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Mammalian L-asparaginase (specifically developed as EBD-200 and EBD-300 by Enzyme by Design) is a humanized recombinant L-asparaginase derived from guinea pig (GpAhum). Unlike FDA-approved bacterial L-asparaginases (such as those derived from *Escherichia coli* or *Erwinia chrysanthemi*), which are highly immunogenic and possess L-glutaminase co-activity that leads to severe toxicities like pancreatitis and liver damage, this mammalian enzyme is intrinsically devoid of L-glutaminase activity. By selectively hydrolyzing L-asparagine into L-aspartate and ammonia, it depletes extracellular L-asparagine levels, starving asparagine synthetase (ASNS)-deficient cancer cells. Mammalian L-asparaginase is being developed for the treatment of acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), and various ASNS-low solid tumors, offering a potentially safer and less immunogenic therapeutic profile.
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