Increasing the in vivo Stability of L-asparaginase through Interactions with HSA

Type of Award: accelerator
Award Number: A-002
Award Period: October 2018 - September 2019
Amount Awarded: $ 100,000.00
PI(s): Arnon Lavie, UIC;

Abstract: L-asparaginase (ASNase) is a cancer drug with a unique mode of action, and copious preclinical data predicts the efficacy of this drug against diverse cancers. However, due to unacceptable side effects, its use is largely limited to acute lymphoblastic leukemia (ALL). The goal of the proposed work is to develop a safer ASNase variant, providing a clinical advantage for use in ALL and other cancers such as pancreatic cancer. To achieve the increased safety profile, we are developing a mammalian ASNase that is predicted to be less immunogenic compared to today's bacterial enzymes. Our humanized variant of the guinea pig ASNase (GpAhum) is devoid of L-glutaminase (GLNase) co-activity. This is crucial, as this co-activity is implicated in many of the drug's toxic side effects. Here we will append a short peptide sequence that, by binding to human serum albumin, will endow the biologic with increased stability and blood circulation time.