Research Project
3493000
DESCRIPTION: (A dapted from the applicant's abstract) 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.
