Compositions and methods for hematopoietic stem cell transplantation

Abstract

The present disclosure provides distinct therapeutic cell populations that form pharmaceutical compositions useful for hematopoietic stem / progenitor cell transplantation. For example, the present disclosure provides therapeutic cell populations that include enriched populations of hematopoietic stem / progenitor cells, memory T cells, and regulatory T cells, where the cell populations are depleted of naive conventional αβ-T cells. The present disclosure further provides methods of treatment using the therapeutic cell populations. In other embodiments, the present disclosure provides methods of producing the therapeutic cell populations.

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of priority to U.S. Provisional Patent Application No. 63 / 422,375, filed November 3, 2022, and U.S. Provisional Patent Application No. 63 / 520,234, filed August 17, 2023, each of which is incorporated by reference herein in its entirety for all purposes. [Background technology]

[0002] background Myeloablative (MA) allogeneic hematopoietic cell transplantation (alloHCT) is the standard treatment for various hematologic malignancies. However, MA-alloHCT only provides curative effects in a subset of patients, and better strategies for alloHCT are still critically needed to improve patient outcomes. Summary of the Invention

[0003] overview One aspect of the present disclosure is a pharmaceutical composition comprising one or more unit doses of a cell transplant, each unit dose of the cell transplant comprising a population of therapeutic cells for each kilogram (kg) of body weight of the subject receiving the cell transplant. The population of therapeutic cells in each unit dose is 3 x 10 per kilogram of body weight of the subject receiving the cell transplant. 5 More than 3 x 10 hematopoietic stem / progenitor cells (HSPCs) per kilogram of body weight of the subject receiving the cell graft 5 More than 5 x 10 memory T cells (Tmem) per kilogram of body weight of the subject receiving the cell graft 5 regulatory T cells (Tregs) greater than 3 x 10 per kilogram of body weight of the subject receiving the cell graft 5 In this embodiment, the subject receiving the cell transplant has undergone a myeloablative conditioning regimen including thiotepa, and / or the subject receiving the cell transplant is receiving or will receive a GVHD prophylaxis regimen including tacrolimus.

[0004] In some embodiments, the unit dose is 0.5×10 per kilogram of body weight of the subject receiving the cell transplant. 3 ~2000×10 3 The cells further comprise invariant natural killer T (iNKT) cells.

[0005] In various embodiments, HSPCs are CD34+, Tmems are CD3+CD45RA-CD45RO+, Tregs are CD4+CD25+CD127- / lo, CD45RA+, or a combination thereof, and naive conventional αβ-T cells are CD3+CD45RA+CD25-TCR Va24Ja18-.

[0006] In some embodiments, the iNKT is CD3+Vα24Jα18+.

[0007] In some embodiments, each unit dose of therapeutic cell population comprises 1.0 x 10 cells per kilogram of body weight of the subject receiving the cell transplant. 6 ~50×10 6 0.3 x 10 HSPCs per kilogram of body weight of the subject receiving the cell graft 6 ~1000×10 6 0.5 x 10 Tmems per kilogram of body weight of the subject receiving the cell graft 6 ~1000×10 6 Tregs, and 3 x 10 per kilogram of body weight of the subject receiving the cell graft 5 Contains fewer than naive conventional αβ-T cells.

[0008] In various embodiments, the unit dose further comprises iNKT cells, and the population of therapeutic cells in each unit dose is 1.0 x 10 per kilogram of body weight of the subject receiving the cell transplant. 6 ~50×10 6 0.3 x 10 HSPCs per kilogram of body weight of the subject receiving the cell graft 6 ~1000×10 6 0.5 x 10 Tmems per kilogram of body weight of the subject receiving the cell graft 6 ~1000×10 60.5 x 10 Tregs per kilogram of body weight of the subject receiving the cell graft 3 ~2000×10 3 cells per kilogram of body weight of the subject receiving the iNKT, and 3 x 10 cells per kilogram of body weight of the subject receiving the cell graft 5 Contains fewer than naive conventional αβ-T cells.

[0009] In some embodiments, each unit dose of therapeutic cell population comprises 0.2 x 10 cells per kilogram of body weight of the subject receiving the cell transplant. 6 ~500×10 6 Contains naive Treg cells.

[0010] In some embodiments, each unit dose of therapeutic cell population comprises 0.2 x 10 cells per kilogram of body weight of the subject receiving the cell transplant. 6 ~500×10 6 Contains naive Treg cells.

[0011] In various embodiments, each unit dose of therapeutic cell population comprises 1.0 x 10 cells per kilogram of body weight of the subject receiving the cell transplant. 6 ~50×10 6 Contains HSPCs.

[0012] In some embodiments, each unit dose of therapeutic cell population comprises 1.0 x 10 cells per kilogram of body weight of the subject receiving the cell transplant. 6 ~250×10 6 Contains Tmem.

[0013] In some embodiments, each unit dose of the therapeutic cell population comprises 1 x 10 cells per kilogram of body weight of the subject receiving the cell transplant. 5 Contains fewer than naive conventional αβ-T cells.

[0014] In various embodiments, each unit dose of therapeutic cell population comprises 1 x 10 cells per kilogram of body weight of the subject receiving the cell transplant. 6 ~2.5×10 6 Contains Treg cells.

[0015] In some embodiments, the unit dose is 1 x 10 per kilogram of body weight of the subject receiving the cell transplant. 4 ~200×10 4 It further includes iNKT.

[0016] In embodiments, the pharmaceutical composition is suitable for administration to a subject receiving a cell transplant.

[0017] In various embodiments, the pharmaceutical composition further comprises an excipient. Optionally, the excipient is Normosol-R. Optionally, the excipient is human serum.

[0018] In some embodiments, the HSPCs are half-matched to the subject receiving the cell graft.

[0019] In embodiments, the Tregs, Tmems, or a combination thereof are HLA-matched to the subject receiving the cell graft.

[0020] In various embodiments, at least a portion of the population of therapeutic cells is autologous to the subject receiving the cell transplant.

[0021] In some embodiments, the subject receiving the pharmaceutical composition or cell transplant has undergone a myeloablative conditioning regimen that includes thiotepa.

[0022] In embodiments, the subject receiving the pharmaceutical composition or cell transplant is receiving a GVHD prophylaxis regimen that includes tacrolimus.

[0023] In various embodiments, the subject receiving the pharmaceutical composition or cell transplant will be receiving a GVHD prophylaxis regimen that includes tacrolimus.

[0024] Another embodiment of the present disclosure is a pharmaceutical composition comprising a population of therapeutic cells enriched for hematopoietic stem / progenitor cells (HSPCs), memory T cells (Tmems), and regulatory T cells (Tregs), wherein the population of cells is depleted of naive conventional αβ-T cells, and the population of therapeutic cells comprises a ratio of naive conventional αβ-T cells to HSPCs of less than 1:400, a ratio of naive conventional αβ-T cells to Tmems of less than 1:800, and a ratio of naive conventional αβ-T cells to Tregs of less than 1:5. In this embodiment, the subject receiving the pharmaceutical composition has undergone a myeloablative transplant conditioning regimen comprising thiotepa, and / or the subject receiving the cell graft is undergoing or will undergo a GVHD prophylaxis regimen comprising tacrolimus.

[0025] In some embodiments, the population of therapeutic cells further comprises invariant natural killer T cells (iNKT), wherein the population of therapeutic cells comprises a ratio of naive conventional αβ-T cells to iNKT of less than 100:1.

[0026] In embodiments, the ratio of naive conventional αβ-T cells to Tmem is less than 1:3.

[0027] In various embodiments, the population of therapeutic cells comprises a ratio of naive conventional αβ-T cells to naive Tregs of less than 1:2.

[0028] In some embodiments, the subject receiving the pharmaceutical composition or cell transplant has undergone a myeloablative conditioning regimen that includes thiotepa.

[0029] In embodiments, the subject receiving the pharmaceutical composition or cell transplant is receiving a GVHD prophylaxis regimen that includes tacrolimus.

[0030] In various embodiments, the subject receiving the pharmaceutical composition or cell transplant will be receiving a GVHD prophylaxis regimen that includes tacrolimus.

[0031] It will be understood that various aspects and / or embodiments of the present disclosure can be recognized individually, collectively, or in combination with each other. Any description herein of a specific composition and / or method can be applied to and used with any other specific composition and / or method disclosed herein. Furthermore, any composition disclosed herein can be applied to any method disclosed herein. In other words, any aspect or embodiment described herein can be combined with any other aspect or embodiment disclosed herein.

[0032] Certain embodiments of the present disclosure include isolated CD45 + and a cell therapy product comprising a population of isolated CD45 + The population of cells is a) approximately 1.0 x 10 per kilogram of body weight of the human subject receiving the product 5 ~Approx. 1.0×10 8 CD34 + A dose of hematopoietic stem and progenitor cells (HSPCs), or approximately 5.0 × 10 5 ~Approx. 1.5×10 10 CD34 + a total dose of hematopoietic stem and progenitor cells (HSPCs), b) approximately 1.0 × 10 per kilogram of body weight of the human subject receiving the product 5 ~Approx. 1.0×10 8 CD45RA - A dose of memory T cells (Tmem), or approximately 5.0 × 10 5 ~Approx. 1.5×10 10 CD45RA - and c) approximately 1.0 x 10 total dose of memory T cells (Tmem) per kilogram of body weight of the human subject receiving the product. 5 ~Approx. 2.0×10 7 fresh CD4 + CD25 + CD127 dim Regulatory T cell (Treg) dose, or approximately 5.0 × 10 5 ~Approx. 3.0×10 9 Pieces of isolated fresh + CD4 + CD25 + CD127 dimThe cell therapy product contains a total dose of regulatory T cells (Tregs) of approximately 5.0 x 10 per kilogram of body weight of the human subject receiving the product. 5 < naive conventional CD3 + CD25 - CD45RA + T cells (Tcon), approximately 6.0×10 7 < 100 total naive conventional CD3 + CD25 - CD45RA + T cells (Tcon), or approximately 1.0 × 10 6 < 100 total naive conventional CD3 + CD25 - CD45RA + Naive conventional CD3 to contain T cells (Tcon) + CD25 - CD45RA + T cell (Tcon) depleted and isolated CD45 + The population of cells is formulated with an excipient at a neutral pH.

