Human facilitating cells
View Patent ↗The present disclosure relates to human facilitating cells (hFC), and methods of isolating, characterizing, and using such hFCs.
1. A method of making a therapeutic human cellular composition from a donor for delivery to a recipient that is not HLA-identical to the donor, comprising the steps of:
providing a donor source of human hematopoietic stem cells (HSCs);
depleting alpha beta TCR + T cells without significantly depleting HSCs or facilitating cells (FCs) from said donor source to produce a T cell-depleted donor source;
adjusting the number of alpha beta TCR + T cells in said T cell-depleted donor source to between about 2.0×10 6 and about 5.0×10 6 alpha beta TCR + T cells per kg recipient body weight,
thereby producing a therapeutic human cellular composition from a donor for delivery to a recipient that is not HLA-identical to the donor.
2. The method of claim 1 , wherein the source of human HSCs is bone marrow, thymus, peripheral blood, fetal liver, or embryonic yolk sac.
3. The method of claim 1 , wherein the source of human HSCs is bone marrow.
4. The method of claim 1 , wherein the cells are depleted using one or more antibodies.
5. The method of claim 4 , wherein the one or more antibodies are conjugated to magnetic beads.
6. The method of claim 1 , wherein the therapeutic human cellular composition improves the engraftment ability of the human HSCs compared to human HSCs engrafted alone or in the absence of the therapeutic human cellular composition.
7. The method of claim 1 , wherein the number of alpha beta TCR + T cells are adjusted to between about 3.0×10 6 and about 4.2×10 6 alpha beta TCR + T cells/kg recipient body weight.
8. The method of claim 1 , wherein the number of alpha beta TCR + T cells are adjusted to about 3 0.2×10 6 alpha beta TCR + T cells per kilogram of the recipient's body weight.
9. The method of claim 1 , wherein the number of alpha beta TCR + T cells are adjusted to about 3.8×10 6 alpha beta TCR + T cells per kilogram of the recipient's body weight.
10. A method of making a therapeutic human cellular composition from a donor for delivery to a recipient that is not HLA-identical to the donor, comprising the steps of:
providing a donor source of human hematopoietic stem cells (HSCs);
depleting alpha beta TCR + T cells without significantly depleting HSCs or facilitating cells (FCs) from said donor source to produce a T cell-depleted donor source;
adjusting the number of alpha beta TCR + T cells in said T cell-depleted donor source to greater than 2.0×10 6 alpha beta TCR + T cells per kg recipient body weight up to a maximal dose at which stable engraftment is achieved without GVHD,
thereby producing a therapeutic human cellular composition for delivery to a recipient that is not HLA-identical to the donor.