Wolinella Asparaginase as an Immunologically Distinct, Efficacious, and Potentially Less Toxic Asparaginase for Use in Lymphoid Malignancies.

L-asparaginase targets the protein translational mechanism and is an essential component in the treatment of acute lymphoblastic leukemia (ALL) and lymphoid malignancies. The current available preparations, E. coli and Erwinia have significant toxicities, often limiting their clinical use. In order to provide patients with a novel form of asparaginase, a recombinant form of Wolinella (rWS) asparaginase was developed. C3H mice were transplanted with 2 × 10⁶ 6C3HED lymphoma cells. Mice treated with native or rWS asparaginase demonstrated a significant decrease in tumor volume, and they remained tumor free for greater than 30 days after treatment. Human ALL cell lines were tested for sensitivity to rWS asparaginase and the molecular basis for rWS asparaginase sensitivity was examined in these cells. We hypothesized that rWS asparaginase would be immunologically distinct to that of E. coli. The sera of 6 patients previously identified to have high titer inhibitors to E. coli asparaginase were tested for antibodies to rWS asparaginase. The antibodies to E. coli did not bind to the rWS asparaginase, therefore demonstrating that there is no cross-reactivity to rWS asparaginase. Thus, antibodies or hypersensitivity reactions to previous forms of asparaginase will not prohibit therapy with rWS asparaginase. Therefore rWS asparaginase represents the first recombinant form of asparaginase and shows promise as a novel form of asparaginase which is immunologically distinct from E. coli and Erwinia asparaginase. In addition, it appears to be equally efficacious, and in previously published data, may have less toxicity. Asparaginase is an important component of treatment regimens for lymphoid malignancies, and therefore future studies will include a Phase I/II trial utilizing rWS asparaginase in relapsed lymphoid malignancies.