[0033] In some embodiments, the dose of HSPCs is about 1.0 x 10 per kilogram of body weight of the human subject receiving the product. 5 Approximately 2.0 x 10 HSPCs per kilogram of body weight of the human subject receiving the product 5 Approximately 3.0 x 10 HSPCs per kilogram of body weight of the human subject receiving the product 5 Approximately 4.0 x 10 HSPCs per kilogram of body weight of the human subject receiving the product 5 Approximately 5.0 x 10 HSPCs per kilogram of body weight of the human subject receiving the product 5 ≥ 6.0 x 10 HSPCs per kilogram of body weight of the human subject receiving the product 5 ≥ 7.0 x 10 HSPCs per kilogram of body weight of the human subject receiving the product 5 Approximately 8.0 x 10 HSPCs per kilogram of body weight of the human subject receiving the product 5 Approximately 9.0 x 10 HSPCs per kilogram of body weight of the human subject receiving the product 5≥ 1.0 x 10 HSPCs per kilogram of body weight of the human subject receiving the product 6 Approximately 1.5 x 10 HSPCs per kilogram of body weight of the human subject receiving the product 6 Approximately 2.0 x 10 HSPCs per kilogram of body weight of the human subject receiving the product 6 ≥ 2.5 x 10 HSPCs per kilogram of body weight of the human subject receiving the product 6 Approximately 3.0 x 10 HSPCs per kilogram of body weight of the human subject receiving the product 6 Approximately 3.5 x 10 HSPCs per kilogram of body weight of the human subject receiving the product 6 Approximately 4.0 x 10 HSPCs per kilogram of body weight of the human subject receiving the product 6 Approximately 4.5 x 10 HSPCs per kilogram of body weight of the human subject receiving the product 6 Approximately 5.0 x 10 HSPCs per kilogram of body weight of the human subject receiving the product 6 5.5 x 10 HSPCs or more per kilogram of body weight of the human subject receiving the product 6 ≥ 6.0 x 10 HSPCs per kilogram of body weight of the human subject receiving the product 6 ≥ 6.5 x 10 HSPCs per kilogram of body weight of the human subject receiving the product 6 ≥ 7.0 x 10 HSPCs per kilogram of body weight of the human subject receiving the product 6 Approximately 7.5 x 10 HSPCs per kilogram of body weight of the human subject receiving the product 6 Approximately 8.0 x 10 HSPCs per kilogram of body weight of the human subject receiving the product 6 ≥ 8.5 x 10 HSPCs per kilogram of body weight of the human subject receiving the product 6 Approximately 9.0 x 10 HSPCs per kilogram of body weight of the human subject receiving the product 6 Approximately 9.5 x 10 HSPCs per kilogram of body weight of the human subject receiving the product 6 ≥ 1.0 x 10 HSPCs per kilogram of body weight of the human subject receiving the product 7Approximately 1.5 x 10 HSPCs per kilogram of body weight of the human subject receiving the product 7 Approximately 2.0 x 10 HSPCs per kilogram of body weight of the human subject receiving the product 7 ≥ 2.5 x 10 HSPCs per kilogram of body weight of the human subject receiving the product 7 Approximately 3.0 x 10 HSPCs per kilogram of body weight of the human subject receiving the product 7 Approximately 3.5 x 10 HSPCs per kilogram of body weight of the human subject receiving the product 7 Approximately 4.0 x 10 HSPCs per kilogram of body weight of the human subject receiving the product 7 Approximately 4.5 x 10 HSPCs per kilogram of body weight of the human subject receiving the product 7 Approximately 5.0 x 10 HSPCs per kilogram of body weight of the human subject receiving the product 7 5.5 x 10 HSPCs or more per kilogram of body weight of the human subject receiving the product 7 ≥ 6.0 x 10 HSPCs per kilogram of body weight of the human subject receiving the product 7 ≥ 6.5 x 10 HSPCs per kilogram of body weight of the human subject receiving the product 7 ≥ 7.0 x 10 HSPCs per kilogram of body weight of the human subject receiving the product 7 Approximately 7.5 x 10 HSPCs per kilogram of body weight of the human subject receiving the product 7 Approximately 8.0 x 10 HSPCs per kilogram of body weight of the human subject receiving the product 7 ≥ 8.5 x 10 HSPCs per kilogram of body weight of the human subject receiving the product 7 Approximately 9.0 x 10 HSPCs per kilogram of body weight of the human subject receiving the product 7 Approximately 9.5 x 10 HSPCs per kilogram of body weight of the human subject receiving the product 7 or more than about 1.0 x 10 HSPCs per kilogram of body weight of the human subject receiving the product 8 In some embodiments that may be combined with any of the preceding embodiments, the dose of HSPCs is about 5.0 x 10 or more. 5More than 6.0 x 10 HSPCs 5 More than 7.0 x 10 HSPCs 5 More than HSPCs, approximately 8.0 x 10 5 More than 9.0 x 10 HSPCs 5 More than 1.0 x 10 HSPCs 6 More than 1.5 x 10 HSPCs 6 More than HSPCs, approximately 2.0 x 10 6 More than HSPCs, approximately 2.5 x 10 6 More than 3.0 x 10 HSPCs 6 More than HSPCs, approximately 3.5 x 10 6 More than HSPCs, approximately 4.0 x 10 6 More than HSPCs, approximately 4.5 x 10 6 More than 5.0 x 10 HSPCs 6 More than 5.5 x 10 HSPCs 6 More than 6.0 x 10 HSPCs 6 More than 6.5 x 10 HSPCs 6 More than 7.0 x 10 HSPCs 6 More than 7.5 x 10 HSPCs 6 More than HSPCs, approximately 8.0 x 10 6 More than HSPCs, approximately 8.5 x 10 6 More than 9.0 x 10 HSPCs 6 More than 9.5 x 10 HSPCs 6 More than 1.0 x 10 HSPCs 7 More than 1.5 x 10 HSPCs 7 More than HSPC, approximately 2.0x10 7 More than HSPCs, approximately 2.5 x 10 7 More than 3.0 x 10 HSPCs 7 More than HSPCs, approximately 3.5 x 10 7 More than HSPCs, approximately 4.0 x 10 7 More than HSPCs, approximately 4.5 x 10 7 More than 5.0 x 10 HSPCs 7 More than 5.5 x 10 HSPCs 7 More than 6.0 x 10 HSPCs 7 More than 6.5 x 10 HSPCs 7More than 7.0 x 10 HSPCs 7 More than 7.5 x 10 HSPCs 7 More than HSPCs, approximately 8.0 x 10 7 More than HSPCs, approximately 8.5 x 10 7 More than 9.0 x 10 HSPCs 7 More than 9.5 x 10 HSPCs 7 More than 1.0 x 10 HSPCs 8 More than 1.5 x 10 HSPCs 8 More than HSPCs, approximately 2.0 x 10 8 More than HSPCs, approximately 2.5 x 10 8 More than 3.0 x 10 HSPCs 8 HSPCs, approximately 3.5 × 10 HSPCs, approximately 4.0 × 10 8 More than HSPCs, approximately 4.5 x 10 8 More than 5.0 x 10 HSPCs 8 More than 5.5 x 10 HSPCs 8 More than 6.0 x 10 HSPCs 8 More than 6.5 x 10 HSPCs 8 More than 7.0 x 10 HSPCs 8 More than 7.5 x 10 HSPCs 8 More than HSPCs, approximately 8.0 x 10 8 More than HSPCs, approximately 8.5 x 10 8 More than 9.0 x 10 HSPCs 8 More than 9.5 x 10 HSPCs 8 More than 1.0 x 10 HSPCs 9 More than 1.5 x 10 HSPCs 9 More than HSPCs, approximately 2.0 x 10 9 More than HSPCs, approximately 2.5 x 10 9 More than 3.0 x 10 HSPCs 9 More than HSPCs, approximately 3.5 x 10 9 More than HSPCs, approximately 4.0 x 10 9 More than HSPCs, approximately 4.5 x 10 9 More than 5.0 x 10 HSPCs 9 More than 5.5 x 10 HSPCs 9 More than 6.0 x 10 HSPCs 9More than 6.5 x 10 HSPCs 9 More than 7.0 x 10 HSPCs 9 More than 7.5 x 10 HSPCs 9 More than HSPCs, approximately 8.0 x 10 9 More than HSPCs, approximately 8.5 x 10 9 More than 9.0 x 10 HSPCs 9 More than 9.5 x 10 HSPCs 9 More than 1.0 x 10 HSPCs 10 or more HSPCs, or approximately 1.5 x 10 10 In some embodiments that may be combined with any of the preceding embodiments, the dose of Tmem is about 1.0 x 10 per kilogram of body weight of the human subject receiving the product. 5 ≥ 2.0 x 10 Tmems per kilogram of body weight of the human subject receiving the product 5 ≥ 3.0 x 10 Tmems per kilogram of body weight of the human subject receiving the product 5 or more Tmems, approximately 4.0 x 10 per kilogram of body weight of the human subject receiving the product 5 or more Tmems, approximately 5.0 x 10 per kilogram of body weight of the human subject receiving the product 5 ≥ 6.0 x 10 Tmems per kilogram of body weight of the human subject receiving the product 5 ≥ 7.0 x 10 Tmems per kilogram of body weight of the human subject receiving the product 5 ≥ 8.0 x 10 Tmems per kilogram of body weight of the human subject receiving the product 5 or more Tmems, approximately 9.0 x 10 per kilogram of body weight of the human subject receiving the product 5 or more Tmems, approximately 1.0 x 10 per kilogram of body weight of the human subject receiving the product 6 ≥ 1.5 x 10 Tmems per kilogram of body weight of the human subject receiving the product 6 ≥ 2.0 x 10 Tmems per kilogram of body weight of the human subject receiving the product 6 ≥ 2.5 x 10 Tmems per kilogram of body weight of the human subject receiving the product 6≥ 3.0 x 10 Tmems per kilogram of body weight of the human subject receiving the product 6 ≥ 3.5 x 10 Tmems per kilogram of body weight of the human subject receiving the product 6 or more Tmems, approximately 4.0 x 10 per kilogram of body weight of the human subject receiving the product 6 or more Tmems, approximately 4.5 x 10 per kilogram of body weight of the human subject receiving the product 6 or more Tmems, approximately 5.0 x 10 per kilogram of body weight of the human subject receiving the product 6 or more Tmems, approximately 5.5 x 10 per kilogram of body weight of the human subject receiving the product 6 ≥ 6.0 x 10 Tmems per kilogram of body weight of the human subject receiving the product 6 or more Tmems, approximately 6.5 x 10 per kilogram of body weight of the human subject receiving the product 6 ≥ 7.0 x 10 Tmems per kilogram of body weight of the human subject receiving the product 6 ≥ 7.5 x 10 Tmems per kilogram of body weight of the human subject receiving the product 6 ≥ 8.0 x 10 Tmems per kilogram of body weight of the human subject receiving the product 6 ≥ 8.5 x 10 Tmems per kilogram of body weight of the human subject receiving the product 6 or more Tmems, approximately 9.0 x 10 per kilogram of body weight of the human subject receiving the product 6 or more Tmems per kilogram of body weight of the human subject receiving the product Approximately 9.5×10 6 or more Tmems, approximately 1.0 x 10 per kilogram of body weight of the human subject receiving the product 7 ≥ 1.5 x 10 Tmems per kilogram of body weight of the human subject receiving the product 7 ≥ 2.0 x 10 Tmems per kilogram of body weight of the human subject receiving the product 7 ≥ 2.5 x 10 Tmems per kilogram of body weight of the human subject receiving the product 7 ≥ 3.0 x 10 Tmems per kilogram of body weight of the human subject receiving the product 7≥ 3.5 x 10 Tmems per kilogram of body weight of the human subject receiving the product 7 or more Tmems, approximately 4.0 x 10 per kilogram of body weight of the human subject receiving the product 7 or more Tmems, approximately 4.5 x 10 per kilogram of body weight of the human subject receiving the product 7 or more Tmems, approximately 5.0 x 10 per kilogram of body weight of the human subject receiving the product 7 or more Tmems, approximately 5.5 x 10 per kilogram of body weight of the human subject receiving the product 7 ≥ 6.0 x 10 Tmems per kilogram of body weight of the human subject receiving the product 7 or more Tmems, approximately 6.5 x 10 per kilogram of body weight of the human subject receiving the product 7 ≥ 7.0 x 10 Tmems per kilogram of body weight of the human subject receiving the product 7 ≥ 7.5 x 10 Tmems per kilogram of body weight of the human subject receiving the product 7 ≥ 8.0 x 10 Tmems per kilogram of body weight of the human subject receiving the product 7 ≥ 8.5 x 10 Tmems per kilogram of body weight of the human subject receiving the product 7 or more Tmems, approximately 9.0 x 10 per kilogram of body weight of the human subject receiving the product 7 or more Tmems, approximately 9.5 x 10 per kilogram of body weight of the human subject receiving the product 7 or more than 1.0 x 10 per kilogram of body weight of the human subject receiving the product 8 In some embodiments that may be combined with any of the preceding embodiments, the dose of Tmem is about 5.0 x 10 or more. 5 More than 6.0 × 10 Tmem 5 More than 7.0 × 10 Tmem 5 More than 8.0 × 10 Tmem 5 More than 9.0×10 Tmem 5 More than 1.0×10 Tmem 6 More than 1.5×10 Tmem 6 More than 10 Tmem, approximately 2.0 x 10 6More than 10 Tmem, approximately 2.5 x 10 6 More than 3.0 × 10 Tmem 6 More than 3.5 × 10 Tmem 6 More than 4.0 × 10 Tmem 6 More than 4.5 × 10 Tmem 6 More than 5.0 × 10 Tmem 6 More than 5.5×10 Tmem 6 More than 6.0 × 10 Tmem 6 More than 6.5×10 Tmem 6 More than 7.0 × 10 Tmem 6 More than 7.5×10 Tmem 6 More than 8.0 × 10 Tmem 6 More than 8.5×10 Tmem 6 More than 9.0×10 Tmem 6 More than 9.5×10 Tmem 6 More than 1.0×10 Tmem 7 More than 1.5×10 Tmem 7 More than 10 Tmem, approximately 2.0 x 10 7 More than 10 Tmem, approximately 2.5 x 10 7 More than 3.0 × 10 Tmem 7 More than 3.5 × 10 Tmem 7 More than 4.0 × 10 Tmem 7 More than 4.5 × 10 Tmem 7 More than 5.0 × 10 Tmem 7 More than 5.5×10 Tmem 7 More than 6.0 × 10 Tmem 7 More than 6.5×10 Tmem 7 More than 7.0 × 10 Tmem 7 More than 7.5×10 Tmem 7 More than 8.0 × 10 Tmem 7 More than 8.5×10 Tmem 7 More than 9.0×10 Tmem 7 More than 9.5×10 Tmem 7 More than 1.0×10 Tmem 8More than 1.5×10 Tmem 8 More than 10 Tmem, approximately 2.0 x 10 8 More than 10 Tmem, approximately 2.5 x 10 8 More than 3.0 × 10 Tmem 8 More than 3.5 × 10 Tmem 8 More than 4.0 × 10 Tmem 8 More than 4.5 × 10 Tmem 8 More than 5.0 × 10 Tmem 8 More than 5.5×10 Tmem 8 More than 6.0 × 10 Tmem 8 More than 6.5×10 Tmem 8 More than 7.0 × 10 Tmem 8 More than 7.5×10 Tmem 8 More than 8.0 × 10 Tmem 8 More than 8.5×10 Tmem 8 More than 9.0×10 Tmem 8 More than 9.5×10 Tmem 8 More than 1.0×10 Tmem 9 More than 1.5×10 Tmem 9 More than 10 Tmem, approximately 2.0 x 10 9 More than 10 Tmem, approximately 2.5 x 10 9 More than 3.0 × 10 Tmem 9 More than 3.5 × 10 Tmem 9 More than 4.0 × 10 Tmem 9 More than 4.5 × 10 Tmem 9 More than 5.0 × 10 Tmem 9 More than 5.5×10 Tmem 9 More than 6.0 × 10 Tmem 9 More than 6.5×10 Tmem 9 More than 7.0 × 10 Tmem 9 More than 7.5×10 Tmem 9 More than 8.0 × 10 Tmem 9 More than 8.5×10 Tmem 9 More than 9.0×10 Tmem 9More than 9.5×10 Tmem 9 More than 1.0×10 Tmem 10 10 or more Tmem, or approximately 1.5 x 10 10 In some embodiments that may be combined with any of the preceding embodiments, the dose of fresh Tregs is about 1.0 x 10 per kilogram of body weight of the human subject receiving the product. 5 Approximately 2.0 x 10 fresh Tregs per kilogram of body weight of the human subject receiving the product 5 Approximately 3.0 x 10 fresh Tregs per kilogram of body weight of the human subject receiving the product 5 Approximately 4.0 x 10 fresh Tregs per kilogram of body weight of the human subject receiving the product 5 Approximately 5.0 x 10 fresh Tregs per kilogram of body weight of the human subject receiving the product 5 Approximately 6.0 x 10 fresh Tregs per kilogram of body weight of the human subject receiving the product 5 Approximately 7.0 x 10 fresh Tregs per kilogram of body weight of a human subject receiving the product 5 Approximately 8.0 x 10 fresh Tregs per kilogram of body weight of a human subject receiving the product 5 Approximately 9.0 x 10 fresh Tregs per kilogram of body weight of a human subject receiving the product 5 fresh Tregs, approximately 1.0 x 10 per kilogram of body weight of the human subject receiving the product 6 fresh Tregs, approximately 1.5 x 10 per kilogram of body weight of the human subject receiving the product 6 Approximately 2.0 x 10 fresh Tregs per kilogram of body weight of the human subject receiving the product 6 fresh Tregs, approximately 2.5 x 10 per kilogram of body weight of the human subject receiving the product 6 Approximately 3.0 x 10 fresh Tregs per kilogram of body weight of the human subject receiving the product 6 fresh Tregs, approximately 3.5 x 10 per kilogram of body weight of the human subject receiving the product 6 Approximately 4.0 x 10 fresh Tregs per kilogram of body weight of the human subject receiving the product 6fresh Tregs, approximately 4.5 x 10 per kilogram of body weight of the human subject receiving the product 6 Approximately 5.0 x 10 fresh Tregs per kilogram of body weight of the human subject receiving the product 6 Approximately 5.5 x 10 fresh Tregs per kilogram of body weight of a human subject receiving the product 6 Approximately 6.0 x 10 fresh Tregs per kilogram of body weight of the human subject receiving the product 6 Approximately 6.5 x 10 fresh Tregs per kilogram of body weight of the human subject receiving the product 6 Approximately 7.0 x 10 fresh Tregs per kilogram of body weight of a human subject receiving the product 6 fresh Tregs, approximately 7.5 x 10 per kilogram of body weight of the human subject receiving the product 6 Approximately 8.0 x 10 fresh Tregs per kilogram of body weight of a human subject receiving the product 6 Approximately 8.5 x 10 fresh Tregs per kilogram of body weight of the human subject receiving the product 6 Approximately 9.0 x 10 fresh Tregs per kilogram of body weight of a human subject receiving the product 6 Approximately 9.5 x 10 fresh Tregs per kilogram of body weight of the human subject receiving the product 6 fresh Tregs, approximately 1.0 x 10 per kilogram of body weight of the human subject receiving the product 7 fresh Tregs, approximately 1.5 x 10 per kilogram of body weight of the human subject receiving the product 7 or more than 2.0 x 10 fresh Tregs per kilogram of body weight of the human subject receiving the product 7 In some embodiments that may be combined with any of the preceding embodiments, the dose of fresh Tregs is about 5.0 x 10 or more. 5 More than 6.0 x 10 fresh Tregs 5 More than 7.0 x 10 fresh Tregs 5 More than 8.0 x 10 fresh Tregs 5 More than 9.0 x 10 fresh Tregs 5 More than 1.0 x 10 fresh Tregs 6More than 1.5 x 10 fresh Tregs 6 More than 2.0 x 10 fresh Tregs 6 More than 2.5 x 10 fresh Tregs 6 More than 3.0 x 10 fresh Tregs 6 More than 3.5 x 10 fresh Tregs 6 More than 4.0 x 10 fresh Tregs 6 More than 4.5 x 10 fresh Tregs 6 More than 5.0 x 10 fresh Tregs 6 More than 5.5 x 10 fresh Tregs 6 More than 6.0 x 10 fresh Tregs 6 More than 6.5 x 10 fresh Tregs 6 More than 7.0 x 10 fresh Tregs 6 More than 7.5 x 10 fresh Tregs 6 More than 8.0 x 10 fresh Tregs 6 More than 8.5 x 10 fresh Tregs 6 More than 9.0 x 10 fresh Tregs 6 More than 9.5 x 10 fresh Tregs 6 More than 1.0 x 10 fresh Tregs 7 More than 1.5 x 10 fresh Tregs 7 More than 2.0 x 10 fresh Tregs 7 More than 2.5 x 10 fresh Tregs 7 More than 3.0 x 10 fresh Tregs 7 More than 3.5 x 10 fresh Tregs 7 More than 4.0 x 10 fresh Tregs 7 More than 4.5 x 10 fresh Tregs 7 More than 5.0 x 10 fresh Tregs 7 More than 5.5 x 10 fresh Tregs 7 More than 6.0 x 10 fresh Tregs 7 More than 6.5 x 10 fresh Tregs 7 More than 100 fresh trees g, approx. 7.0×10 7 More than 7.5 x 10 fresh Tregs7 More than 8.0 x 10 fresh Tregs 7 More than 8.5 x 10 fresh Tregs 7 More than 9.0 x 10 fresh Tregs 7 More than 9.5 x 10 fresh Tregs 7 More than 1.0 x 10 fresh Tregs 8 More than 1.5 x 10 fresh Tregs 8 More than 2.0 x 10 fresh Tregs 8 More than 2.5 x 10 fresh Tregs 8 More than 3.0 x 10 fresh Tregs 8 More than 3.5 x 10 fresh Tregs 8 More than 4.0 x 10 fresh Tregs 8 More than 4.5 x 10 fresh Tregs 8 More than 5.0 x 10 fresh Tregs 8 More than 5.5 x 10 fresh Tregs 8 More than 6.0 x 10 fresh Tregs 8 More than 6.5 x 10 fresh Tregs 8 More than 7.0 x 10 fresh Tregs 8 More than 7.5 x 10 fresh Tregs 8 More than 8.0 x 10 fresh Tregs 8 More than 8.5 x 10 fresh Tregs 8 More than 9.0 x 10 fresh Tregs 8 More than 9.5 x 10 fresh Tregs 8 More than 1.0 x 10 fresh Tregs 9 More than 1.5 x 10 fresh Tregs 9 More than 2.0 x 10 fresh Tregs 9 More than 2.5 x 10 fresh Tregs 9 10 or more fresh Tregs, or approximately 3.0 x 10 9 In some embodiments that may be combined with any of the preceding embodiments, the cell therapy product comprises a total dose of about 5.0 x 10 fresh Tregs per kilogram of body weight of the human subject receiving the product. 