Looking Beyond Mammals to Microbes for Tomorrow’s Drugs

(DGIwire) – In order to create the current generation of biologic drugs, manufacturers have largely depended on cell lines derived from mammals—specifically, the Chinese hamster ovary (CHO) cell. But as Mark Emalfarb, President and CEO of Dyadic International, wrote recently on TheMedicineMaker.com, it may be time to move from mammals to microbes for the next wave of biologics.

“CHO cells are used to make today’s bestselling monoclonal antibodies,” Emalfarb notes. “However, CHO cannot produce sufficient quantities of drug to satisfy the needs of the market without driving costs very high. As a result, the industry needs to look beyond the limitations and costs of CHO—in fact, perhaps beyond mammalian cell lines altogether.”

As an alternative, he believes a genetically modified form of a fungus called Myceliophthora thermophila, named C1, might have the ability to change the industry. Studies have shown that it takes about twice as long to create CHO cell lines when compared with microbial cell lines.

C1 was developed by exposing cells of this fungus to ultraviolet light to induce random mutations. Scientists then expanded and reinforced potentially beneficial mutations to drastically change the shape of the cells from long, spaghetti-like strands to short, grain-sized sections. Since C1 fungal cells secrete proteins from the ends of their filaments, the selection process resulted in more secreting ends, multiplying the potential total amount of drug that could be produced.

This, in turn, brought with it even more potential advantages. As Emalfarb notes, its distinctive shape means that C1 can be grown more easily than CHO in large tanks. Further, it offers a much shorter production time for certain drugs such as monoclonal antibodies than CHO does, and requires significantly smaller production facilities.

Emalfarb believes C1 cells could speed up the development, lower the production costs and improve the performance of biologic vaccines and drugs. Eventually, if widely adopted, C1 might supplant CHO as the go-to drug manufacturing platform, at least for some companies. He foresees a time when C1 might also enable the development and commercialization of therapeutic products that are difficult to create at reasonable quantities in CHO and other cell lines, while also being able to produce larger amounts of protein for drug discovery and development purposes as well.

“Today it is well worth examining how alternative methods of producing biologics and other drugs, such as C1, could benefit the industry and the patient population at large,” adds Emalfarb.