Human progenitor t-cells
AssigneeSunnybrook Health Sciences Centre
InventorsJuan Carlos Zuniga-Pflucker, Geneve Awong, Ross La Motte-Mohs
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Abstract
Human progenitor T cells that are able to successfully engraft a murine thymus and differentiate into mature human T and NK cells are described. The human progenitor T cells have the phenotype CD34+CD7+CD 1a−CD5− or CD34+CD7+CD1a−CD5+ and are derived from human hematopoietic stem cells, embryonic stem cells and induced pluripotent stem cells by coculture with cells expressing a Notch receptor ligand (OP9-DL1 or OP9-DL4). Such cells are useful in a variety of applications including immune reconstitution, the treatment of immunodeficiencies and as carriers for genes used in gene therapy.
Claims9
1-31. (canceled)
32:
- A method of generating natural killer (NK) cells comprising a) culturing an isolated T progenitor cell having a phenotype CD34+CD7+CD5+CD1a− with IL-15 or IL-2 and b) isolating NK cells.
33:
- The method of claim 32 wherein the T progenitor cells having the phenotype CD34+CD7+CD5+CD1a− are prepared by a method comprising:
- (a) culturing stem cells or progenitor cells selected from the group consisting of hematopoietic stem cells, embryonic stem cells and induced pluripotent stem cells with stromal cells;
- and
- (b) determining the presence of CD34+CD7+CD5+CD1a− pro-T cells in the culture.
34:
- The method of claim 33 wherein the hematopoietic stem cell (HSC) is a human HSC.
35:
- The method of claim 33 wherein the stromal cells express a Notch ligand.
36:
- The method according to claim 35 wherein the Notch ligand is DL1 or DL4.
37:
- The method of claim 36 wherein the stromal cell expressing the Notch ligand is an OP-9 cell.
38:
- An isolated progenitor T cell having a phenotype CD34+CD7+CD5+CD1a−.
39:
- A pharmaceutical composition comprising an isolated progenitor T cell according to claim 38 and a pharmaceutically acceptable diluent or carrier.