5Less than approximately 4.5 x 10 per kilogram of body weight of the human subject receiving the product 5 Less than approximately 4.0 x 10 per kilogram of body weight of the human subject receiving the product 5 Less than approximately 3.5 x 10 per kilogram of body weight of the human subject receiving the product 5 Less than approximately 3.0 x 10 per kilogram of body weight of the human subject receiving the product 5 Less than approximately 2.5 x 10 per kilogram of body weight of the human subject receiving the product 5 Less than approximately 2.0 x 10 per kilogram of body weight of the human subject receiving the product 5 Less than approximately 1.5 x 10 per kilogram of body weight of the human subject receiving the product 5 Less than approximately 1.0 x 10 per kilogram of body weight of the human subject receiving the product 5 Less than approximately 9.5 x 10 per kilogram of body weight of the human subject receiving the product 4 Less than approximately 9.0 x 10 per kilogram of body weight of the human subject receiving the product 4 Less than approximately 8.5 x 10 per kilogram of body weight of the human subject receiving the product 4 Less than approximately 8.0 x 10 per kilogram of body weight of the human subject receiving the product 4 Less than approximately 7.5 x 10 per kilogram of body weight of the human subject receiving the product 4 Less than approximately 7.0 x 10 per kilogram of body weight of the human subject receiving the product 4 Less than approximately 6.5 x 10 per kilogram of body weight of the human subject receiving the product 4 Less than approximately 6.0 x 10 per kilogram of body weight of the human subject receiving the product 4 Less than approximately 5.5 x 10 per kilogram of body weight of the human subject receiving the product 4 Less than approximately 5.0 x 10 per kilogram of body weight of the human subject receiving the product 4 Less than approximately 4.5 x 10 per kilogram of body weight of the human subject receiving the product 4Less than approximately 4.0 x 10 per kilogram of body weight of the human subject receiving the product 4 Less than approximately 3.5 x 10 per kilogram of body weight of the human subject receiving the product 4 Less than approximately 3.0 x 10 per kilogram of body weight of the human subject receiving the product 4 Less than approximately 2.5 x 10 per kilogram of body weight of the human subject receiving the product 4 Less than approximately 2.0 x 10 per kilogram of body weight of the human subject receiving the product 4 Less than approximately 1.5 x 10 per kilogram of body weight of the human subject receiving the product 4 Less than approximately 1.0 x 10 per kilogram of body weight of the human subject receiving the product 4 Less than approximately 9.5 x 10 per kilogram of body weight of the human subject receiving the product 3 Less than approximately 9.0 x 10 per kilogram of body weight of the human subject receiving the product 3 Less than approximately 8.5 x 10 per kilogram of body weight of the human subject receiving the product 3 Less than approximately 8.0 x 10 per kilogram of body weight of the human subject receiving the product 3 Less than approximately 7.5 x 10 per kilogram of body weight of the human subject receiving the product 3 Less than approximately 7.0 x 10 per kilogram of body weight of the human subject receiving the product 3 Less than approximately 6.5 x 10 per kilogram of body weight of the human subject receiving the product 3 Less than approximately 6.0 x 10 per kilogram of body weight of the human subject receiving the product 3 Less than approximately 5.5 x 10 per kilogram of body weight of the human subject receiving the product 3 Less than approximately 5.0 x 10 per kilogram of body weight of the human subject receiving the product 3 Less than approximately 4.5 x 10 per kilogram of body weight of the human subject receiving the product 3 Less than approximately 4.0 x 10 per kilogram of body weight of the human subject receiving the product 3Less than approximately 3.5 x 10 per kilogram of body weight of the human subject receiving the product 3 Less than approximately 3.0 x 10 per kilogram of body weight of the human subject receiving the product 3 Less than approximately 2.5 x 10 per kilogram of body weight of the human subject receiving the product 3 Less than approximately 2.0 x 10 per kilogram of body weight of the human subject receiving the product 3 Less than approximately 1.5 x 10 per kilogram of body weight of the human subject receiving the product 3 Less than 1.0 x 10 per kilogram of body weight of the human subject receiving the product 3 In some embodiments that may be combined with any of the preceding embodiments, the cell therapy product contains less than about 6.0 x 10 Tcon. 7 Total Tcon of less than 5.5 x 10 7 Total Tcon less than 5.0 x 10 7 Total Tcon of less than 4.5 x 10 7 Total Tcon less than 4.0 x 10 7 Total Tcon of less than 3.5 x 10 7 Total Tcon less than 3.0 x 10 7 Total Tcon of less than 2.5 x 10 7 Total Tcon less than 2.0 x 10 7 Total Tcon of less than 1.5 x 10 7 Total Tcon less than 1.0 x 10 7 Total Tcon of less than 9.5 x 10 6 Total Tcon less than 9.0 x 10 6 Total Tcon of less than 8.5 x 10 6 Total Tcon of less than 8.0 x 10 6 Total Tcon of less than 7.5 x 10 6 Total Tcon less than 7.0 x 10 6 Total Tcon of less than 6.5 x 10 6 Total Tcon less than 6.0 x 10 6 Total Tcon of less than 5.5 x 10 6 Total Tcon less than 5.0 x 10 6 Total Tcon of less than 4.5 x 106 Total Tcon less than 4.0 x 10 6 Total Tcon of less than 3.5 x 10 6 Total Tcon less than 3.0 x 10 6 Total Tcon of less than 2.5 x 10 6 Total Tcon less than 2.0 x 10 6 Total Tcon of less than 1.5 x 10 6 Less than 1.0 x 10 total Tcon 6 In some embodiments that may be combined with any of the preceding embodiments, the isolated CD45 + The population of cells is formulated in a volume ranging from about 5 mL to about 1 L. In some embodiments that may be combined with any of the preceding embodiments, the isolated CD45 +The population of cells may be about 5 mL, about 10 mL, about 15 mL, about 20 mL, about 25 mL, about 30 mL, about 35 mL, about 40 mL, about 45 mL, about 50 mL, about 55 mL, about 60 mL, about 65 mL, about 70 mL, about 75 mL, about 80 mL, about 85 mL, about 90 mL, about 95 mL, about 100 mL, about 125 mL, about 150 mL, about 175 mL, about 200 mL, about 225 mL, about 250 mL, about 275 mL, about 300 mL, about 325 mL, about 350 mL, about 400 mL, about 450 mL, about 500 mL, about 550 mL, about 600 mL, about 650 mL, about 700 mL, about 750 mL, about 800 mL, about 850 mL, about 900 mL, about 950 mL, about 1000 mL, about 1250 mL, about 1500 mL, about 175 mL, about 2000 mL, about 2250 mL, about 250 mL, about 275 mL, about 3000 mL, about 3250 mL, about 3500 mL, about 4500 mL, about 4600 mL, about 4750 mL, about 4800 mL, about 4850 mL, about 4900 mL, about 5000 mL, about 5100 mL, about 5200 mL, about 5300 mL, about 5400 mL, about 5500 mL, about 5600 mL, about 5700 mL, about 5800 mL, about 5900 mL, about 6000 mL, about 6100 mL, about The formulation is formulated in a volume of about 375 mL, about 400 mL, about 425 mL, about 450 mL, about 475 mL, about 500 mL, about 525 mL, about 550 mL, about 575 mL, about 600 mL, about 625 mL, about 650 mL, about 675 mL, about 700 mL, about 725 mL, about 750 mL, about 775 mL, about 800 mL, about 825 mL, about 850 mL, about 875 mL, about 900 mL, about 925 mL, about 950 mL, about 975 mL, or about 1 L. In some embodiments that may be combined with any of the preceding embodiments, the neutral pH is in the range of about 6.8 to 7.6. In some embodiments that may be combined with any of the preceding embodiments, the excipient comprises a transport buffer. In some embodiments that may be combined with any of the preceding embodiments, the transport buffer comprises about 120 to about 160 mEq sodium. In some embodiments that may be combined with any of the preceding embodiments, the transport buffer comprises a total of about 270 to about 320 mOsmol / L. In some embodiments that may be combined with any of the preceding embodiments, the transport buffer is selected from phosphate buffered saline (PBS), human serum, PlasmaLyte, Normosol-R, and any combination thereof. In some embodiments that may be combined with any of the preceding embodiments, the transport buffer further comprises about 0.1% v / v to about 10% v / v of a human carrier protein. In some embodiments that may be combined with any of the preceding embodiments, the human carrier protein is selected from human serum albumin (HSA), intravenous immunoglobulin (IVIG), AB serum, and any combination thereof. In some embodiments that may be combined with any of the preceding embodiments, the isolated CD45 +The population of cells is formulated in a single-dose transfer bag. In some embodiments that may be combined with any of the preceding embodiments, the single-dose transfer bag is a polyvinyl chloride (PVC) transfer bag or an ethylene vinyl acetate (EVA) transfer bag. In some embodiments that may be combined with any of the preceding embodiments, the isolated CD45 + The population of cells is enriched for HSPCs, Tmems, and Tregs. In some embodiments that may be combined with any of the preceding embodiments, the isolated CD45 + The cell population should be less than 1:3, less than 1:5, less than 1:10, less than 1:20, less than 1:30, less than 1:40, less than 1:50, less than 1:60, less than 1:70, less than 1:80, less than 1:90, less than 1:100, less than 1:200, less than 1:300, less than 1:400, less than 1:500, less than 1:600, less than 1:700, less than 1:800, less than 1:900, less than 1:1,000, less than 1:1,500, less than 1:2,000, less than 1:2,500, less than 1:3,000, less than 1:3,500, less than 1:4,000, less than 1:4,500, less than 1:5,000, less than 1:5,500, less than 1:6,000, less than 1:6, Less than 500, Less than 1:7,000, Less than 1:7,500, Less than 1:8,000, Less than 1:8,500, Less than 1:9,000, Less than 1:9,500, Less than 1:10,000, Less than 1:15,000, Less than 1:20,000, Less than 1:25,000, Less than 1:30,000, Less than 1:35,000, Less than 1:40,000, Less than 1:45,000, Less than 1:50,000, Less than 1:55,000, Less than 1:60,000, Less than 1:65,000, Less than 1:70 In some embodiments that may be combined with any of the preceding embodiments, the isolated CD45 Tcon to HSPC ratio may be less than 1:1,000, less than 1:75,000, less than 1:80,000, less than 1:85,000, less than 1:90,000, less than 1:95,000, less than 1:100,000, less than 1:200,000, less than 1:300,000, less than 1:400,000, less than 1:500,000, less than 1:600,000, less than 1:700,000, less than 1:800,000, less than 1:900,000, or less than 1:1,000,000.+ The cell populations are <1:10, <1:20, <1:30, <1:40, <1:50, <1:60, <1:70, <1:80, <1:90, <1:100, <1:200, <1:300, <1:400, <1:500, <1:600, <1:700, <1:800, <1:900, <1:1,000, <1:1,500, <1:2,000, <1:2,500, <1:3,000, <1:3,500, <1:4,000, <1:4,500 In some embodiments that may be combined with any of the preceding embodiments, the isolated CD45 comprises a Tcon to Tmem ratio of less than 1:5,000, less than 1:5,500, less than 1:6,000, less than 1:6,500, less than 1:7,000, less than 1:7,500, less than 1:8,000, less than 1:8,500, less than 1:9,000, less than 1:9,500, less than 1:10,000, less than 1:15,000, less than 1:20,000, less than 1:25,000, less than 1:30,000, less than 1:35,000, less than 1:40,000, less than 1:45,000, or less than 1:50,000. +The cell populations are less than 1:1, less than 1:2, less than 1:3, less than 1:4, less than 1:5, less than 1:6, less than 1:7, less than 1:8, less than 1:9, less than 1:10, less than 1:11, less than 1:12, less than 1:13, less than 1:14, less than 1:15, less than 1:16, less than 1:17, less than 1:18, less than 1:19, less than 1:20, less than 1:30, less than 1:40, less than 1:50, less than 1:60, less than 1:70, less than 1:80, less than 1:90, less than 1:100, less than 1:200, less than 1:300, less than 1:400, less than 1:500, less than 1:600, less than 1:700, less than 1:800, less than 1:900, less than 1:1,000, and less than 1:1,500. , including a Tcon to Treg ratio of less than 1:2,000, less than 1:2,500, less than 1:3,000, less than 1:3,500, less than 1:4,000, less than 1:4,500, less than 1:5,000, less than 1:5,500, less than 1:6,000, less than 1:6,500, less than 1:7,000, less than 1:7,500, less than 1:8,000, less than 1:8,500, less than 1:9,000, less than 1:9,500, less than 1:10,000, less than 1:15,000, less than 1:20,000, less than 1:25,000, less than 1:30,000, less than 1:35,000, less than 1:40,000, less than 1:45,000, or less than 1:50,000. In some embodiments that may be combined with any of the preceding embodiments, isolated CD45 + The population of cells comprises a ratio of HSPCs to Tmems of about 500:1 to about 1:1,000. In some embodiments that may be combined with any of the preceding embodiments, the isolated CD45 + The population of cells comprises a ratio of HSPCs to Tregs of about 100:1 to about 1:30. In some embodiments that may be combined with any of the preceding embodiments, the isolated CD45 + The population of cells comprises a ratio of Tmem to Treg of about 2000:1 to about 1:10. In some embodiments that may be combined with any of the preceding embodiments, the isolated CD45 + A population of cells expressing TCR Vα24Jα18 + CD127 +In some embodiments that may be combined with any of the preceding embodiments, the isolated CD45 + The population of cells is approximately 5.0 x 10 per kilogram of body weight of the human subject receiving the product. 2 ~Approx. 2.0×10 6 dose of iNKT, or approximately 2.0 x 10 3 ~Approx. 4.0×10 8 In some embodiments that may be combined with any of the preceding embodiments, the dose of iNKT is about 5.0 x 10 per kilogram of body weight of the human subject receiving the product. 2 6.0 x 10 iNKTs or more per kilogram of body weight of the human subject receiving the product 2 7.0 x 10 iNKTs or more per kilogram of body weight of the human subject receiving the product 2 8.0 x 10 iNKTs or more per kilogram of body weight of the human subject receiving the product 2 or more iNKT, approximately 9.0 x 10 per kilogram of body weight of the human subject receiving the product 2 or more iNKT, approximately 1.0 x 10 per kilogram of body weight of the human subject receiving the product 3 or more iNKT, approximately 2.0 x 10 per kilogram of body weight of the human subject receiving the product 3 or more iNKT, approximately 3.0 x 10 per kilogram of body weight of the human subject receiving the product 3 4.0 x 10 iNKTs or more per kilogram of body weight of the human subject receiving the product 3 or more iNKT, approximately 5.0 x 10 per kilogram of body weight of the human subject receiving the product 3 6.0 x 10 iNKTs or more per kilogram of body weight of the human subject receiving the product 3 7.0 x 10 iNKTs or more per kilogram of body weight of the human subject receiving the product 3 8.0 x 10 iNKTs or more per kilogram of body weight of the human subject receiving the product 3 or more iNKT, approximately 9.0 x 10 per kilogram of body weight of the human subject receiving the product 3or more iNKT, approximately 1.0 x 10 per kilogram of body weight of the human subject receiving the product 4 or more iNKT, approximately 2.0 x 10 per kilogram of body weight of the human subject receiving the product 4 or more iNKT, approximately 3.0 x 10 per kilogram of body weight of the human subject receiving the product 4 4.0 x 10 iNKTs or more per kilogram of body weight of the human subject receiving the product 4 or more iNKT, approximately 5.0 x 10 per kilogram of body weight of the human subject receiving the product 4 6.0 x 10 iNKTs or more per kilogram of body weight of the human subject receiving the product 4 7.0 x 10 iNKTs or more per kilogram of body weight of the human subject receiving the product 4 8.0 x 10 iNKTs or more per kilogram of body weight of the human subject receiving the product 4 or more iNKT, approximately 9.0 x 10 per kilogram of body weight of the human subject receiving the product 4 or more iNKT, approximately 1.0 x 10 per kilogram of body weight of the human subject receiving the product 5 or more iNKT, approximately 2.0 x 10 per kilogram of body weight of the human subject receiving the product 5 or more iNKT, approximately 3.0 x 10 per kilogram of body weight of the human subject receiving the product 5 4.0 x 10 iNKTs or more per kilogram of body weight of the human subject receiving the product 5 or more iNKT, approximately 5.0 x 10 per kilogram of body weight of the human subject receiving the product 5 6.0 x 10 iNKTs or more per kilogram of body weight of the human subject receiving the product 5 7.0 x 10 iNKTs or more per kilogram of body weight of the human subject receiving the product 5 8.0 x 10 iNKTs or more per kilogram of body weight of the human subject receiving the product 5 or more iNKT, approximately 9.0 x 10 per kilogram of body weight of the human subject receiving the product 5 or more iNKT, approximately 1.0 x 10 per kilogram of body weight of the human subject receiving the product 6or more iNKT, approximately 1.5 x 10 per kilogram of body weight of the human subject receiving the product 6 or more than 2.0 x 10 iNKTs per kilogram of body weight of a human subject receiving the product 6 In some embodiments that may be combined with any of the preceding embodiments, the dose of iNKT is about 2.0 x 10 or more. 3 More than 3.0 x 10 iNKT 3 More than 4.0 x 10 iNKT 3 More than 5.0 x 10 iNKT 3 More than 6.0 x 10 iNKT 3 More than 7.0 x 10 iNKT 3 More than 8.0 x 10 iNKT 3 More than 9.0 x 10 iNKT 3 More than 1.0 x 10 iNKT 4 More than 2.0 x 10 iNKT 4 More than 3.0 x 10 iNKT 4 More than 4.0 x 10 iNKT 4 More than 5.0 x 10 iNKT 4 More than 6.0 x 10 iNKT 4 More than 7.0 x 10 iNKT 4 More than 8.0 x 10 iNKT 4 More than 9.0 x 10 iNKT 4 More than 1.0 x 10 iNKT 5 More than 2.0 x 10 iNKT 5 More than 3.0 x 10 iNKT 5 More than 4.0 x 10 iNKT 5 More than 5.0 x 10 iNKT 5 More than 6.0 x 10 iNKT 5 More than 7.0 x 10 iNKT 5 More than 8.0 x 10 iNKT 5 More than 9.0 x 10 iNKT 5 More than 1.0 x 10 iNKT 6 More than 1.5 x 10 iNKT 6 More than 2.0 x 10 iNKT 6More than 2.5 x 10 iNKT 6 More than 3.0 x 10 iNKT 6 More than 3.5 x 10 iNKT 6 More than 4.0 x 10 iNKT 6 More than 4.5 x 10 iNKT 6 More than 5.0 x 10 iNKT 6 More than 5.5 x 10 iNKT 6 More than 6.0 x 10 iNKT 6 More than 6.5 x 10 iNKT 6 More than 7.0 x 10 iNKT 6 More than 7.5 x 10 iNKT 6 More than 8.0 x 10 iNKT 6 More than 8.5 x 10 iNKT 6 More than 9.0 x 10 iNKT 6 More than 9.5 x 10 iNKT 6 More than 1.0 x 10 iNKT 7 More than 1.5 x 10 iNKT 7 More than 2.0 x 10 iNKT 7 More than 2.5 x 10 iNKT 7 More than 3.0 x 10 iNKT 7 More than 3.5 x 10 iNKT 7 More than 4.0 x 10 iNKT 7 More than 4.5 x 10 iNKT 7 More than 5.0 x 10 iNKT 7 More than 5.5 x 10 iNKT 7 More than 6.0 x 10 iNKT 7 More than 6.5 x 10 iNKT 7 More than 7.0 x 10 iNKT 7 More than 7.5 x 10 iNKT 7 More than 8.0 x 10 iNKT 7 More than 8.5 x 10 iNKT 7 More than 9.0 x 10 iNKT 7 More than 9.5 x 10 iNKT 7 More than 1.0 x 10 iNKT 8More than 1.5 x 10 iNKT 8 More than 2.0 iNKT x10 8 More than 2.5 x 10 iNKT 8 More than 3.0 x 10 iNKT 8 More than 3.5 x 10 iNKT 8 10 or more iNKTs, or approximately 4.0 x 10 8 In some embodiments that may be combined with any of the preceding embodiments, the total dose of iNKT comprises an isolated CD45 + The population of cells comprises a ratio of HSPC to iNKT of about 1:2 to about 500,000:1. In some embodiments that may be combined with any of the preceding embodiments, the isolated CD45 + The population of cells comprises an iNKT to Tcon ratio of less than 1:1, less than 1:2, less than 1:3, less than 1:4, less than 1:5, less than 1:6, less than 1:7, less than 1:8, less than 1:9, less than 1:10, less than 1:20, less than 1:30, less than 1:40, less than 1:50, less than 1:60, less than 1:70, less than 1:80, less than 1:90, or less than 1:100. In some embodiments that may be combined with any of the preceding embodiments, the isolated CD45 + The population of cells comprises an iNKT to Tmem ratio of about 5:1 to about 1:1,000,000. + , CD133 + , CD90 + , CD38 - , CD45RA - , Lin - , CD19 - , TCRα - In some embodiments that may be combined with any of the preceding embodiments, Tmem is CD3 + CD45RO + In some embodiments that may be combined with any of the preceding embodiments, Tmem is a T central memory cell (T CM ) population, T effector memory cells (T EM ) population, T stem center memory cells (T SCM), or any combination thereof. In some embodiments that may be combined with any of the preceding embodiments, T CM is CD4 + CD45RO + or CD8 + CD45RO + In some embodiments that may be combined with any of the preceding embodiments, T CM is CD45RA - , CD62L + , CCR7 + In some embodiments that may be combined with any of the preceding embodiments, T EM is CD4 + , CD45RO + , CD45RA - , CD62L - , CCR7 - In some embodiments that may be combined with any of the preceding embodiments, T SCM is CD4 + CD45RA + or CD8 + CD45RA + In some embodiments that may be combined with any of the preceding embodiments, T SCM CD95 + , CD122 + , CXCR3 + , LFA-1 + In some embodiments that may be combined with any of the preceding embodiments, Tregs are FoxP3 + In some embodiments that may be combined with any of the preceding embodiments, the Tregs comprise a population of naive Treg cells, a population of memory Treg cells, or a population of naive and memory Treg cells. In some embodiments that may be combined with any of the preceding embodiments, the naive Treg cells comprise CD4 + CD25 + CD127 dim FoxP3 + CD45RA + CD45RO- In some embodiments that may be combined with any of the preceding embodiments, the dose of Tregs is about 2.0 x 10 per kilogram of body weight of the human subject receiving the product. 5 ~Approx. 5.0×10 8 a dose of naive Treg cells, or approximately 8.0 x 10 5 ~Approx. 1.0×10 11 In some embodiments that may be combined with any of the preceding embodiments, the total dose of isolated CD45 naive Treg cells is + The population of cells comprises a ratio of HSPCs to naive Tregs of about 1:500 to about 100:1. In some embodiments that may be combined with any of the preceding embodiments, the isolated CD45 + The population of cells comprises a ratio of Tmem to naive Treg of about 3:1 to about 1:10. In some embodiments that may be combined with any of the preceding embodiments, the isolated CD45 + The population of cells comprises a ratio of Tcon to naive Treg of less than 1:1, less than 1:2, less than 1:3, less than 1:4, less than 1:5, less than 1:6, less than 1:7, less than 1:8, less than 1:9, or less than 1:10. In some embodiments that may be combined with any of the preceding embodiments, the memory Treg cells are CD4 + CD25 + CD127 dim FoxP3 + CD45RA - CD45RO + In some embodiments that may be combined with any of the preceding embodiments, the dose of Tregs is about 5.0 x 10 per kilogram of body weight of the human subject receiving the product. 4 ~Approx. 5.0×10 8 a dose of memory Treg cells, or approximately 2.0 x 10 5 ~Approx. 1.0×10 11 In some embodiments that may be combined with any of the preceding embodiments, the total dose of isolated CD45 memory Treg cells is +The population of cells comprises a ratio of HSPCs to memory Tregs of about 1:500 to about 10,000:1. In some embodiments that may be combined with any of the preceding embodiments, the isolated CD45 + The population of cells comprises a ratio of Tmem to memory Treg of about 27:1 to about 9:10. In some embodiments that may be combined with any of the preceding embodiments, the isolated CD45 + The population of cells comprises a ratio of Tcon to memory Treg of less than 1:1, less than 1:2, less than 1:3, less than 1:4, less than 1:5, less than 1:6, less than 1:7, less than 1:8, less than 1:9, less than 1:10, less than 1:20, less than 1:30, less than 1:40, less than 1:50, less than 1:60, less than 1:70, less than 1:80, less than 1:90, or less than 1:100. In some embodiments that may be combined with any of the preceding embodiments, the Tcon is TCRα + , TCRβ + , or TCRα + TCRβ + In some embodiments that may be combined with any of the preceding embodiments, Tcon is CD25 - , CD127 + , or CD25 - CD127 + In some embodiments that may be combined with any of the preceding embodiments, Tcon is TCRα + TCRβ + CD45RA + CD45RO - CD25 - CD95 - IL-2Rβ - CD127 + In some embodiments that may be combined with any of the preceding embodiments, the iNKT is CD1d-tet + , 6B11 + , or CD1d-tet + 6B11 +In some embodiments that may be combined with any of the preceding embodiments, the product further comprises a pharmaceutical composition comprising one or more doses of a graft-versus-host disease (GVHD) prophylactic agent. In some embodiments that may be combined with any of the preceding embodiments, the GVHD prophylactic agent is tacrolimus. In some embodiments that may be combined with any of the preceding embodiments, one or more doses of tacrolimus are provided to maintain a trough blood concentration of about 5 ng / mL to about 10 ng / mL in the human subject receiving the product. In some embodiments that may be combined with any of the preceding embodiments, the pharmaceutical composition comprises tacrolimus in a twice-daily dose ranging from about 0.01 mg per kilogram of body weight of the human subject receiving the product to about 0.50 mg per kilogram of body weight of the human subject receiving the product. In some embodiments that may be combined with any of the preceding embodiments, the tacrolimus is isolated CD45 + The population of cells is administered in an amount to maintain or will maintain a target blood concentration of about 1 ng / mL to about 10 ng / mL in the human subject receiving the product for about 20 days or more, about 25 days or more, about 30 days or more, about 35 days or more, about 40 days or more, about 45 days or more, about 50 days or more, about 55 days or more, about 60 days or more, about 65 days or more, about 70 days or more, about 75 days or more, about 80 days or more, about 85 days or more, about 90 days or more, about 95 days or more, about 100 days or more, about 110 days or more, about 120 days or more, about 130 days or more, about 140 days or more, or about 150 days or more after administration. In some embodiments that may be combined with any of the preceding embodiments, the isolated CD45 + The population of cells contains less than about 5 EU to about 0.5 EU endotoxin per mL of formulation.

