Abstract

Bioproduction and Clinical Translation of Extracellular Vesicles for Treatment of Inflammatory Diseases

Marcin Jurga, R&D Manager, The Cell Factory (Esperite)

Recent progress in development of experimental cell-based therapies demonstrated a promising efficacy of somatic cells in stimulation and modulation of tissue’s regenerative capabilities. Commercialization of cell therapeutics remains challenging mainly due to complex and expensive production process. It has been demonstrated that extracellular vesicles (EVs) could be an attractive alternative for many allogenic cell-based therapeutics. EVs are nanometer-size particles secreted by different types of cells in vivo and in vitro. EVs are presenting a similar therapeutic properties to the parent cells with several additional benefits: (i) manufacturing is more effective and cheaper, (ii) higher stability, (iii) lower immunogenicity, (iv) no risk of uncontrolled ectopic differentiation and proliferation, (v) better penetration into injury site e.g. cross BBB.
 
The Cell Factory has developed a GMP-compliant production process of the clinical-grade MSC-EVs using scalable 3D bioreactor systems. The main differentiator of our technology is use of fully-defined culture media, no research-grade products, no FBS, sera or platelet lysates during entire production process. This provides the highest purity and quality of the MSC-EVs and the batch-to-batch reproducibility.    

Currently, our company in collaboration with the academic and clinical partners from Bambino Gesù Children's Hospital, Mario Negri Institute for Pharmacological Research and the Women’s and Children’s Health Department of the University of Padua are developing the EVs drug products: CF-MEV-107 for treatment of drug resistant fistulas in Crohn’s diseases and CF-MEV-117 for drug resistant epilepsy in children. The main activities of the MSC-EVs are inhibition of inflammation and immunomodulation what have been demonstrated in many disease models. Anti-inflammatory activity of MSC-EVs has been demonstrated in various assays e.g. MSC-EVs inhibits B cells proliferation and differentiation in co-cultures with CpG-activated peripheral blood mononucleated cells (PBMC). In similar assay MSC-EVs increase Treg cells proliferation and apoptosis and secretion of IL10 upon PBMC stimulation with anti-CD3/CD28.

We are expecting that MSC-EVs will provide a more effective, accessible and affordable alternative for many allogenic stem cell in the near future.