Chinese Hamster Ovary (CHO) cells are the most common host platform for producing antibodies. While there is widespread adoption of this platform, there remain limitations to the use of CHO cells in certain applications, in particular to produce antibodies at large scale to combat infectious diseases:
Using a C1 Protein Production Platform (a Thermophilici Filamentous Fungus Thermothelomyces heterothallica based platform), Dyadic International, Inc. demonstrated the use of a new platform for rapid engineering of product strains to produce a COVID-19 targeted antibody and a monoclonal antibody used as a standard for comparability. Dyadic benchmarked the C1 Protein Production Platform performance in comparison to CHO and other fungal expression systems in terms of speed of development and certain product quality attributes.
As part of the solution, once antibody gene sequences are received, the team:
Benchmark the innovative, state of the art C1 Protein Production Platform versus legacy protein production methods.
The Thermothelomyces heterthalica C1 production system has great potential for use in responding to future pandemics because the production cell lines can be constructed quickly, and the antibodies have good productivity.
This project demonstrated a filamentous fungus C1 production platform that accelerates antibody expression and scale‑up benchmarking for drug companies, resulting in time benefits across non‑CHO protein expression.
The first fermentations were started less than 50 days after receiving the genetic material for building the expression constructs, and that about 5 g/l yields were obtained for both proteins in these very same fermentations after 6 or 7 days.
Fermentation yields were further improved with fermentation optimization and with multicopy expression achieved with CRISPR/Cas9 technology.
The highest titers for the target proteins were 8.95 g/l for NIIMBL antibody in 7 days and 7.7 g/l for NIIST mAb in 5 days after single-step affinity purification.
Emalfarb, M., Presenter, ARP-29 Prime Award 70NANB21H085 – Successful expression of RM8671 and Indevimab in the humanized C1 protein expression platform, NIIMBL National Meeting, Washington, D.C., July 28, 2022.
Emalfarb, M., Biomanufacturing Innovation Summit, Rutgers University Busch Student Center, Piscataway, New Jersey, July7-8, 2022.
Emalfarb, M., Successful expression of RM8671 and Imdevimab in the humanized C1 protein expression system, NIIMBL National Meeting. Washington, D.C., July 26-28, 2022
CEPI's initiative to explore fungal expression systems for rapid and affordable vaccine development
CEPI’s program to develop a single vaccine targeting multiple deadly diseases, incorporating C1
CEPI’s support for the development of a MERS coronavirus vaccine leveraging C1 technology
Dyadic’s C1 platform was selected as part of the European Union’s €170 million European Vaccine Hub (EVH) — a major initiative to enhance pandemic preparedness across Europe
These follow the Gates Foundation’s grant to develop low-cost monoclonal antibodies for malaria and RSV using the C1 platform:
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Dyadic International Inc
