Generation of Powerful Human Tolerogenic Dendritic Cells by Lentiviral-Mediated IL-10 Gene Transfer.

Frontiers in Immunology
Michela ComiSilvia Gregori

Abstract

The prominent role of dendritic cells (DC) in promoting tolerance and the development of methods to generate clinical grade products allowed the clinical application of tolerogenic DC (tolDC)-based therapies for controlling unwanted immune responses. We established an efficient method to generate tolerogenic human DC, producing supra-physiological levels of IL-10, by genetically engineering monocyte-derived DC with a bidirectional Lentiviral Vector (bdLV) encoding for IL-10 and a marker gene. DCIL-10 are mature DC, modulate T cell responses, promote T regulatory cells, and are phenotypically and functionally stable upon stimulation. Adoptive transfer of human DCIL-10 in a humanized mouse model dampens allogeneic T cell recall responses, while murine DCIL-10 delays acute graft-vs.-host disease in mice. Our report outlines an efficient method to transduce human myeloid cells with large-size LV and shows that stable over-expression of IL-10 generates an effective cell product for future clinical applications in the contest of allogeneic transplantation.

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Citations

Mar 13, 2021·Frontiers in Immunology·Marta FortunatoSilvia Gregori
Jun 3, 2021·International Journal of Molecular Sciences·Maria NamwanjeAmandeep Bajwa
Aug 8, 2021·International Journal of Molecular Sciences·Maaike Suuring, Aurélie Moreau
Aug 28, 2021·International Journal of Molecular Sciences·Laura PasseriSilvia Gregori

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Methods Mentioned

BETA
genetic modifications
transfection
density gradient centrifugation
Infection
flow cytometry
ELISA
bioluminescence imaging
genetic modification

Clinical Trials Mentioned

NCT02252055
NCT03726307
NCT03164265

Software Mentioned

GraphPad
FlowJo
Living Image
GraphPad Prism

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