A novel method based on nontoxic components for targeting cancerous tissue is proposed. A binary system comprised of glucose oxidase and a metalloporphyrin conjugated to separate monoclonal antibodies (MAb) is targeted to a diseased cell. The juxtaposition of these components on the cell surface allows a cascade of actions to occur that ultimately kill the targeted cell.Glucose oxidase generates hydrogen peroxide from extracellular glucose and oxygen; the peroxide is activated into a reactive oxy intermediate by the metalloporphyrin. These intermediates react irreversibly with nearby biomolecules, such as cell membrane walls, which will destroy the cell. As this system is based on two catalytic components, combining a small amount of each compound will result in an amplified effect in the microenvironment of the cancerous tissue. Moreover, deleterious side effects in vivo due to high concentrations of chemotherapeutic agent will be reduced. In addition both enzyme and metalloporphyrin are nontoxic when kept separate, therefore nonspecific binding of a MAb conjugate will not damage healthy tissue. Initial studies will utilize lectins as the affinity carriers to show the viability of the proposed system; subsequent experiments will be carried out with MAbs.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Small Business Innovation Research Grants (SBIR) - Phase I (R43)
Project #
1R43CA056212-01
Application #
3493000
Study Section
Experimental Therapeutics Subcommittee 1 (ET)
Project Start
1992-03-11
Project End
1992-08-30
Budget Start
1992-03-11
Budget End
1992-08-30
Support Year
1
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Symbiotech, Inc.
Department
Type
DUNS #
City
Wallingford
State
CT
Country
United States
Zip Code
06492