Asparaginase is central to the treatment of acute lymphoblastic leukemia. However, due to bacterial origin EcA (asparaginase) administration may cause strong immunoge¬nic and hypersensitive reactions in the patients. Sensitive individuals react to repeated EcA administra¬tion with forma¬tion of anti-drug antibodies (ADAs) that bind to and thereby inactivate the enzyme. Another serious drawback is glutaminase activity leading to neurotoxicity.
We have created several EcA variants by rational protein engineering approach. Various in vitro and in vivo experiments on mice model and patient sample revealed that our asparaginase mutants had more thermal and serum stability, less antigenecity, better efficacy and less glutaminase activity. Pharmacokinetic study showed that this mutants stay in the body for more time and eliminate slowly than generics and native asparaginase. Presently, we are in a process of collaborating with an industry partner for the formulation development of our drug, further to which we aim to conduct phase I (first in human) clinica trials at ACTREC.