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Biopharmaceutical companies across the globe are racing to bring new drugs to market, and an area of research and development that is exploding faster than most is protein-based therapeutics, which use the body’s own protein processes to design new therapies. Insulin was the first therapeutic protein to be introduced to market for the treatment of diabetes in the 1920s, and the search has been underway ever since to apply the same concept to more diseases.
The past few months have seen significant advances in the field’s promise, as two different companies have announced major breakthroughs in their ability to manufacture therapeutic proteins. A team at Chalmers University of Technology has finally mapped the metabolism of yeast cells, opening the door for mass production of critical therapies, while the UK’s Centre for Process Innovation has found a method using transgenic animals that shows remarkable promise.
Starting with the fungal angle, the Swedish Chalmers University of Technology has announced a definitive mapping of the metabolism of yeast cells, a project that took more than four years. The researchers involved chose yeast because it offers several distinct advantages as a production host—it is a fast-growing protein producer which is easy to manipulate, and which offers human-like structures that respond well to laboratory manipulation.
The production of proteins in yeast cells involves more than 100 processes and over 200 enzymes, hence the four-year process to create the comprehensive model. Yeast is currently used in the production of insulin, as well as a therapeutic human papillomavirus vaccine that may reverse cancerous infections, but using it to manufacture protein therapies for cancer, Alzheimer’s or multiple sclerosis has proven far more challenging. Antibodies to these diseases are currently being produced in a factory that uses Chinese hamster ovary (CHO) cells as the host, a process that is extremely limited and expensive. These bioreactors are associated with both low yield and solubility problems, making their output of limited use.
“Yeast is a superb modeling system. Almost everything in yeast is also found in humans. If we can get yeast cells to do the same thing [as CHOs], it will be significantly cheaper—perhaps 10 percent of what it costs today. Our vision is to eventually be able to mass-produce and supply the entire world with therapies that are too expensive for many countries today,” says Jens Nielsen, professor of systems biology at Chalmers University.
By studying yeast’s process step-by-step, the scientists also found mechanisms that can potentially make the process more efficient—and open doors to produce targeted antibodies in quantities that can really change the field of protein-based therapy.
Meanwhile, the Centre for Process Innovation (CPI), the UK’s technology innovation provider for process manufacturing, has been focused on creating therapeutic biologics in transgenic animals. Also recognizing the disadvantages of CHOs, they have been exploring options for other natural biological systems for protein exploration. Working in partnership with the University of Edinburgh’s Roslin Institute, researchers have worked with a line of genetically modified chickens able to express different recombinant proteins in their egg whites.
The Roslin Institute successfully created a transgenic chicken that expresses the CSF1-Fc protein—a protein that was subsequently found to markedly improve the immune system of pigs—in its egg white. The partnership will explore the ability to take egg white containing CSF1-Fc to determine the possibility for scaling the production to a level to be clinically useful in drug development.
According to their press release, the collaborators aim to demonstrate an economically viable and scalable downstream process to isolate this therapeutic protein in egg whites. Should the process prove viable and scalable, says CPI’s Natasha Lethbridge, “the next stage will be for Roslin Technologies to commercialize this protein for the reagents market.”
The implications for a faster, more efficient means of therapeutic protein development, whether through yeast or transgenic chickens, has the potential to fundamentally change biologic manufacturing. While the pharmaceutical process may take five to 10 years to bring something to market, the money-making potential for faster and more efficient commercial applications suggests that these breakthroughs will be welcome across the industry.