[0034] In some embodiments that may be combined with any of the preceding embodiments, the HSPCs, Tmems, Tregs, or any combination thereof are obtained from an allogeneic donor that is HLA-matched relative to the human subject receiving the product. In some embodiments that may be combined with any of the preceding embodiments, the isolated CD45 +The population of cells is derived from an allogeneic donor that is HLA-matched relative to the human subject receiving the product. In some embodiments that may be combined with any of the preceding embodiments, the HSPCs, Tmems, Tregs, or any combination thereof are obtained from an allogeneic donor that has at least one HLA mismatch relative to the human subject receiving the product. In some embodiments that may be combined with any of the preceding embodiments, the isolated CD45 + The population of cells is derived from an allogeneic donor with at least one HLA mismatch relative to the human subject receiving the product. In some embodiments that may be combined with any of the preceding embodiments, the at least one HLA mismatch is at an allele selected from HLA-A, HLA-B, HLA-C, HLA-DRB1, and any combination thereof. In some embodiments that may be combined with any of the preceding embodiments, the cells with at least one HLA mismatch are derived from a donor that is 6 / 8 HLA mismatched relative to the human subject receiving the product, or a donor that is 7 / 8 HLA mismatched relative to the human subject receiving the product.

[0035] In some embodiments that may be combined with any of the preceding embodiments, the cells with at least one HLA mismatch are derived from a donor that is 7 / 8 HLA mismatched relative to the human subject receiving the product. In some embodiments that may be combined with any of the preceding embodiments, the donor that is 7 / 8 HLA mismatched relative to the human subject receiving the product has a mismatch in HLA-A. In some embodiments that may be combined with any of the preceding embodiments, the donor that is 7 / 8 HLA mismatched relative to the human subject receiving the product has a mismatch in HLA-B. In some embodiments that may be combined with any of the preceding embodiments, the donor that is 7 / 8 HLA mismatched relative to the human subject receiving the product has a mismatch in HLA-C. In some embodiments that may be combined with any of the preceding embodiments, the donor that is 7 / 8 HLA mismatched relative to the human subject receiving the product has a mismatch in HLA-DRB1. In some embodiments that may be combined with any of the preceding embodiments, the donor has at least one HLA mismatch compared to the human subject receiving the product because the donor is homozygous for the HLA allele but the human subject receiving the product is heterozygous for the HLA allele, and therefore has a mismatched HLA allele. In some embodiments that may be combined with any of the preceding embodiments, the donor has at least one HLA mismatch compared to the human subject receiving the product because the donor is heterozygous for the HLA allele but the human subject receiving the product is homozygous for the HLA allele. In some embodiments that may be combined with any of the preceding embodiments, the donor has at least one HLA mismatch compared to the human subject receiving the product because the donor is heterozygous for the HLA allele but the human subject receiving the product is homozygous for the HLA allele, and therefore has a mismatched HLA allele. In some embodiments that may be combined with any of the preceding embodiments, the HSPCs, Tmems, Tregs, or any combination thereof, are obtained from a half-matched allogeneic donor compared to the human subject receiving the product. In some embodiments that may be combined with any of the preceding embodiments, isolated CD45 +The population of cells is derived from a half-matched allogeneic donor compared to the human subject receiving the product. In some embodiments that may be combined with any of the preceding embodiments, the allogeneic donor is related to the human subject receiving the product. In some embodiments that may be combined with any of the preceding embodiments, the allogeneic donor is unrelated to the human subject receiving the product. In some embodiments that may be combined with any of the preceding embodiments, the body weight of the human subject receiving the product is an actual body weight. In some embodiments that may be combined with any of the preceding embodiments, the body weight of the human subject receiving the product is an ideal body weight. In some embodiments, the cell therapy product of any one of the preceding embodiments, or any combination thereof, is for use in a method of treating a human subject having or suspected of having a malignant hematological disorder. In some embodiments, the hematological malignancy is selected from leukemia, acute leukemia, acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), mixed phenotype acute leukemia (MPAL), chronic myeloid leukemia (CML), multiple myeloma, lymphoma, Hodgkin's lymphoma, non-Hodgkin's lymphoma, myelodysplastic syndrome (MDS), myeloproliferative syndrome, myelofibrosis, and blastic plasmacytoid dendritic cell neoplasm (BPDCN). In some embodiments, the cell therapy product of any one of the preceding embodiments, or any combination thereof, is for use in a method of treating a human subject having or suspected of having an autoimmune disorder. In some embodiments, the autoimmune disorder is multiple sclerosis.

