Method of hematopoietic stem cell transplants
The present disclosure provides distinct therapeutic populations of cells that form a pharmaceutical composition useful in hematopoietic stem/progenitor cell transplant. For example, the present disclosure provides a therapeutic population of cells, comprising an enriched population of hematopoietic stem/progenitor cells, memory T cells, regulatory T cells, and wherein the population of cells is depleted of naïve conventional αβ-T cells. The present disclosure further provides methods of treatment using the therapeutic population of cells. In other embodiments, the present disclosure provides methods of producing a therapeutic population of cells.
1. A method for producing a therapeutic composition comprising the steps of enriching from a biological sample:
a. hematopoietic stem and progenitor cells (HSPCs);
b. memory T cells (Tmems);
c. regulatory T cells (Tregs); and
further comprising depleting from the sample naïve conventional aβ-T cells to produce the therapeutic composition wherein 2% or fewer of the cells in the composition are naïve conventional αβ-T cells.
2. The method of claim 1 , further comprising enriching iNKT cells from the biological sample.
3. The method of claim 2 , wherein the ratio of naïve conventional αβ-T cells to iNKT is less than 100:1.
4. The method of claim 2 , wherein iNKT cells are CD3 + Va24Ja18 + CD1d-tetramer + .
5. The method of claim 1 , wherein the HSPCs are CD34 + .
6. The method of claim 1 , wherein the Tmems are CD3 + CD45RA − CD45R0 + .
7. The method of claim 1 , wherein the Tregs are CD4 + CD25 + CD127 −/lo .
8. The method of claim 1 , wherein the naïve conventional αβ-T cells are CD45RA + CD25 − .
9. The method of claim 1 , wherein said enriching comprises density separation, tetrameric antibody complex mediated sorting, magnetic activated cell sorting, multiparameter fluorescence-based cell sorting, or any combination thereof.
10. The method of claim 1 , further comprising adding a pharmaceutically acceptable excipient to the composition.
11. The method of claim 10 , wherein the excipient is a saline solution and/or human serum.
12. The method of claim 1 , wherein the biological sample is depleted of naïve conventional αβ-T cells to comprise less than 0.5% naïve conventional αβ-T cells.
13. The method of claim 1 , wherein the biological sample is selected from mobilized peripheral blood, a mobilized apheresis product, bone marrow, umbilical cord blood, non-mobilized blood, non-mobilized apheresis product, peripheral blood mononuclear cells, or any combination thereof.