Clinical grade production of IL-10 producing regulatory Tr1 lymphocytes for cell therapy of chronic inflammatory diseases.
IL-10 producing regulatory type 1 (Tr1) cells represents a subpopulation of CD4(+) regulatory cells able to prevent in vitro bystander T-cell proliferation and to cure ongoing chronic colitis in mice. In order to assess the efficacy and tolerance of Tr1 cell therapy in a Phase I/IIa clinical trial in patients displaying severe Crohn's disease, we set up a reproducible manufacturing process for the GMP production of human ovalbumin specific Tr1 cells. Procedures used for Tr1-cell production include the use of Drosophila derived artificial Antigen Presenting Cells transfected with specific stimulatory molecules. Characterization of the human cell therapy product shows an in vitro suppressive activity on T-cell proliferation dependent on the production of both IL-10 and TGF-beta. Manufactured Tr1 cells display a regulatory phenotype including Foxp3, GITR and CTLA-4 surface expression. In vitro toxicity studies of human Tr1 cell product show a safety profile compatible with the use of these regulatory Tr1 lymphocytes for cell therapy.
Brun
Valérie
V
TxCell, SA, Allée de la Nertière, les Cardoulines HT1, Valbonne, France.
Bastian
Hervé
H
Neveu
Virginie
V
Foussat
Arnaud
A
D000818:Animals; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism*; D049109:Cell Proliferation; D002985:Clinical Protocols; D002999:Clone Cells; D003424:Crohn Disease / Q000276:immunology* / Q000628:therapy*; D016207:Cytokines / Q000378:metabolism; D004330:Drosophila; D006801:Humans; D016130:Immunophenotyping; D016219:Immunotherapy, Adoptive; D007621:Karyotyping; D051379:Mice; D010047:Ovalbumin; D037182:T-Cell Antigen Receptor Specificity / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
D015703:Antigens, CD; D016207:Cytokines; D010047:Ovalbumin