[0036] Another aspect of the present disclosure relates to a method of treating a human subject having or suspected of having acute leukemia that is in complete remission, the method comprising administering an isolated CD45 + administering to a human subject a cell therapy product comprising a population of isolated CD45 cells. + The cell population is CD34 + Enriched population of hematopoietic stem and progenitor cells (HSPCs), CD45RA - Enriched populations of memory T cells (Tmem), and fresh CD4 + CD25 + CD127 dimContains an enriched population of regulatory T cells (Tregs), isolated CD45 + The population of cells is approximately 5.0 x 10 per kilogram of body weight of the human subject receiving the product. 5 < naive conventional CD3 + CD25 - CD45RA + T cells (Tcon), approximately 6.0×10 7 < 100 total naive conventional CD3 + CD25 - CD45RA + T cells (Tcon), or approximately 1.0 × 10 6 < 100 total naive conventional CD3 + CD25 - CD45RA + Naive conventional CD3 to contain T cells (Tcon) + CD25 - CD45RA + T cells (Tcon) are depleted. Another aspect of the present disclosure relates to a method for treating a human subject having or suspected of having acute leukemia in complete remission, the method comprising administering to the human subject a cell therapy product of the present disclosure. In some embodiments that may be combined with any of the preceding embodiments, the human subject has a blast load of about 5% or less in their bone marrow. In some embodiments that may be combined with any of the preceding embodiments, the human subject has no circulating blasts and / or blasts with Auer rods. In some embodiments that may be combined with any of the preceding embodiments, the human subject has no extramedullary disease. In some embodiments that may be combined with any of the preceding embodiments, the human subject has a blast load of about 1.0 x 10 9 In some embodiments that may be combined with any of the preceding embodiments, the human subject has an absolute neutrophil count (ANC) of about 1.0 x 10 / L or greater. 11 / L or greater. In some embodiments that may be combined with any of the preceding embodiments, the human subject is red blood cell transfusion independent. In some embodiments that may be combined with any of the preceding embodiments, the acute leukemia is in complete remission with incomplete hematologic recovery. In some embodiments that may be combined with any of the preceding embodiments, the human subject has residual neutropenia. In some embodiments that may be combined with any of the preceding embodiments, the human subject has a platelet count of about 1.0 x 10 9 In some embodiments that may be combined with any of the preceding embodiments, the human subject has an absolute neutrophil count (ANC) of about 1.0 x 10 / L or less. In some embodiments that may be combined with any of the preceding embodiments, the human subject has residual thrombocytopenia. In some embodiments that may be combined with any of the preceding embodiments, the human subject has an absolute neutrophil count (ANC) of about 1.0 x 10 / L or less. 11 Have a platelet count of ≤ 1 / L.

[0037] Another aspect of the present disclosure relates to a method of treating a human subject having or suspected of having active acute leukemia, the method comprising administering an isolated CD45 + administering to a human subject a cell therapy product comprising a population of isolated CD45 cells. + The cell population is CD34 + Enriched population of hematopoietic stem and progenitor cells (HSPCs), CD45RA - Enriched populations of memory T cells (Tmem), and fresh CD4 + CD25 + CD127 dim Contains an enriched population of regulatory T cells (Tregs), isolated CD45 + The population of cells is approximately 5.0 x 10 per kilogram of body weight of the human subject receiving the product. 5 < naive conventional CD3 + CD25 - CD45RA + T cells (Tcon), approximately 6.0×10 7 < 100 total naive conventional CD3 + CD25 - CD45RA + T cells (Tcon), or approximately 1.0 × 10 6 < 100 total naive conventional CD3+ CD25 - CD45RA + Naive conventional CD3 to contain T cells (Tcon) + CD25 - CD45RA + T cells (Tcon) are depleted. Another aspect of the present disclosure relates to a method for treating a human subject having or suspected of having active acute leukemia, the method comprising administering a cell therapy product of the present disclosure to the human subject. In some embodiments that may be combined with any of the preceding embodiments, the human subject has a leukemic blast infiltration of about 10% or less of the bone marrow. In some embodiments that may be combined with any of the preceding embodiments, the acute leukemia is acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), and / or mixed phenotype acute leukemia (MPAL).

[0038] Another aspect of the present disclosure relates to a method of treating a human subject having or suspected of having chronic myeloid leukemia (CML), the method comprising administering to a subject an isolated CD45 + administering to a human subject a cell therapy product comprising a population of isolated CD45 cells. + The cell population is CD34 + Enriched population of hematopoietic stem and progenitor cells (HSPCs), CD45RA - Enriched populations of memory T cells (Tmem), and fresh CD4 + CD25 + CD127 dim Contains an enriched population of regulatory T cells (Tregs), isolated CD45 + The population of cells is approximately 5.0 x 10 per kilogram of body weight of the human subject receiving the product. 5 < naive conventional CD3 + CD25 - CD45RA + T cells (Tcon), approximately 6.0×10 7 < 100 total naive conventional CD3 + CD25 - CD45RA + T cells (Tcon), or approximately 1.0 × 10 6 < 100 total naive conventional CD3+ CD25 - CD45RA + Naive conventional CD3 to contain T cells (Tcon) + CD25 - CD45RA + T cells (Tcon) are depleted. Another aspect of the present disclosure relates to a method for treating a human subject having or suspected of having chronic myeloid leukemia (CML), the method comprising administering to the human subject a cell therapy product of the present disclosure. In some embodiments that may be combined with any of the preceding embodiments, the human subject is in a myeloblastic and / or lymphoblastic blast crisis. In some embodiments that may be combined with any of the preceding embodiments, the blastic blast crisis is in complete remission. In some embodiments that may be combined with any of the preceding embodiments, the blastic blast crisis is in complete remission with incomplete hematologic recovery. In some embodiments that may be combined with any of the preceding embodiments, the CML is in accelerated phase. In some embodiments that may be combined with any of the preceding embodiments, the CML is in chronic phase. In some embodiments that may be combined with any of the preceding embodiments, the chronic phase CML is resistant to or intolerant of one or more first- or second-generation tyrosine kinase inhibitors (TKIs).

