CBE Seminar: James R. Swartz

“Opening Microbial Cells Expands Their Potential”

This talk will explain how multiple advances in the technology for cell-free protein synthesis (CFPS) may be on the verge of expanding the biopharmaceutical industry.

The era of rRNA biopharmaceuticals was launched using E.coli in the early 1980’s to produce proteins such as human insulin (Eli Lilly), human growth hormone (Genentech), granulocyte colony stimulating factor (Amgen), and alpha-interferon (Genentech and Roche). However, as the complexity of the protein pharmaceuticals increased, the industry turned to eukaryotic cells to provide more complex disulfide bond patterns and glycosylation for products such as erythropoietin (Amgen) and tissue-plasminogen activator (Genentech). Further driven by the emergence of monoclonal antibodies as a large family of potent and versatile pharmaceuticals, CHO cells then emerged as the dominant production platform.

Ironically, the need for even more complexity and precision may now be motivating a shift back to prokaryotic systems. Sutro Biopharma, independently and in collaboration with Celgene and Merck Serono, is now developing a new class of antibody drug conjugates (ADCs) produced using E.coli cell extracts. They have established GMP manufacturing capability and are nearly ready for human trials. CFPS is providing direct access to the protein synthesis reaction chamber, and that allows the spatially precise introduction of uniquely reactive, non-natural amino acids. This, in turn, enables the precise localization of an exact number of drug molecules per antibody.  It also speeds up the production and screening of many ADC candidates so that safety and efficacy can be more effectively optimized. While the jury is still out, such products may be the wave of the future.

This presentation will summarize the technology foundation being used by Sutro. It will then go on to describe how the capabilities of this platform are being further expanded so even more complex pharmaceutical targets can be approached. As an example, the development of highly potent, modular vaccines and novel drug delivery vehicles will be described. Both are based on a multiply-modified Virus-like Particle (VLP) derived from the core protein capsid of the hepatitis B virus. Both pursuits rely upon the versatility offered by CFPS.

Dr. Swartz obtained his BS in chemical engineering from South Dakota School of Mines and Technology.  After working two years for Union Oil Co. of California, he earned his M.S. in chemical engineering and D.Sc. in biochemical engineering at MIT. Following a scientific exchange visit to the U.S.S.R. and an initial research position at Eli Lilly and Co., he joined Genentech in 1981, where he served in both scientific and managerial positions related to rDNA protein production and protein pharmaceutical development for nearly 18 years.

In 1998, he moved to Stanford University as Professor of Chemical Engineering focusing on cell-free biology. In 1999, he was elected to the National Academy of Engineering, and, in 2003, helped initiate Stanford’s new Department of Bioengineering.  He was named the Leland T. Edwards Professor in the School of Engineering in 2006 and the James H. Clark Professor in 2009.  He is a founder of Sutro Biopharma, Inc., dedicated to developing cell-free protein pharmaceutical technologies and of GreenLight Biosciences, a cell-free metabolic engineering company His research seeks to reproduce and direct complex metabolism in a cell-free environment. Current applications include improved vaccine architectures, new cancer diagnostics, targeted drug and nucleic acid delivery, and biological hydrogen production from sunlight and biomass.

Seminar Flyer_James R. Swartz