Precise delivery of treatments through antibody drug conjugates has opened the door for targeted therapies, especially in the case of chemotherapeutics. Chemists at Rice University have designed a method that could make development of antibody drug conjugates easier. The key is in adding rhodium, a rare transition metal, to the process.
This new design will enable researchers to test the function of a variety of antibody sources and antigen targets to see which will work best on a tumor cell.
In this design, the rhodium-bound protein acts as a link between the base of the antibody and the therapeutic agent. The three rhodium complexes attach to specific sites of a protein that binds to the Fc antibody region. This peptide then catalyzes site-specific attachment of therapeutic agents with minimal disruption to the antibody itself. The complexes were tested on breast cancer cells thus confirming that the modified antibodies were still able to bind to antigens.
"The beauty of this catalyst is that it binds to the constant region of the antibody, so it should be broadly general for all human antibodies," said Ball, an associate professor of chemistry and director of Rice's Institute of Biosciences and Bioengineering. "We have a single, universal cassette system that plugs into antibodies to make drug conjugates fairly quickly and easily."
The rhodium complexes play multiple roles, at least one helps orient the system properly and the second does the bond-forming chemistry.
Not only does this technique simplify the process of creating antibody drug conjugates, the authors note that it may be desirable from a regulatory perspective as well. The researchers hope to start working with clinicians and drug development researchers to test applications of these conjugates.
Image: Rice University graduate student Jun Ohata transfers a sample of a multimetallic protein. The plug-in protein is designed to simplify the task of making targeted antibody therapies. Image courtesy of Jeff Fitlow/Rice University