[0039] Another aspect of the present disclosure relates to a method of treating a human subject having or suspected of having high-risk or very high-risk myelodysplastic syndrome (MDS), the method comprising administering to a subject an isolated CD45 + administering to a human subject a cell therapy product comprising a population of isolated CD45 cells. + The cell population is CD34 + Enriched population of hematopoietic stem and progenitor cells (HSPCs), CD45RA - Enriched populations of memory T cells (Tmem), and fresh CD4 + CD25 + CD127 dim Contains an enriched population of regulatory T cells (Tregs), isolated CD45 +The population of cells is approximately 5.0 x 10 per kilogram of body weight of the human subject receiving the product. 5 < naive conventional CD3 + CD25 - CD45RA + T cells (Tcon), approximately 6.0×10 7 < 100 total naive conventional CD3 + CD25 - CD45RA + T cells (Tcon), or approximately 1.0 × 10 6 < 100 total naive conventional CD3 + CD25 - CD45RA + Naive conventional CD3 to contain T cells (Tcon) + CD25 - CD45RA + T cells (Tcon) are depleted. Another aspect of the present disclosure relates to a method for treating a human subject having or suspected of having high-risk or very high-risk myelodysplastic syndrome (MDS), the method comprising administering to the human subject a cell therapy product of the present disclosure. In some embodiments, the human subject has a blast load of about 10% or less in their bone marrow.

[0040] Another aspect of the present disclosure relates to a method of treating a human subject having or suspected of having myelofibrosis, the method comprising administering an isolated CD45 + administering to a human subject a cell therapy product comprising a population of isolated CD45 cells. + The cell population is CD34 + Enriched population of hematopoietic stem and progenitor cells (HSPCs), CD45RA - Enriched populations of memory T cells (Tmem), and fresh CD4 + CD25 + CD127 dim Contains an enriched population of regulatory T cells (Tregs), isolated CD45 + The population of cells is approximately 5.0 x 10 per kilogram of body weight of the human subject receiving the product. 5 < naive conventional CD3 + CD25 - CD45RA +T cells (Tcon), approximately 6.0×10 7 < 100 total naive conventional CD3 + CD25 - CD45RA + T cells (Tcon), or approximately 1.0 × 10 6 < 100 total naive conventional CD3 + CD25 - CD45RA + Naive conventional CD3 to contain T cells (Tcon) + CD25 - CD45RA + T cells (Tcon) are depleted. Another aspect of the present disclosure relates to a method for treating a human subject having or suspected of having myelofibrosis, the method comprising administering a cell therapy product of the present disclosure to the human subject. In some embodiments that may be combined with any of the preceding embodiments, the myelofibrosis is eligible for standard myeloablative allogeneic hematopoietic stem cell transplantation (alloHSCT). In some embodiments that may be combined with any of the preceding embodiments, the myelofibrosis is intermediate-2 risk myelofibrosis or high-risk myelofibrosis. In some embodiments that may be combined with any of the preceding embodiments, the myelofibrosis is intermediate-1 risk myelofibrosis, which is associated with a high symptom burden, low platelet count, and / or complex cytogenetics.

[0041] Another aspect of the present disclosure relates to a method of treating a human subject having or suspected of having a malignant hematological disorder, the method comprising administering to a subject an isolated CD45 + administering to a human subject a cell therapy product comprising a population of isolated CD45 cells. + The cell population is CD34 + Enriched population of hematopoietic stem and progenitor cells (HSPCs), CD45RA - Enriched populations of memory T cells (Tmem), and fresh CD4 + CD25 + CD127 dim Contains an enriched population of regulatory T cells (Tregs), isolated CD45 + The population of cells is approximately 5.0 x 10 per kilogram of body weight of the human subject receiving the product. 5< naive conventional CD3 + CD25 - CD45RA + T cells (Tcon), approximately 6.0×10 7 < 100 total naive conventional CD3 + CD25 - CD45RA + T cells (Tcon), or approximately 1.0 × 10 6 < 100 total naive conventional CD3 + CD25 - CD45RA + Naive conventional CD3 to contain T cells (Tcon) + CD25 - CD45RA + T cells (Tcon) are depleted.

