Turning to Plant Cell Culture for Sustainability

In an effort to develop a sustainable means to manufacture a therapeutically important molecule, Agenus Inc., a Lexington, MA-based immuno-oncology company, is developing a method to produce its proprietary QS-21 Stimulon, an adjuvant used in the manufacture of vaccines, from a plant cell-culture-based process. Jennifer Buell, PhD, chief operating officer at Agenus, discussed the company’s work on developing this new process with BioPharm International.

The adjuvant

BioPharm: What is QS-21, and what role does it play in vaccine development?

Buell: QS-21 Stimulon is one of the most potent and understood adjuvants known that boosts the effectiveness of vaccines by strengthening and broadening immune responses to a vaccine’s antigens. The molecule is currently derived from a saponin extract of the Chilean soap bark tree and purified into an extract. QS-21 Stimulon is today used as a key component in GlaxoSmithKline’s (GSK) highly effective shingles vaccine, Shingrix (zoster vaccine recombinant, adjuvanted), and in the adjuvant system of the first malaria vaccine, Mosquirix (RTS,S), developed by GSK and the PATH Malaria Vaccine Initiative. This potent adjuvant is also a key component in all of Agenus’ neo-antigen vaccines.

QS-21 Stimulon significantly boosts the immune response of vaccines through multiple mechanisms described as follows:

• By inducing an influx of immune cells that interact with the vaccine’s antigens, thereby promoting adaptive immune responses.

• By inducing antibody responses. Antibodies can bind pathogens in the blood and prevent them from infecting cells.

• By inducing CD8+ T cell responses. CD8+ T cells can kill tumor cells and cells that are infected with pathogens.

• By inducing CD4+ ‘helper’ T cell responses. CD4+ T cells activate multiple tumor- and pathogen-killing mechanisms.

The molecule could also play a critical role in preventing and treating many diseases, such as herpes simplex virus, malaria, tuberculosis, influenza, ebola, anthrax, cancer, HIV, zika, lyme disease, respiratory syncytial virus, hepatitis, dengue, rotavirus, and many others.

Current process

BioPharm: How is the molecule currently produced?

Buell: The current approach to producing QS-21 from natural sources involves extracting the compound from the soap bark tree (Quillaja saponaria), an evergreen species native to Chile. 

Considering the global importance of QS-21 supply, Agenus is committed to ensuring its sustained delivery to the global vaccines market. Earlier this year, the Bill & Melinda Gates Foundation awarded Agenus a grant of approximately $1 million to develop an alternative, plant cell culture-based manufacturing process to ensure the continuous future supply of QS-21 Stimulon adjuvant. 

Alternative process

BioPharm: Where will the alternative manufacturing process be developed?

Buell: Currently, the alternative manufacturing process for QS-21 is being developed in an exclusive partnership with Phyton Biotech, which is leveraging its plant cell fermentation (PCF) technology. Phyton Biotech is attempting to demonstrate that PCF is a feasible model for the consistent, large-scale and low-cost commercial production of high-quality QS-21 directly from plant cell cultures. Together, Agenus and Phyton expect to establish an eco-friendly approach for a continuous supply of this vaccine ingredient.