E. coli-Derived L-Asparaginase Retains Enzymatic and Cytotoxic Activity In Vitro for Canine and Feline Lymphoma after Cold Storage

Abstract EN

Background.

L-asparaginase is effective in treating canine and feline lymphoma, however chemotherapy poses a significant financial cost to veterinary clients, limiting therapy for many pets.

Single dose vials result in significant drug wastage, and drug shortages limit consistent availability for pets.

Hypothesis.

E.

coli-derived asparaginase retains enzymatic and antineoplastic activity in canine and feline lymphoma cells after cold storage.

Methods.

E.

coli-derived asparaginase was cold-stored: refrigeration (7–14 days) and freezing (14 days–six months, one to three freeze/thaw cycles).

Enzymatic activity of asparaginase was measured via a modified asparagine assay.

Effects of cold-stored asparaginase on cell proliferation and cytotoxicity were measured in feline (MYA-1, F1B) and canine (17–71, OSW) lymphoma cells.

Results.

Cold-stored E.

coli-derived asparaginase retains antineoplastic activity in all four cell lines tested.

Cold-stored E.

coli-derived L-asparaginase depletes asparagine and retains enzymatic activity.

Duration of refrigeration, duration of freezing, and number of freeze-thaw cycles have minimal effect on asparaginase enzyme activity.

Conclusions and Clinical Importance.

This study establishes a scientific basis for long-term cold storage of reconstituted E.

coli-derived asparaginase that may result in better utilization of limited drug resources and improve financial feasibility of E.

coli-derived asparaginase as a therapeutic option for pets with lymphoma.