Cancer letters · 2024
A human-like glutaminase-free asparaginase is highly efficacious in ASNSlow leukemia and solid cancer mouse xenograft models.
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Van Trimpont Maaike, Schalk Amanda M, Hofkens Kenneth, Peeters Evelien, T'Sas Sara, Vandemeulebroecke Katrien, Su Ying, De Loera Ashley, Garcia Alyssa, Chen Hui, Lammens Tim, Van Vlierberghe Pieter, Goossens Steven, Lavie Arnon
Аннотация
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.