L-Asparaginase (ASNase) is a non-human enzyme that hydrolyses the amino acid Asparagine (Asn) into aspartic acid and ammonia. It is used in the clinic as a cornerstone drug for the treatment of acute lymphoblastic leukemia (ALL). Evidence is accumulating that asparaginase may also have clinical potential for the treatment of certain aggressive solid cancer subtypes.

However, especially in adult patients, ASNase administration is often associated with severe immunological side-effects and non-immune related toxicities like pancreatitis, liver toxicities, coagulopathy and neurotoxicity. These unwanted side-effects cause treatment delays or discontinuation, eventually resulting in significant lower cure rates for adult ALL. In addition, because of the tolerability/toxicity issues in adults, the clinical potential of ASNase for the treatment of certain solid cancer subtypes has not been fully pursued.

One could speculate that the development of less toxic and less immunogenic L-asparaginase (ASNase) variants could drastically improve the outcome of adult ALL patients and expand its use to many other aggressive subtypes of human cancer with an overall bad outcome.