Abstract

An Exosome-based Drug Delivery Platform Derived From an Immortalized Human Neural Stem Cell (hNSC) Line

Randolph Corteling, Head, ReNeuron Limited

To ensure the scale required for clinical research and commercialisation producer cell immortalisation and clonal isolation is a practical strategy to produce consistent, functionally bioactive exosomes for use as therapeutic agents. Immortalisation ensures production stability and reduces the need for equivalence testing.

CTX0E03 is a conditionally immortalised human neural stem cell line that has been manufactured to clinical-grade (GMP) standards, using a 3-tier banking strategy and is currently in Phase IIb clinical evaluation for disability after stroke. Using the conditioned media produced during GMP manufacture, we have shown that CTX0E03 is an abundant producer of exosomes that can be readily isolated and purified at scale. The CTX cell line can also be rapidly and efficiently modified to direct the expression of a variety of cargoes within the secreted EV population, whilst maintaining the key immortalised stem cell characteristics of the parental cell line.  The natural tissue tropism of CTX-derived exosomes can then be exploited to deliver loaded cargoes to target cells.