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Clinical Grade Manufacturing of Human Alloantigen‐Reactive Regulatory T Cells for Use in Transplantation
Author(s) -
Putnam A. L.,
Safinia N.,
Medvec A.,
Laszkowska M.,
Wray M.,
Mintz M. A.,
Trotta E.,
Szot G. L.,
Liu W.,
Lares A.,
Lee K.,
Laing A.,
Lechler R. I.,
Riley J. L.,
Bluestone J. A.,
Lombardi G.,
Tang Q.
Publication year - 2013
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/ajt.12433
Subject(s) - medicine , transplantation , immunosuppression , immunology , in vitro , polyclonal antibodies , antigen , biology , surgery , biochemistry
Regulatory T cell (Treg) therapy has the potential to induce transplantation tolerance so that immunosuppression and associated morbidity can be minimized. Alloantigen‐reactive Tregs (arTregs) are more effective at preventing graft rejection than polyclonally expanded Tregs (PolyTregs) in murine models. We have developed a manufacturing process to expand human arTregs in short‐term cultures using good manufacturing practice‐compliant reagents. This process uses CD40L‐activated allogeneic B cells to selectively expand arTregs followed by polyclonal restimulation to increase yield. Tregs expanded 100‐ to 1600‐fold were highly alloantigen reactive and expressed the phenotype of stable Tregs. The alloantigen‐expanded Tregs had a diverse TCR repertoire. They were more potent than PolyTregs in vitro and more effective at controlling allograft injuries in vivo in a humanized mouse model.