[0042] In some embodiments that may be combined with any of the preceding embodiments, the cell therapy product comprises a cell therapy product of the present disclosure. In some embodiments that may be combined with any of the preceding embodiments, the malignant hematologic disease is selected from leukemia, acute leukemia, acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), mixed phenotype acute leukemia (MPAL), chronic myeloid leukemia (CML), multiple myeloma, lymphoma, Hodgkin's lymphoma, non-Hodgkin's lymphoma, myelodysplastic syndrome (MDS), myeloproliferative syndrome, myelofibrosis, and blastic plasmacytoid dendritic cell neoplasm (BPDCN). In some embodiments that may be combined with any of the preceding embodiments, the method further comprises administering one or more doses of a graft-versus-host disease (GVHD) prophylactic agent. In some embodiments that may be combined with any of the preceding embodiments, the GVHS prophylactic agent is tacrolimus. In some embodiments that may be combined with any of the preceding embodiments, tacrolimus is provided in an amount sufficient to maintain a trough blood concentration of about 5 ng / mL to about 10 ng / mL in the human subject. In some embodiments that may be combined with any of the preceding embodiments, tacrolimus is provided twice daily at a dose ranging from about 0.01 mg per kilogram of body weight of the human subject to 0.50 mg per kilogram of body weight of the human subject. In some embodiments that may be combined with any of the preceding embodiments, tacrolimus inhibits CD45 +or about 150 days or more after administration of the third population of cells, in an amount to maintain or maintain a target blood concentration of about 1 ng / mL to about 10 ng / mL in the human subject for about 20 days or more, about 25 days or more, about 30 days or more, about 35 days or more, about 40 days or more, about 55 days or more, about 50 days or more, about 55 days or more, about 60 days or more, about 65 days or more, about 770 days or more, about 75 days or more, about 80 days or more, about 85 days or more, about 90 days or more, about 95 days or more, about 100 days or more, about 110 days or more, about 120 days or more, about 130 days or more, about 140 days or more, or about 150 days or more. In some embodiments that may be combined with any of the preceding embodiments, tacrolimus is initially administered about 12 hours to about 24 hours after administration of the cell therapy product. In some embodiments that may be combined with any of the preceding embodiments, the administration of tacrolimus begins to taper about 90 days after the initial administration of tacrolimus. In some embodiments that may be combined with any of the preceding embodiments, the administration comprises administering to the human subject an isolated CD45 + In some embodiments that may be combined with any of the preceding embodiments, the method comprises injecting an isolated CD45 cell population into the target cell. + The cell population is approximately 1.0 x 10 per kilogram of body weight in a human subject. 5 ~Approx. 1.0×10 8 HSPCs, or approximately 5.0 x 10 5 ~Approx. 1.5×10 10 In some embodiments that may be combined with any of the preceding embodiments, the isolated CD45 HSPCs + The cell population is approximately 1.0 x 10 per kilogram of body weight in a human subject. 5 ≥ 2.0 x 10 HSPCs per kilogram of body weight in a human subject 5 ≥ 3.0 x 10 HSPCs per kilogram of body weight in a human subject 5 ≥ 4.0 x 10 HSPCs per kilogram of body weight in a human subject 5 ≥ 5.0 x 10 HSPCs per kilogram of body weight in a human subject 5 ≥ 6.0 x 10 HSPCs per kilogram of body weight in a human subject 5 ≥ 7.0 x 10 HSPCs per kilogram of body weight in a human subject5 ≥ 8.0 x 10 HSPCs per kilogram of body weight in a human subject 5 ≥ 9.0 x 10 HSPCs per kilogram of body weight in a human subject 5 ≥ 1.0 x 10 HSPCs per kilogram of body weight in a human subject 6 ≥ 1.5 x 10 HSPCs per kilogram of body weight in a human subject 6 ≥ 2.0 x 10 HSPCs per kilogram of body weight in a human subject 6 ≥ 2.5 x 10 HSPCs per kilogram of body weight in a human subject 6 ≥ 3.0 x 10 HSPCs per kilogram of body weight in a human subject 6 ≥ 3.5 x 10 HSPCs per kilogram of body weight in a human subject 6 ≥ 4.0 x 10 HSPCs per kilogram of body weight in a human subject 6 ≥ 4.5 x 10 HSPCs per kilogram of body weight in a human subject 6 ≥ 5.0 x 10 HSPCs per kilogram of body weight in a human subject 6 ≥ 5.5 x 10 HSPCs per kilogram of body weight in a human subject 6 ≥ 6.0 x 10 HSPCs per kilogram of body weight in a human subject 6 ≥ 6.5 x 10 HSPCs per kilogram of body weight in a human subject 6 ≥ 7.0 x 10 HSPCs per kilogram of body weight in a human subject 6 ≥ 7.5 x 10 HSPCs per kilogram of body weight in a human subject 6 ≥ 8.0 x 10 HSPCs per kilogram of body weight in a human subject 6 ≥ 8.5 x 10 HSPCs per kilogram of body weight in a human subject 6 ≥ 9.0 x 10 HSPCs per kilogram of body weight in a human subject 6 ≥ 9.5 x 10 HSPCs per kilogram of body weight in a human subject 6 ≥ 1.0 x 10 HSPCs per kilogram of body weight in a human subject 7 ≥ 1.5 x 10 HSPCs per kilogram of body weight in a human subject 7≥ 2.0 x 10 HSPCs per kilogram of body weight in a human subject 7 ≥ 2.5 x 10 HSPCs per kilogram of body weight in a human subject 7 ≥ 3.0 x 10 HSPCs per kilogram of body weight in a human subject 7 ≥ 3.5 x 10 HSPCs per kilogram of body weight in a human subject 7 ≥ 4.0 x 10 HSPCs per kilogram of body weight in a human subject 7 ≥ 4.5 x 10 HSPCs per kilogram of body weight in a human subject 7 ≥ 5.0 x 10 HSPCs per kilogram of body weight in a human subject 7 ≥ 5.5 x 10 HSPCs per kilogram of body weight in a human subject 7 ≥ 6.0 x 10 HSPCs per kilogram of body weight in a human subject 7 ≥ 6.5 x 10 HSPCs per kilogram of body weight in a human subject 7 ≥ 7.0 x 10 HSPCs per kilogram of body weight in a human subject 7 ≥ 7.5 x 10 HSPCs per kilogram of body weight in a human subject 7 ≥ 8.0 x 10 HSPCs per kilogram of body weight in a human subject 7 ≥ 8.5 x 10 HSPCs per kilogram of body weight in a human subject 7 ≥ 9.0 x 10 HSPCs per kilogram of body weight in a human subject 7 ≥ 9.5 x 10 HSPCs per kilogram of body weight in a human subject 7 HSPCs or approximately 1.0 x 10 per kilogram of body weight in a human subject 8 In some embodiments that may be combined with any of the preceding embodiments, the isolated CD45 + The cells were approximately 5.0 × 10 5 More than 6.0 x 10 HSPCs 5 More than 7.0 x 10 HSPCs 5 More than HSPCs, approximately 8.0 x 10 5 More than 9.0 x 10 HSPCs 5 More than 1.0 x 10 HSPCs 6More than 1.5 x 10 HSPCs 6 More than HSPCs, approximately 2.0 x 10 6 More than HSPCs, approximately 2.5 x 10 6 More than 3.0 x 10 HSPCs 6 More than HSPCs, approximately 3.5 x 10 6 More than HSPCs, approximately 4.0 x 10 6 More than HSPCs, approximately 4.5 x 10 6 More than 5.0 x 10 HSPCs 6 More than 5.5 x 10 HSPCs 6 More than 6.0 x 10 HSPCs 6 More than 6.5 x 10 HSPCs 6 More than 7.0 x 10 HSPCs 6 More than 7.5 x 10 HSPCs 6 More than HSPCs, approximately 8.0 x 10 6 More than HSPCs, approximately 8.5 x 10 6 More than 9.0 x 10 HSPCs 6 More than 9.5 x 10 HSPCs 6 More than 1.0 x 10 HSPCs 7 More than 1.5 x 10 HSPCs 7 More than HSPC, approximately 2.0x10 7 More than HSPCs, approximately 2.5 x 10 7 More than 3.0 x 10 HSPCs 7 More than HSPCs, approximately 3.5 x 10 7 More than HSPCs, approximately 4.0 x 10 7 More than HSPCs, approximately 4.5 x 10 7 More than 5.0 x 10 HSPCs 7 More than 5.5 x 10 HSPCs 7 More than 6.0 x 10 HSPCs 7 More than 6.5 x 10 HSPCs 7 More than 7.0 x 10 HSPCs 7 More than 7.5 x 10 HSPCs 7 More than HSPCs, approximately 8.0 x 10 7 More than HSPCs, approximately 8.5 x 10 7 More than 9.0 x 10 HSPCs 7More than 9.5 x 10 HSPCs 7 More than 1.0 x 10 HSPCs 8 More than 1.5 x 10 HSPCs 8 More than HSPCs, approximately 2.0 x 10 8 More than HSPCs, approximately 2.5 x 10 8 More than 3.0 x 10 HSPCs 8 More than HSPCs, approximately 3.5 x 10 8 More than HSPCs, approximately 4.0 x 10 8 More than HSPCs, approximately 4.5 x 10 8 More than 5.0 x 10 HSPCs 8 More than 5.5 x 10 HSPCs 8 More than 6.0 x 10 HSPCs 8 More than 6.5 x 10 HSPCs 8 More than 7.0 x 10 HSPCs 8 More than 7.5 x 10 HSPCs 8 More than HSPCs, approximately 8.0 x 10 8 More than HSPCs, approximately 8.5 x 10 8 More than 9.0 x 10 HSPCs 8 More than 9.5 x 10 HSPCs 8 More than 1.0 x 10 HSPCs 9 More than 1.5 x 10 HSPCs 9 More than HSPCs, approximately 2.0 x 10 9 More than HSPCs, approximately 2.5 x 10 9 More than 3.0 x 10 HSPCs 9 More than HSPCs, approximately 3.5 x 10 9 More than HSPCs, approximately 4.0 x 10 9 More than HSPCs, approximately 4.5 x 10 9 More than 5.0 x 10 HSPCs 9 More than 5.5 x 10 HSPCs 9 More than 6.0 x 10 HSPCs 9 More than 6.5 x 10 HSPCs 9 More than 7.0 x 10 HSPCs 9 More than 7.5 x 10 HSPCs 9 More than HSPCs, approximately 8.0 x 10 9More than HSPCs, approximately 8.5 x 10 9 More than 9.0 x 10 HSPCs 9 More than 9.5 x 10 HSPCs 9 More than 1.0 x 10 HSPCs 10 or more HSPCs, or approximately 1.5 x 10 10 In some embodiments that may be combined with any of the preceding embodiments, the isolated CD45 + The cell population was approximately 5.0 × 10 5 ~Approx. 1.5×10 10 Approximately 1.0 x 10 per kilogram of body weight of a human subject receiving Tmem's product 5 ~Approx. 1.0×10 8 In some embodiments that may be combined with any of the preceding embodiments, isolated CD45 + The population of cells is 1 kg body weight of the human subject receiving the product. Approximately 1.0 x 10 per 5 ≥ 2.0 x 10 Tmems per kilogram of body weight of the human subject receiving the product 5 ≥ 3.0 x 10 Tmems per kilogram of body weight of the human subject receiving the product 5 or more Tmems, approximately 4.0 x 10 per kilogram of body weight of the human subject receiving the product 5 or more Tmems, approximately 5.0 x 10 per kilogram of body weight of the human subject receiving the product 5 ≥ 6.0 x 10 Tmems per kilogram of body weight of the human subject receiving the product 5 ≥ 7.0 x 10 Tmems per kilogram of body weight of the human subject receiving the product 5 ≥ 8.0 x 10 Tmems per kilogram of body weight of the human subject receiving the product 5 or more Tmems, approximately 9.0 x 10 per kilogram of body weight of the human subject receiving the product 5 or more Tmems, approximately 1.0 x 10 per kilogram of body weight of the human subject receiving the product 6 ≥ 1.5 x 10 Tmems per kilogram of body weight of the human subject receiving the product 6≥ 2.0 x 10 Tmems per kilogram of body weight of the human subject receiving the product 6 ≥ 2.5 x 10 Tmems per kilogram of body weight of the human subject receiving the product 6 ≥ 3.0 x 10 Tmems per kilogram of body weight of the human subject receiving the product 6 ≥ 3.5 x 10 Tmems per kilogram of body weight of the human subject receiving the product 6 or more Tmems, approximately 4.0 x 10 per kilogram of body weight of the human subject receiving the product 6 or more Tmems, approximately 4.5 x 10 per kilogram of body weight of the human subject receiving the product 6 or more Tmems, approximately 5.0 x 10 per kilogram of body weight of the human subject receiving the product 6 or more Tmems, approximately 5.5 x 10 per kilogram of body weight of the human subject receiving the product 6 ≥ 6.0 x 10 Tmems per kilogram of body weight of the human subject receiving the product 6 or more Tmems, approximately 6.5 x 10 per kilogram of body weight of the human subject receiving the product 6 ≥ 7.0 x 10 Tmems per kilogram of body weight of the human subject receiving the product 6 ≥ 7.5 x 10 Tmems per kilogram of body weight of the human subject receiving the product 6 ≥ 8.0 x 10 Tmems per kilogram of body weight of the human subject receiving the product 6 ≥ 8.5 x 10 Tmems per kilogram of body weight of the human subject receiving the product 6 or more Tmems, approximately 9.0 x 10 per kilogram of body weight of the human subject receiving the product 6 or more Tmems, approximately 9.5 x 10 per kilogram of body weight of the human subject receiving the product 6 or more Tmems, approximately 1.0 x 10 per kilogram of body weight of the human subject receiving the product 7 ≥ 1.5 x 10 Tmems per kilogram of body weight of the human subject receiving the product 7 ≥ 2.0 x 10 Tmems per kilogram of body weight of the human subject receiving the product 7≥ 2.5 x 10 Tmems per kilogram of body weight of the human subject receiving the product 7 ≥ 3.0 x 10 Tmems per kilogram of body weight of the human subject receiving the product 7 ≥ 3.5 x 10 Tmems per kilogram of body weight of the human subject receiving the product 7 or more Tmems, approximately 4.0 x 10 per kilogram of body weight of the human subject receiving the product 7 or more Tmems, approximately 4.5 x 10 per kilogram of body weight of the human subject receiving the product 7 or more Tmems, approximately 5.0 x 10 per kilogram of body weight of the human subject receiving the product 7 or more Tmems, approximately 5.5 x 10 per kilogram of body weight of the human subject receiving the product 7 ≥ 6.0 x 10 Tmems per kilogram of body weight of the human subject receiving the product 7 or more Tmems, approximately 6.5 x 10 per kilogram of body weight of the human subject receiving the product 7 ≥ 7.0 x 10 Tmems per kilogram of body weight of the human subject receiving the product 7 ≥ 7.5 x 10 Tmems per kilogram of body weight of the human subject receiving the product 7 ≥ 8.0 x 10 Tmems per kilogram of body weight of the human subject receiving the product 7 ≥ 8.5 x 10 Tmems per kilogram of body weight of the human subject receiving the product 7 or more Tmems, approximately 9.0 x 10 per kilogram of body weight of the human subject receiving the product 7 or more Tmems, approximately 9.5 x 10 per kilogram of body weight of the human subject receiving the product 7 or more than 1.0 x 10 per kilogram of body weight of the human subject receiving the product 8 In some embodiments that may be combined with any of the preceding embodiments, the isolated CD45 + The cell population was approximately 5.0 × 10 5 More than 6.0 × 10 Tmem 5 More than 7.0 × 10 Tmem 5 More than 8.0 × 10 Tmem 5More than 9.0×10 Tmem 5 More than 1.0×10 Tmem 6 More than 1.5×10 Tmem 6 More than 10 Tmem, approximately 2.0 x 10 6 More than 10 Tmem, approximately 2.5 x 10 6 More than 3.0 × 10 Tmem 6 More than 3.5 × 10 Tmem 6 More than 4.0 × 10 Tmem 6 More than 4.5 × 10 Tmem 6 More than 5.0 × 10 Tmem 6 More than 5.5×10 Tmem 6 More than 6.0 × 10 Tmem 6 More than 6.5×10 Tmem 6 More than 7.0 × 10 Tmem 6 More than 7.5×10 Tmem 6 More than 8.0 × 10 Tmem 6 More than 8.5×10 Tmem 6 More than 9.0×10 Tmem 6 More than 9.5×10 Tmem 6 More than 1.0×10 Tmem 7 More than 1.5×10 Tmem 7 More than 10 Tmem, approximately 2.0 x 10 7 More than 10 Tmem, approximately 2.5 x 10 7 More than 3.0 × 10 Tmem 7 More than 3.5 × 10 Tmem 7 More than 4.0 × 10 Tmem 7 More than 4.5 × 10 Tmem 7 More than 5.0 × 10 Tmem 7 More than 5.5×10 Tmem 7 More than 6.0 × 10 Tmem 7 More than 6.5×10 Tmem 7 More than 7.0 × 10 Tmem 7 More than 7.5×10 Tmem 7 More than 8.0 × 10 Tmem 7More than 8.5×10 Tmem 7 More than 9.0×10 Tmem 7 More than 9.5×10 Tmem 7 More than 1.0×10 Tmem 8 More than 1.5×10 Tmem 8 More than 10 Tmem, approximately 2.0 x 10 8 More than 10 Tmem, approximately 2.5 x 10 8 More than 3.0 × 10 Tmem 8 More than 3.5 × 10 Tmem 8 More than 4.0 × 10 Tmem 8 More than 4.5 × 10 Tmem 8 More than 5.0 × 10 Tmem 8 More than 5.5×10 Tmem 8 More than 6.0 × 10 Tmem 8 More than 6.5×10 Tmem 8 More than 7.0 × 10 Tmem 8 More than 7.5×10 Tmem 8 More than 8.0 × 10 Tmem 8 More than 8.5×10 Tmem 8 More than 9.0×10 Tmem 8 More than 9.5×10 Tmem 8 More than 1.0×10 Tmem 9 More than 1.5×10 Tmem 9 More than 10 Tmem, approximately 2.0 x 10 9 More than 10 Tmem, approximately 2.5 x 10 9 More than 3.0 × 10 Tmem 9 More than 3.5 × 10 Tmem 9 More than 4.0 × 10 Tmem 9 More than 4.5 × 10 Tmem 9 More than 5.0 × 10 Tmem 9 More than 5.5×10 Tmem 9 More than 6.0 × 10 Tmem 9 More than 6.5×10 Tmem 9 More than 7.0 × 10 Tmem 9More than 7.5×10 Tmem 9 More than 8.0 × 10 Tmem 9 More than 8.5×10 Tmem 9 More than 9.0×10 Tmem 9 More than 9.5×10 Tmem 9 More than 1.0×10 Tmem 10 10 or more Tmem, or approximately 1.5 x 10 10 In some embodiments that may be combined with any of the preceding embodiments, the isolated CD45 + The cell population is approximately 1.0 x 10 per kilogram of body weight in a human subject. 5 ~Approx. 2.0×10 7 fresh Tregs or approximately 5.0 x 10 5 ~Approx. 3.0×10 9 In some embodiments that may be combined with any of the preceding embodiments, the isolated CD45 + The cell population is approximately 1.0 x 10 per kilogram of body weight in a human subject. 