Low-cost Production and Purification of Cytokines and Growth Factors for Cell Therapy Products

The aim of this project is to scale-up and standardize the manufacturing of a low-cost purification medium capable of capturing large scale quantities of tagged proteins and releasing the protein pure and tag-free

Industry Need

Cytokines are proteins used in cell culture to support cell growth, survival, and differentiation.
While they are a vital component of cell therapy manufacturing, they are also the most expensive, with costs ranging from $1K to $50K for a single milligram per cytokine.
The industry would greatly benefit from a new approach to manufacture cytokines for cell growth that is more cost effective.

Approach

Focusing on IL-2 and FGF2 cytokines, Potomac Affinity Proteins teamed with the University of Maryland to scale cytokine production reliably and at a fraction of the cost. The team aimed to use Potomac Affinity Proteins’ e. Coli expression system to create a platform process for cytokine production and purification that integrates molecular machinery into traditional manufacturing technologies. The process would allow for greater scale up potential at a reduced cost, while expanding flexibility for the industry to adopt the novel purification process for other critical cytokines or proteins.

Impacts

Develop a novel low-cost purification technology to purify difficult to express tag-free proteins

In addition to the nearly 2,000% increase over expected production, the team achieved a significant cost reduction of 90% - 99.8%, from $1k - $50k per mg to less than $100 per mg. 

Reduce the cost of growth factors (by 10 fold) for cell therapy manufacturing

This basic methodology can be applied across additional cytokines beyond IL-2 and FGF2, but it also can be scaled-up to manufacture significantly higher quantities, reducing cost to only dollars per mg, potentially resulting in significant manufacturing cost savings. 

Outputs/Deliverables

Purification media was produced economically in a simple process.
Purification media was used to purify > 1 g of cytokine (IL2 or FGF2) from a 5L fermentation in a simple, one day process.
Purified IL2 and FGF2 passed all biophysical and biological validations using commercially available proteins as controls.

Publications

Bryan, P., Chen, Y., & Ruan, B., Enzymatic Purification Machines, NIIMBL National Meeting, Washington, DC, June 27, 2019.

Bryan, P., Chen, Y., Ruan, B., & Toth, E. A., Low-cost Production and Purification of Cytokines and Growth Factors for Cell Therapy Products, NIIMBL Member Forum, Virtual, July 25, 2019.

Bryan, P., Chen, Y., Ruan, B., Toth, E. A., & Simmerman, R., Fast, flexible, and economical system for affinity-tag protein purification and tag removal, NIIMBL National Meeting, Washington, DC, June 27, 2019.

Chen, Y., Bryan, P., Ruan, B., & Toth, E. A., Low-cost production and purification of cytokines and growth factors, NIIMBL National Meeting, Washington, DC, June 28, 2019.

Low-cost Production and Purification of Cytokines and Growth Factors for Cell Therapy Products (PC2.1-067), NIIMBL Member Forum, Virtual, February 26, 2021.

Low-cost Production and Purification of Cytokines and Growth Factors for Cell Therapy Products (PC2.1-067), NIIMBL Member Forum, Virtual, March 26, 2020.

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Project Lead

Potomac Affinity Proteins

Participating Organizations

University of Maryland College Park