UIC-2016-095 – EbD-100: An Engineered Asparaginase Variant to Improve the Treatment of Acute Lymphoblastic Leukemia(ALL)

Bacterial asparaginases from E. coli and Erwinia chrysanthemi (ErA-WT) have a unique mode of action (MOA) and are key drugs used for the treatment of pediatric ALL. Unfortunately, these asparaginases are highly toxic, especially to adults, making their use for adult ALL patients very challenging. Consequently, many adult ALL patients are not treated with asparaginase, which partially explains the dismal 40% cure rate of adult ALL. The Problem The available asparaginases have dual activity, hydrolyzing both the amino acids asparagine and glutamine.•Barriers to the use of current therapeutics originate from the glutaminase co-activity that contributes to increased adverse effects including liver toxicity, pancreatitis, impaired coagulation and neurotoxicity. UIC Solution EbD-100 (ErA-TM) is an engineered Erwinia L-asparaginase variant that is devoid of glutaminase co-activity. EbD-100 advantages:•Reduced toxicity compared to current therapeutics.•Allows for extended treatment.•Includes innovative half-life extension technology.•Allows for less frequent and lower dosing.•Highly effective against ALL cells in vivo.•Bioluminescent imaging (BLI) signal decreased to <1% after ~2 doses. Nelson Grihalde grihalde@otm.uic.edu 312-996-4129

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