A Polyamine Oxidizing Enzyme as a Drug to Treat Breast Cancer
Final rept. 20 Jun 2005-19 Jun 2009
NORTHERN CALIFORNIA INST FOR RESEARCH AND EDUCATION SAN FRANCISCO
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Work was initiated to test two polyethylene glycolated PEGylated forms of bovine serum amine oxidase SAO as effective treatments for breast cancer using a mouse model. Hopefully, this approach, or a variation thereof, could be used as a new a therapy for breast and other human cancers. Currently, a large quantity of pure bovine SAO is in hand, which was obtained from 10 gallons of fresh cow blood. A final purification step was used to produce large quantities of extremely pure SAO. Attempts to find a cost-effective, practical method for the degycosylation of SAO were unsuccessful. Using different PEGylating reagents, we attempted to obtain several PEG derivatives of SAO. Although preliminary test indicated that SAO could be PEGylated at a fairly high level, efforts to repeat this on a large scale failed. Hence, it has not been possible to test any PEG-SAO derivatives in non-tumorigenic mice, or mice harboring human breast-cancer tumors. Effort to find efficient ways to PEGylate SAO at a high level will continue. High level PEGylation occurred with freshly prepared SAO. Although about 3 grams of highly pure enzyme, it is proposed that freshly prepared oxidase is required. In the future, will carry out smaller scale purifications, and only use the freshly prepared SAO for PEGylation, we will try different PEGylation reagents. Hopefully, the problem can be remedied.
- Medicine and Medical Research