Abstract

Production of Functionally Bioactive EVs from an Immortalized Human Neural Stem Cell (hNSC) Line

Randolph Corteling, Head, ReNeuron Limited

To ensure the scale required for clinical research and development, producer cell immortalization and clonal isolation is a practical strategy to produce consistent, functionally bioactive exosomes for use as therapeutic agents. Immortalization ensures production stability and reduces the need for equivalence testing. CTX0E03 is a conditionally immortalised human neural stem cell line which has been manufactured to GMP using a 3-tier banking strategy (MCB, WCB and drug substance (DS) lots) and is currently in Phase II clinical evaluation for disability after stroke. Using the conditioned media produced during GMP manufacture, we have shown that the cell line is an abundant producer of exosomes which can be readily isolated and purified at scale using tangential flow filtration (TFF). This exosome product exhibits many of the functions attributed to the cells, is well tolerated in vivo and has demonstrated efficacy (inhibition of growth and migration of cells) in pre-clinical models of glioma.