Out-licensing

Directed Evolution of a Lysosomal Enzyme by Mammalian Cell Surface Display for Improved Anti-Cancer Prodrug Activation

Introduction/Background

Increasing the specificity of chemotherapy may improve the efficacy of cancer treatment.

Aims/Hypothesis

Toward this aim, we developed an improved b-glucuronidase.

Research

The mutant human b-glucuronidase developed here displays enhanced enzymatic activity at physiological pH. It activates glucuronide prodrugs more effectively than native glucuronidase. Selective targeting of this enzyme to tumours enhances treatment of cancer by glucuronide prodrugs. The mutant human b-glucuronidase may also be used to improve enzyme replacement therapy of b-glucuronidase deficient patients.

Compared to other enzymes employed for antibody-directed enzyme prodrug therapy, our enzyme displays high activity and low immunogenicity. Most prodrug-activating enzymes are derived from bacteria or viruses, which causes immune responses in humans so multiple administrations cannot be given.

Conclusion

A mutant b-glucuronidase enzyme has been produced for use in cancer therapy and enzyme replacement therapy.

Relevance/Opportunity

Please enquire quoting reference no. 12A-970630 regarding licensing or codevelopment partnerships.

Preclinical

US Provisional pending