Compositions 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 pharmaceutical composition comprising one or more unit doses of a cellular graft, wherein each unit dose of the cellular graft comprises populations of therapeutic cells for each kilogram (kg) of body weight of a subject receiving the cellular graft, and wherein the populations of therapeutic cells of each unit dose comprise:
more than 3×10 5 hematopoietic stem/progenitor cells (HSPC) per kilogram of body weight of the subject receiving the cellular graft,
more than 3×10 5 memory T cells (Tmem) per kilogram of body weight of the subject receiving the cellular graft,
more than 5×10 5 regulatory T cells (Treg) per kilogram of body weight of the subject receiving the cellular graft, and
less than 3×10 5 nave conventional αβ-T cells per kilogram of body weight of the subject receiving the cellular graft.
2. The pharmaceutical composition of claim 1 , wherein the unit dose further comprises 0.5×10 3 to 2000×10 3 invariant natural killer T (iNKT) cells per kilogram of body weight of the subject receiving the cellular graft.
3. The pharmaceutical composition of claim 1 , wherein the HSPC are CD34 + , the Tmem are CD3 + CD45RA − CD45RO + , the Treg are CD4 + CD25 + CD127 −/lo , CD45RA + , or a combination thereof, and the nave conventional αβ-T cells are CD3 + CD45RA + CD25 − TCR Va24Ja18 − .
4. The pharmaceutical composition of claim 2 , wherein the iNKT are CD3 + Vα24Jα18 + .
5. The pharmaceutical composition of claim 1 , wherein the populations of therapeutic cells of each unit dose comprise:
1.0×10 6 to 50×10 6 HSPC per kilogram of body weight of the subject receiving the cellular graft,
0.3×10 6 to 1000×10 6 Tmem per kilogram of body weight of the subject receiving the cellular graft,
0.5×10 6 to 1000×10 6 Treg per kilogram of body weight of the subject receiving the cellular graft, and
less than 3×10 5 naïve conventional αβ-T cells per kilogram of body weight of the subject receiving the cellular graft.
6. The pharmaceutical composition of claim 1 , wherein the unit dose further comprises iNKT cells, wherein the populations of therapeutic cells of each unit dose comprise:
1.0×10 6 to 50×10 6 HSPC per kilogram of body weight of the subject receiving the cellular graft,
0.3×10 6 to 1000×10 6 Tmem per kilogram of body weight of the subject receiving the cellular graft,
0.5×10 6 to 1000×10 6 Treg per kilogram of body weight of the subject receiving the cellular graft,
0.5×10 3 to 2000×10 3 iNKT per kilogram of body weight of the subject receiving the cellular graft, and
less than 3×10 5 naïve conventional αβ-T cells per kilogram of body weight of the subject receiving the cellular graft.
7. The pharmaceutical composition of claim 1 , wherein the populations of therapeutic cells of each unit dose comprises 0.2×10 6 to 500×10 6 naive Treg cells per kilogram of body weight of the subject receiving the cellular graft.
8. The pharmaceutical composition of claim 2 , wherein the populations of therapeutic cells of each unit dose comprises 0.2×10 6 to 500×10 6 naive Treg cells per kilogram of body weight of the subject receiving the cellular graft.
9. The pharmaceutical composition of claim 1 , wherein the populations of therapeutic cells of each unit dose comprises 1.0×10 6 to 50×10 6 HSPC per kilogram of body weight of the subject receiving the cellular graft.
10. The pharmaceutical composition of claim 1 , wherein the populations of therapeutic cells of each unit dose comprises 1.0×10 6 to 250×10 6 Tmem per kilogram of body weight of the subject receiving the cellular graft.
11. The pharmaceutical composition of claim 1 , wherein the populations of therapeutic cells of each unit dose comprises less than 1×10 5 naïve conventional αβ-T cells per kilogram of body weight of the subject receiving the cellular graft.
12. The pharmaceutical composition of claim 1 , wherein the populations of therapeutic cells of each unit dose comprises 1×10 6 to 2.5×10 6 Treg cells per kilogram of body weight of the subject receiving the cellular graft.
13. The pharmaceutical composition of claim 1 , wherein the unit dose further comprises 1×10 4 to 200×10 4 iNKT per kilogram of body weight of the subject receiving the cellular graft.
14. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition is suitable for administration to the subject receiving the cellular graft.
15. The pharmaceutical composition of claim 14 , further comprising an excipient.
16. The pharmaceutical composition of claim 15 , wherein the excipient is Normosol-R.
17. The pharmaceutical composition of claim 15 , wherein the excipient is human serum.
18. The pharmaceutical composition of claim 14 , wherein the HSPC are haploidentical to the subject receiving the cellular graft.
19. The pharmaceutical composition of claim 14 , wherein the Treg, Tmem, or a combination thereof are HLA matched with the subject receiving the cellular graft.
20. The pharmaceutical composition of claim 14 , wherein at least a portion of the populations of therapeutic cells are autologous to the subject receiving the cellular graft.
21. A pharmaceutical composition comprising a population of therapeutic cells that is enriched for hematopoietic stem/progenitor cells (HSPC), memory T cells (Tmem), and regulatory T cells (Treg), and wherein the population of cells is depleted of naïve conventional αβ-T cells, wherein the population of therapeutic cells comprises a ratio of naive conventional αβ-T cells to HSPC that is less than 1:400, a ratio of naïve conventional αβ-T cells to Tmem less than 1:800, and a ratio of naïve conventional αβ-T cells to Treg less than 1:5.
22. The pharmaceutical composition of claim 21 , wherein the population of therapeutic cells further comprises invariant Natural Killer T cells (iNKT) and the population of therapeutic cells comprises a ratio of naïve conventional αβ-T cells to iNKT less than 100:1.
23. The pharmaceutical composition of claim 21 , wherein the ratio of naïve conventional αβ-T cells to Tmem is less than 1:3.
24. The pharmaceutical composition of claim 21 , wherein the population of therapeutic cells comprises a ratio of naïve conventional αβ-T cells to naïve Treg less than 1:2.