Application

A prokaryotic manufacturing process for efficient production of recombinant GIFT (GM-CSF & Interleukin Fusion Transgene) fusion cytokines as well as other recombinant therapeutics.

Key Benefits

• Production via bacterial and yeast expression increases yield 1000 fold compared to mammalian systems while also decreasing cost and complexity.
• GIFTs expressed in bacteria retain the biological activity of their mammalian expressed counterparts.

Market Summary

Biologic therapeutics is a rapidly growing class of treatments. Composed of proteins expressed in recombinant systems, biologics are often difficult and expensive to produce efficiently. Due to the complexity of manufacturing, biologics can cost tens of thousands of dollars per year for treatment. Optimized manufacturing processes allow for improved scalability, decreased production costs, and may also decrease the development timeline for new biologics.

Technical Summary

GIFT fusokines are fusion cytokine proteins that have powerful immuno-modulatory effects. In general, GIFT proteins are fusions between granulocyte macrophage-colony stimulating factor (GM-CSF) and an interleukin that exhibit unique effects on cells of the immune system. These effects are often distinctly different from and in addition to the function of the parent molecules. Depending upon the combination, GIFTs have potential applications in a wide variety of indications such as cancer, vaccine adjuvants, and immunosupressants.

Expression of GIFT fusokines in mammalian cells is a process that is costly, somewhat complex, and relatively inefficient. To address these challenges, Emory investigators have developed optimized manufacturing processes in yeast or bacterial systems. Using these manufacturing processes, GIFT yield is up to 1000 fold higher (1 mg/L) than from comparable volumes of mammalian culture. Bacterially manufactured fusokine proteins appear to retain the tertiary structure, solubility, and biological activity of their mammalian expressed counterparts.

Developmental Stage

• Bacterial manufacturing process has been validated for GIFT15; GIFT15 produced via this process retains its biologic functions.
• Yeast manufacturing process has been validated for rGIFT4
• Work is underway to replicate this process for other GIFT molecules (GIFT7, & GIFT9).

Publications

Rafei, M. et al. (2007). Blood, 109(5), 2234-42.
Rafei, M. et al. (2009). Nature Medicine, 15(9), 1038-45.
Rafei, M. et al. (2009). Immunotherapy, 1(6), 913-5.