The Approach
NK cells do not require the same level of targeting specificity as other immune cells, such as T cells, making them an advantageous therapeutic agent. NK cells can recognize non-specific inflammatory signals released in the region of the tumor, extravasate the blood, and infiltrate the tumor microenvironment. Once the NK cells have entered the diseased tissue, cell contact triggers a cytotoxic response from the NK cells to clear the tumor cells. Because the NK cells do not contain Class II MHC and therefore do not invoke an immune response, NK cell therapies can be used allogeneically without the requirement of gene-editing.
The Challenge
NK cells must be expanded ex vivo to deliver a clinically significant dose, and most NK cell expansion processes require feeder cells or other exogenous stimulators, making this a primary challenge in manufacturing GMP-grade NK cell therapies. NK cells are also often outgrown by T cells in culture, resulting in a product unfit for allogeneic use. Upholding the integrity of the complex NK cell phenotype during expansion is imperative to the successful manufacturing of a NK cell therapy that maintains the cells’ innate immune response.
Theragent’s expertise in NK cell biology and immune
response supports the appropriate assay development for validation of the manufacturing process.
The ability of NK cells to extravasate blood into non-specific tumor regions has prompted their use in solid tumor immuno-oncology therapies, including non-small cell lung cancer, glioma, melanoma, and gastric cancer.
At Theragent, we have developed and optimized protocols to expand NK cells ex vivo. We have optimized a variety of parameters, including cell culture media and supplement formulations, culture time and conditions, and various exogenous stimuli to regulate their proliferation and cytotoxic potential. Following expansion, understanding the homing and migration capacity of the NK cells is a critical step, but one that is often not accomplished due to lack of applicable protocols. Theragent’s expertise in NK cell biology and in monitoring the immune response supports the appropriate assay development for demonstration of manufacturing success by linking the expansion process to cellular function.
Connect with our team to learn more about our NK cell know-how.