Good Manufacturing Practice-Compliant Production and Lot-Release ofEx VivoExpanded Regulatory T Cells As Basis for Treatment of Patients with Autoimmune and Inflammatory Disorders

Wiesinger M, Stoica D, Roessner S, Lorenz C, Fischer A, Atreya R, Neufert C, Atreya I, Scheffold A, Schuler-Thurner B, Neurath M, Schuler G, Voskens CJ (2017)

Publication Type: Journal article

Publication year: 2017

Journal

Book Volume: 8

DOI: 10.3389/fimmu.2017.01371

Abstract

In recent years, the exploration of regulatory T cell (Treg)-based cellular therapy has become an attractive strategy to ameliorate inflammation and autoimmunity in various clinical settings. The main obstacle to the clinical application of Treg in human is their low number circulating in peripheral blood. Therefore,ex vivoexpansion is inevitable. Moreover, isolation of Treg bears the risk of concurrent isolation of unwanted effector cells, which may trigger or deteriorate inflammation upon adoptive Treg transfer. Here, we present a protocol for the GMP-compliant production, lot-release and validation ofex vivoexpanded Tregs for treatment of patients with autoimmune and inflammatory disorders. In the presented production protocol, large numbers of Treg, previously enriched from a leukapheresis product by using the CliniMACS®system, areex vivoexpanded in the presence of anti-CD3/anti-CD28 expander beads, exogenous IL-2 and rapamycin during 21 days. The expanded Treg drug product passed predefined lot-release criteria. These criteria include (i) sterility testing, (ii) assessment of Treg phenotype, (iii) assessment of non-Treg cellular impurities, (iv) confirmation of successful anti-CD3/anti-CD28 expander bead removal after expansion, and (v) confirmation of the biological function of the Treg product. Furthermore, the Treg drug product was shown to retain its stability and suppressive function for at least 1 year after freezing and thawing. Also, dilution of the Treg drug product in 0.9% physiological saline did not affect Treg phenotype and Treg function for up to 90 min. These data indicate that these cells are ready to use in a clinical setting in which a cell infusion time of up to 90 min can be expected. The presented production process has recently undergone on site GMP-conform evaluation and received GMP certification from the Bavarian authorities in Germany. This protocol can now be used for Treg-based therapy of various inflammatory and autoimmune disorders.

Authors with CRIS profile

Involved external institutions

Charité - Universitätsmedizin Berlin Germany (DE)

How to cite

APA:

Wiesinger, M., Stoica, D., Roessner, S., Lorenz, C., Fischer, A., Atreya, R.,... Voskens, C.J. (2017). Good Manufacturing Practice-Compliant Production and Lot-Release ofEx VivoExpanded Regulatory T Cells As Basis for Treatment of Patients with Autoimmune and Inflammatory Disorders. Frontiers in Immunology, 8. https://doi.org/10.3389/fimmu.2017.01371

MLA:

Wiesinger, Manuel, et al. "Good Manufacturing Practice-Compliant Production and Lot-Release ofEx VivoExpanded Regulatory T Cells As Basis for Treatment of Patients with Autoimmune and Inflammatory Disorders." Frontiers in Immunology 8 (2017).

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