doi:10.1016/j.canlet.2024.217404.
Vancouver
1.
Van Trimpont M, Schalk AM, Hofkens K, Peeters E, T’Sas S, Vandemeulebroecke K, et al. A human-like glutaminase-free asparaginase is highly efficacious in ASNS-low leukemia and solid cancer mouse xenograft models. CANCER LETTERS. 2025;611.
IEEE
[1]
M. Van Trimpont et al., “A human-like glutaminase-free asparaginase is highly efficacious in ASNS-low leukemia and solid cancer mouse xenograft models,” CANCER LETTERS, vol. 611, 2025.
@article{01JH5QZVHWFHYVXC76WP1CKQPA,
  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 ASNSlow 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 ASNSlow solid cancers.}},
  articleno    = {{217404}},
  author       = {{Van Trimpont, Maaike and Schalk, Amanda M. and Hofkens, Kenneth and Peeters, Evelien and T'Sas, Sara and Vandemeulebroecke, Katrien and Su, Ying and De Loera, Ashley and Garcia, Alyssa and Chen, Hui and Lammens, Tim and Van Vlierberghe, Pieter and Goossens, Steven and Lavie, Arnon}},
  issn         = {{0304-3835}},
  journal      = {{CANCER LETTERS}},
  keywords     = {{Asparagine synthetase,Acute lymphoblastic leukemia,ASNS low solid tumors,Liver cancer,Melanoma,ACUTE LYMPHOBLASTIC-LEUKEMIA,POLYETHYLENE-GLYCOL,VIBRIO-SUCCINOGENES,CLINICAL-EVALUATION,ESCHERICHIA-COLI,PHASE-I,SYNTHETASE,IDENTIFICATION,ENZYME,HYPERSENSITIVITY}},
  language     = {{eng}},
  pages        = {{10}},
  title        = {{A human-like glutaminase-free asparaginase is highly efficacious in ASNS-low leukemia and solid cancer mouse xenograft models}},
  url          = {{http://doi.org/10.1016/j.canlet.2024.217404}},
  volume       = {{611}},
  year         = {{2025}},
}
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