dc.contributor.author
Wiesinger, Manuel
dc.contributor.author
Stoica, Diane
dc.contributor.author
Roessner, Susanne
dc.contributor.author
Lorenz, Carmen
dc.contributor.author
Fischer, Anika
dc.contributor.author
Atreya, Raja
dc.contributor.author
Neufert, Clemens F.
dc.contributor.author
Atreya, Imke
dc.contributor.author
Scheffold, Alexander
dc.contributor.author
Schuler-Thurner, Beatrice
dc.contributor.author
Neurath, Markus F.
dc.contributor.author
Schuler, Gerold
dc.contributor.author
Voskens, Caroline J.
dc.date.accessioned
2018-06-08T10:18:47Z
dc.date.available
2017-11-20T12:54:30.135Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/20230
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-23535
dc.description.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 vivo expansion 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 of ex vivo expanded 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, are ex vivo expanded 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.
en
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.subject
regulatory T cell
dc.subject
good manufacturing practice
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit
dc.title
Good Manufacturing Practice-Compliant Production and Lot-Release of Ex Vivo
Expanded Regulatory T Cells As Basis for Treatment of Patients with Autoimmune
and Inflammatory Disorders
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation
Front. Immunol. - 8 (2017), Artikel Nr. 1371
dcterms.bibliographicCitation.doi
10.3389/fimmu.2017.01371
dcterms.bibliographicCitation.url
http://doi.org/10.3389/fimmu.2017.01371
refubium.affiliation
Charité - Universitätsmedizin Berlin
de
refubium.mycore.fudocsId
FUDOCS_document_000000028506
refubium.note.author
Der Artikel wurde in einer reinen Open-Access-Zeitschrift publiziert.
refubium.resourceType.isindependentpub
no
refubium.mycore.derivateId
FUDOCS_derivate_000000009131
dcterms.accessRights.openaire
open access