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US 9,801,911 B2Granted
Expansion of alloantigen-reactive regulatory T cells
AssigneeThe Regents of the University of California
InventorsQizhi Tang, Jeffrey A. Bluestone
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Abstract
The present disclosure relates generally to the manufacture of regulatory T cells (Tregs) for use in immunotherapy. In particular, the present disclosure relates to robust approaches for the expansion of alloantigen-reactive Tregs ex vivo. Alloantigen-reactive Tregs produced in this way are suitable for the induction and/or maintenance of immunologic tolerance in recipients of allogeneic transplants.
Claims9
A method for the production of human, donor-reactive regulatory T cells (Tregs), comprising:
- a) co-culturing CD19+ B cells of a human donor with irradiated CD40L+ human leukemia feeder cells under conditions effective in producing stimulated B cells (sBc);
- b) co-culturing CD4+, CD25+, CD127−/lo T cells isolated from peripheral blood mononuclear cells (PBMC) of a human recipient with said sBc under conditions effective in selectively expanding human donor-reactive regulatory T cells (Tregs);
- and
- c) re-stimulating said donor-reactive Tregs by cross-linking CD3 and CD28 of said donor-reactive Tregs using monoclonal antibodies under conditions effective in producing re-stimulated donor-reactive Tregs that are CD4+, Helios+ and Foxp3+,
- wherein the donor is a first human subject and the recipient is a second human subject and the donor is HLA-mismatched in relation to the human recipient.
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