The group led by Dr. George Georgiou developed the new antibody-production approach to improve upon processes used previously to identify new drugs. Drug companies have used those more time- and labor-intensive processes to develop antibodies for treating rheumatoid arthritis, cancer and other diseases.
The new approach developed in collaboration with Dr. Brent Iverson overcomes those obstacles, and has other advantages.
"Our approach can provide a significant time savings," said Georgiou, "and it enables antibodies to be isolated to treat human diseases that may not be possible to obtain otherwise."
The results were published online Sunday, April 15, in Nature Biotechnology.
Bacteria are easy to grow in an inexpensive broth. As a result, harmless forms of the bacterium E. coli have already been used as factories to produce antibodies (protective proteins of the human body that fight viruses, cancer cells and other harmful agents). However, previous approaches required an antibody that looked promising to be transferred from bacteria to mammalian cells to pursue large-scale, commercial production.
Getting mammalian cells to produce lots of antibodies costs more, and can take several months. The direct bacterial approach developed by the laboratory of the professor of chemical engineering, biomedical engineering, and molecular genetics and microbiology shaves weeks off the production process. Based on the method's early success, Georgiou has begun a collaboration to identify antibodies to treat arthritis and asthma.
In Georgiou's E-clonal antibody method, an antibody that is produced by an E. coli bacterium becomes tethered to one of its inner surfaces, or membranes. Small "errors" in the genes that produce antibodies are introduced. These changes result in slightly altered antibodies that may attach more strongly to a disease protein. The interaction between the antibody and the disease protein blocks the protein from doing harm in the body, effectively short-cutting a disease process.
Georgiou, who holds the Cockrell Family Regents Chair in Engineering #9, and Chemistry and Biochemistry Professor Brent Iverson, the Warren J. and Viola Mae Raymer Professor and Distinguished Teaching Professor, previously used the antibody evolution process to engineer a similar antibody that is in late-stage, clinical trials to treat human anthrax infections. Iverson is a co-author and a collaborator on the latest research.
To test the bacterium-only system, lead author Yariv Mazor, a postdoctoral student in chemical engineering, engineered antibodies to an anthrax toxin called PA. He and Thomas Van Blarcom, a graduate student in chemical engineering, used a method called APEx, co-developed by Georgiou and Iverson's lab, to identify the bacteria-bound antibodies that attach best to the PA. Van Blarcom then took those bacteria and grew large numbers of them to begin refining the steps needed for mass-scale production of promising therapeutic antibodies.