Rational engineering and insight for a L-glutaminase activity reduced type II L-asparaginase from Bacillus licheniformis and its antileukemic activity in vitro

Production Process Optimization of Recombinant Erwinia carotovora l-Asparaginase II in Escherichia coli Fed-Batch Cultures and Analysis of Antileukemic Potential

“…Despite being identified in various sources, only asparaginases from Escherichia coli and Erwinia chrysanthemi have been approved for use in chemotherapy. ,, E. coli -derived preparations have been approved by the FDA for use in ALL and are indicated in most first-line therapies; and Erwinia derivatives are approved for patients who develop hypersensitivity reactions to E. coli -derived enzymes. , These preparations can become immunogenic, and their clinical efficacy is limited by the development of antiasparaginase antibodies which are associated with a decrease in enzyme activity and accompanied by the presence of hypersensitivity reactions. , l -Asparaginase is associated with adverse reactions, with reaction rates of 30 to 70% when the E. coli -derived enzyme is administered. , Once hypersensitivity reactions occur, it is necessary to change the l -asparaginase preparation to one which is not cross-reactive. The therapy can be continued with alternative l -asparaginases until a new limiting immune reaction occurs.…”

“…atroseptica is an alternative to other preparations, as it has a significantly lower l -glutaminase activity than the enzymes from E. coli and E. chrysanthemi. , This is a significant factor, since l -glutaminase activity in therapeutic preparations has been associated with undesirable side effects. ,,,, …”