Tumor Targeting and Prodrug Lab

Research Discription    

The major interest of our laboratory is the development of novel targeting strategies for cancer therapy. We have previously developed potent antitumor agents by conjugating toxins, drugs or isotopes to tumor-specific monoclonal antibodies. We have designed and synthesized glucuronide prodrugs that can be enzymatically converted to antineoplastic agents by beta-glucuronidase. These prodrugs are preferentially activated at tumor cells after beta-glucuronidase is first targeted to these cells as an antibody-enzyme conjugate that can specifically bind to tumor cells (Fig. 1). Conjugate treatment followed by prodrug administration resulted in complete eradication of malignant hepatoma ascites in rats and hepatoma xenografts in nude mice. Defined antibody-enzyme fusion proteins and novel glucuronide prodrugs are currently under development. These strategies show promise for increasing the specificity and efficacy of chemotherapy.

We are also developing novel strategies for gene-mediated cancer therapy based on the expression of therapeutic proteins on the surface of tumor cells. Potential proteins for surface expression include prodrug-activating enzymes, single-chain antibodies, cytokines and superantigens.

We have generated anti-PEG monoclonal antibodies that can be employed to detect and measure pegylated proteins and compounds.

More information about these antibodies can be found here: ANTI-PEG

References on these topics and related research on tumor targeting by other authors can be found by following these links.

GO TO THE ANTI-PEG WEBSITE