5 ≥ 2.0 x 10 fresh Tregs per kilogram of body weight in a human subject 5 ≥ 3.0 x 10 fresh Tregs per kilogram of body weight in a human subject 5 ≥ 4.0 x 10 fresh Tregs per kilogram of body weight in a human subject 5 ≥ 5.0 x 10 fresh Tregs per kilogram of body weight in a human subject 5 ≥ 6.0 x 10 fresh Tregs per kilogram of body weight in a human subject 5 More than 7.0 x 10 fresh Tregs per kilogram of body weight in a human subject 5 ≥ 8.0 x 10 fresh Tregs per kilogram of body weight in a human subject 5 ≥ 9.0 x 10 fresh Tregs per kilogram of body weight in a human subject 5 ≥ 1.0 x 10 fresh Tregs per kilogram of body weight in a human subject 6 ≥ 1.5 x 10 fresh Tregs per kilogram of body weight in a human subject 6≥ 2.0 x 10 fresh Tregs per kilogram of body weight in a human subject 6 ≥ 2.5 x 10 fresh Tregs per kilogram of body weight in a human subject 6 ≥ 3.0 x 10 fresh Tregs per kilogram of body weight in a human subject 6 ≥ 3.5 x 10 fresh Tregs per kilogram of body weight in a human subject 6 ≥ 4.0 x 10 fresh Tregs per kilogram of body weight in a human subject 6 ≥ 4.5 x 10 fresh Tregs per kilogram of body weight in a human subject 6 ≥ 5.0 x 10 fresh Tregs per kilogram of body weight in a human subject 6 ≥ 5.5 x 10 fresh Tregs per kilogram of body weight in a human subject 6 ≥ 6.0 x 10 fresh Tregs per kilogram of body weight in a human subject 6 ≥ 6.5 x 10 fresh Tregs per kilogram of body weight in a human subject 6 More than 7.0 x 10 fresh Tregs per kilogram of body weight in a human subject 6 ≥ 7.5 x 10 fresh Tregs per kilogram of body weight in a human subject 6 ≥ 8.0 x 10 fresh Tregs per kilogram of body weight in a human subject 6 ≥ 8.5 x 10 fresh Tregs per kilogram of body weight in a human subject 6 ≥ 10 fresh Tregs , approximately 9.0 × 10 per kilogram of body weight in a human subject 6 ≥ 9.5 x 10 fresh Tregs per kilogram of body weight in a human subject 6 ≥ 1.0 x 10 fresh Tregs per kilogram of body weight in a human subject 7 ≥ 1.5 x 10 fresh Tregs per kilogram of body weight in a human subject 7 fresh Tregs or approximately 2.0 x 10 per kilogram of body weight in a human subject 7 In some embodiments that may be combined with any of the preceding embodiments, the isolated CD45 +The cell population was approximately 5.0 × 10 5 More than 6.0 x 10 fresh Tregs 5 More than 7.0 x 10 fresh Tregs 5 More than 8.0 x 10 fresh Tregs 5 More than 9.0 x 10 fresh Tregs 5 More than 1.0 x 10 fresh Tregs 6 More than 1.5 x 10 fresh Tregs 6 More than 2.0 x 10 fresh Tregs 6 More than 2.5 x 10 fresh Tregs 6 More than 3.0 x 10 fresh Tregs 6 More than 3.5 x 10 fresh Tregs 6 More than 4.0 x 10 fresh Tregs 6 More than 4.5 x 10 fresh Tregs 6 More than 5.0 x 10 fresh Tregs 6 More than 5.5 x 10 fresh Tregs 6 More than 6.0 x 10 fresh Tregs 6 More than 6.5 x 10 fresh Tregs 6 More than 7.0 x 10 fresh Tregs 6 More than 7.5 x 10 fresh Tregs 6 More than 8.0 x 10 fresh Tregs 6 More than 8.5 x 10 fresh Tregs 6 More than 9.0 x 10 fresh Tregs 6 More than 9.5 x 10 fresh Tregs 6 More than 1.0 x 10 fresh Tregs 7 More than 1.5 x 10 fresh Tregs 7 More than 2.0 x 10 fresh Tregs 7 More than 2.5 x 10 fresh Tregs 7 More than 3.0 x 10 fresh Tregs 7 More than 3.5 x 10 fresh Tregs 7 More than 4.0 x 10 fresh Tregs 7 More than 4.5 x 10 fresh Tregs 7More than 5.0 x 10 fresh Tregs 7 More than 5.5 x 10 fresh Tregs 7 More than 6.0 x 10 fresh Tregs 7 More than 6.5 x 10 fresh Tregs 7 More than 7.0 x 10 fresh Tregs 7 More than 7.5 x 10 fresh Tregs 7 More than 8.0 x 10 fresh Tregs 7 More than 8.5 x 10 fresh Tregs 7 More than 9.0 x 10 fresh Tregs 7 More than 9.5 x 10 fresh Tregs 7 More than 1.0 x 10 fresh Tregs 8 More than 1.5 x 10 fresh Tregs 8 More than 2.0 x 10 fresh Tregs 8 More than 2.5 x 10 fresh Tregs 8 More than 3.0 x 10 fresh Tregs 8 More than 3.5 x 10 fresh Tregs 8 More than 4.0 x 10 fresh Tregs 8 More than 4.5 x 10 fresh Tregs 8 More than 5.0 x 10 fresh Tregs 8 More than 5.5 x 10 fresh Tregs 8 More than 6.0 x 10 fresh Tregs 8 More than 6.5 x 10 fresh Tregs 8 More than 7.0 x 10 fresh Tregs 8 More than 7.5 x 10 fresh Tregs 8 More than 8.0 x 10 fresh Tregs 8 More than 8.5 x 10 fresh Tregs 8 More than 9.0 x 10 fresh Tregs 8 More than 9.5 x 10 fresh Tregs 8 More than 1.0 x 10 fresh Tregs 9 More than 1.5 x 10 fresh Tregs 9 More than 2.0 x 10 fresh Tregs 9More than 2.5 x 10 fresh Tregs 9 10 or more fresh Tregs, or approximately 3.0 x 10 9 In some embodiments that may be combined with any of the preceding embodiments, the isolated CD45 + The population of cells is approximately 5.0 x 10 per kilogram of body weight of the human subject receiving the product. 5 Less than approximately 4.5 x 10 per kilogram of body weight of the human subject receiving the product 5 Less than approximately 4.0 x 10 per kilogram of body weight of the human subject receiving the product 5 Less than approximately 3.5 x 10 per kilogram of body weight of the human subject receiving the product 5 Less than approximately 3.0 x 10 per kilogram of body weight of the human subject receiving the product 5 Less than approximately 2.5 x 10 per kilogram of body weight of the human subject receiving the product 5 Less than approximately 2.0 x 10 per kilogram of body weight of the human subject receiving the product 5 Less than approximately 1.5 x 10 per kilogram of body weight of the human subject receiving the product 5 Less than approximately 1.0 x 10 per kilogram of body weight of the human subject receiving the product 5 Less than approximately 9.5 x 10 per kilogram of body weight of the human subject receiving the product 4 Less than approximately 9.0 x 10 per kilogram of body weight of the human subject receiving the product 4 Less than approximately 8.5 x 10 per kilogram of body weight of the human subject receiving the product 4 Less than approximately 8.0 x 10 per kilogram of body weight of the human subject receiving the product 4 Less than approximately 7.5 x 10 per kilogram of body weight of the human subject receiving the product 4 Less than approximately 7.0 x 10 per kilogram of body weight of the human subject receiving the product 4 Less than approximately 6.5 x 10 per kilogram of body weight of the human subject receiving the product 4 Less than approximately 6.0 x 10 per kilogram of body weight of the human subject receiving the product 4Less than approximately 5.5 x 10 per kilogram of body weight of the human subject receiving the product 4 Less than approximately 5.0 x 10 per kilogram of body weight of the human subject receiving the product 4 Less than approximately 4.5 x 10 per kilogram of body weight of the human subject receiving the product 4 Less than approximately 4.0 x 10 per kilogram of body weight of the human subject receiving the product 4 Less than approximately 3.5 x 10 per kilogram of body weight of the human subject receiving the product 4 Less than approximately 3.0 x 10 per kilogram of body weight of the human subject receiving the product 4 Less than approximately 2.5 x 10 per kilogram of body weight of the human subject receiving the product 4 Less than approximately 2.0 x 10 per kilogram of body weight of the human subject receiving the product 4 Less than approximately 1.5 x 10 per kilogram of body weight of the human subject receiving the product 4 Less than approximately 1.0 x 10 per kilogram of body weight of the human subject receiving the product 4 Less than approximately 9.5 x 10 per kilogram of body weight of the human subject receiving the product 3 Less than approximately 9.0 x 10 per kilogram of body weight of the human subject receiving the product 3 Less than approximately 8.5 x 10 per kilogram of body weight of the human subject receiving the product 3 Less than approximately 8.0 x 10 per kilogram of body weight of the human subject receiving the product 3 Less than approximately 7.5 x 10 per kilogram of body weight of the human subject receiving the product 3 Less than approximately 7.0 x 10 per kilogram of body weight of the human subject receiving the product 3 Less than approximately 6.5 x 10 per kilogram of body weight of the human subject receiving the product 3 Less than approximately 6.0 x 10 per kilogram of body weight of the human subject receiving the product 3 Less than approximately 5.5 x 10 per kilogram of body weight of the human subject receiving the product 3Less than approximately 5.0 x 10 per kilogram of body weight of the human subject receiving the product 3 Less than approximately 4.5 x 10 per kilogram of body weight of the human subject receiving the product 3 Less than approximately 4.0 x 10 per kilogram of body weight of the human subject receiving the product 3 Less than approximately 3.5 x 10 per kilogram of body weight of the human subject receiving the product 3 Less than approximately 3.0 x 10 per kilogram of body weight of the human subject receiving the product 3 Less than approximately 2.5 x 10 per kilogram of body weight of the human subject receiving the product 3 Less than approximately 2.0 x 10 per kilogram of body weight of the human subject receiving the product 3 Less than approximately 1.5 x 10 per kilogram of body weight of the human subject receiving the product 3 Less than 1.0 x 10 per kilogram of body weight of the human subject receiving the product 3 In some embodiments that may be combined with any of the preceding embodiments, the isolated CD45 + The cell population was approximately 6.0 × 10 7 Less than 5.5 x 10 Tcon 7 Tcon less than 5.0 x 10 7 Less than 4.5 x 10 Tcon 7 Tcon less than 4.0 x 10 7 Less than 3.5 x 10 Tcon 7 Tcon less than 3.0 x 10 7 Less than 2.5 x 10 Tcon 7 Tcon less than 2.0 x 10 7 Less than 1.5 x 10 Tcon 7 Tcon less than 1.0 x 10 7 Less than 9.5 x 10 Tcon 6 Tcon less than 9.0 x 10 6 Less than 8.5 x 10 Tcon 6 Tcon less than 8.0 x 10 6 Less than 7.5 x 10 Tcon 6Tcon less than 7.0 x 10 6 Less than 6.5 x 10 Tcon 6 Tcon less than 6.0 x 10 6 Less than 5.5 x 10 Tcon 6 Tcon less than 5.0 x 10 6 Less than 4.5 x 10 Tcon 6 Tcon less than 4.0 x 10 6 Less than 3.5 x 10 Tcon 6 Tcon less than 3.0 x 10 6 Less than 2.5 x 10 Tcon 6 Tcon less than 2.0 x 10 6 Less than 1.5 x 10 Tcon 6 Less than 1.0 x 10 Tcon, or approximately 1.0 x 10 6 In some embodiments that may be combined with any of the preceding embodiments, the isolated CD45 + A population of cells expressing TCR Vα24Jα18 + CD127 + In some embodiments that may be combined with any of the preceding embodiments, the isolated CD45 + The population of cells is approximately 5.0 x 10 per kilogram of body weight of the human subject receiving the product. 2 ~Approx. 2.0×10 6 10 iNKT, or approximately 2.0 x 10 3 ~Approx. 4.0×10 8 In some embodiments that may be combined with any of the preceding embodiments, isolated CD45 + The population of cells is approximately 5.0 x 10 per kilogram of body weight of the human subject receiving the product. 2 6.0 x 10 iNKTs or more per kilogram of body weight of the human subject receiving the product 2 1 kg of body weight of human subject receiving the product Approximately 7.0 x 10 per 2 8.0 x 10 iNKTs or more per kilogram of body weight of the human subject receiving the product 2or more iNKT, approximately 9.0 x 10 per kilogram of body weight of the human subject receiving the product 2 or more iNKT, approximately 1.0 x 10 per kilogram of body weight of the human subject receiving the product 3 or more iNKT, approximately 2.0 x 10 per kilogram of body weight of the human subject receiving the product 3 or more iNKT, approximately 3.0 x 10 per kilogram of body weight of the human subject receiving the product 3 4.0 x 10 iNKTs or more per kilogram of body weight of the human subject receiving the product 3 or more iNKT, approximately 5.0 x 10 per kilogram of body weight of the human subject receiving the product 3 6.0 x 10 iNKTs or more per kilogram of body weight of the human subject receiving the product 3 7.0 x 10 iNKTs or more per kilogram of body weight of the human subject receiving the product 3 8.0 x 10 iNKTs or more per kilogram of body weight of the human subject receiving the product 3 or more iNKT, approximately 9.0 x 10 per kilogram of body weight of the human subject receiving the product 3 or more iNKT, approximately 1.0 x 10 per kilogram of body weight of the human subject receiving the product 4 or more iNKT, approximately 2.0 x 10 per kilogram of body weight of the human subject receiving the product 4 or more iNKT, approximately 3.0 x 10 per kilogram of body weight of the human subject receiving the product 4 4.0 x 10 iNKTs or more per kilogram of body weight of the human subject receiving the product 4 or more iNKT, approximately 5.0 x 10 per kilogram of body weight of the human subject receiving the product 4 6.0 x 10 iNKTs or more per kilogram of body weight of the human subject receiving the product 4 7.0 x 10 iNKTs or more per kilogram of body weight of the human subject receiving the product 4 8.0 x 10 iNKTs or more per kilogram of body weight of the human subject receiving the product 4 or more iNKT, approximately 9.0 x 10 per kilogram of body weight of the human subject receiving the product 4or more iNKT, approximately 1.0 x 10 per kilogram of body weight of the human subject receiving the product 5 or more iNKT, approximately 2.0 x 10 per kilogram of body weight of the human subject receiving the product 5 or more iNKT, approximately 3.0 x 10 per kilogram of body weight of the human subject receiving the product 5 4.0 x 10 iNKTs or more per kilogram of body weight of the human subject receiving the product 5 or more iNKT, approximately 5.0 x 10 per kilogram of body weight of the human subject receiving the product 5 6.0 x 10 iNKTs or more per kilogram of body weight of the human subject receiving the product 5 7.0 x 10 iNKTs or more per kilogram of body weight of the human subject receiving the product 5 8.0 x 10 iNKTs or more per kilogram of body weight of the human subject receiving the product 5 or more iNKT, approximately 9.0 x 10 per kilogram of body weight of the human subject receiving the product 5 or more iNKT, approximately 1.0 x 10 per kilogram of body weight of the human subject receiving the product 6 or more iNKT, approximately 1.5 x 10 per kilogram of body weight of the human subject receiving the product 6 or more than 2.0 x 10 iNKTs per kilogram of body weight of a human subject receiving the product 6 In some embodiments that may be combined with any of the preceding embodiments, the isolated CD45 + The cell population was approximately 2.0 x 10 3 More than 3.0 x 10 iNKT 3 More than 4.0 x 10 iNKT 3 More than 5.0 x 10 iNKT 3 More than 6.0 x 10 iNKT 3 More than 7.0 x 10 iNKT 3 More than 8.0 x 10 iNKT 3 More than 9.0 x 10 iNKT 3 More than 1.0 x 10 iNKT 4 More than 2.0 x 10 iNKT 4 More than 3.0 x 10 iNKT 4More than 4.0 x 10 iNKT 4 More than 5.0 x 10 iNKT 4 More than 6.0 x 10 iNKT 4 More than 7.0 x 10 iNKT 4 More than 8.0 x 10 iNKT 4 More than 9.0 x 10 iNKT 4 More than 1.0 x 10 iNKT 5 More than 2.0 x 10 iNKT 5 More than 3.0 x 10 iNKT 5 More than 4.0 x 10 iNKT 5 More than 5.0 x 10 iNKT 5 More than 6.0 x 10 iNKT 5 More than 7.0 x 10 iNKT 5 More than 8.0 x 10 iNKT 5 More than 9.0 x 10 iNKT 5 More than 1.0 x 10 iNKT 6 More than 1.5 x 10 iNKT 6 More than 2.0 x 10 iNKT 6 More than 2.5 x 10 iNKT 6 More than 3.0 x 10 iNKT 6 More than 3.5 x 10 iNKT 6 More than 4.0 x 10 iNKT 6 More than 4.5 x 10 iNKT 6 More than 5.0 x 10 iNKT 6 More than 5.5 x 10 iNKT 6 More than 6.0 x 10 iNKT 6 More than 6.5 x 10 iNKT 6 More than 7.0 x 10 iNKT 6 More than 7.5 x 10 iNKT 6 More than 8.0 x 10 iNKT 6 More than 8.5 x 10 iNKT 6 More than 9.0 x 10 iNKT 6 More than 9.5 x 10 iNKT 6 More than 1.0 x 10 iNKT 7More than 1.5 x 10 iNKT 7 More than 2.0 x 10 iNKT 7 More than 2.5 x 10 iNKT 7 More than 3.0 x 10 iNKT 7 More than 3.5 x 10 iNKT 7 More than 4.0 x 10 iNKT 7 More than 4.5 x 10 iNKT 7 More than 5.0 x 10 iNKT 7 More than 5.5 x 10 iNKT 7 More than 6.0 x 10 iNKT 7 More than 6.5 x 10 iNKT 7 More than 7.0 x 10 iNKT 7 More than 7.5 x 10 iNKT 7 More than 8.0 x 10 iNKT 7 More than 8.5 x 10 iNKT 7 More than 9.0 x 10 iNKT 7 More than 9.5 x 10 iNKT 7 More than 1.0 x 10 iNKT 8 More than 1.5 x 10 iNKT 8 More than 2.0 x 10 iNKT 8 More than 2.5 x 10 iNKT 8 More than 3.0 x 10 iNKT 8 More than 3.5 x 10 iNKT 8 10 or more iNKTs, or approximately 4.0 x 10 8 In some embodiments that may be combined with any of the preceding embodiments, the isolated CD45 + In some embodiments that may be combined with any of the preceding embodiments, the HSPCs are derived from an allogeneic donor that has at least one HLA mismatch relative to the human subject. + , CD133 + , CD90 + , CD38 - , CD45RA - , Lin - , CD19 - , TCRα -In some embodiments that may be combined with any of the preceding embodiments, Tmem is CD3 + CD45RO + In some embodiments that may be combined with any of the preceding embodiments, Tmem is a T central memory cell (T CM ) population, T effector memory cells (T EM ) population, T stem center memory cells (T SCM ), or any combination thereof. In some embodiments that may be combined with any of the preceding embodiments, T CM is CD4 + CD45RO + or CD8 + CD45RO + In some embodiments that may be combined with any of the preceding embodiments, T CM is CD45RA - , CD62L + , CCR7 + In some embodiments that may be combined with any of the preceding embodiments, T EM is CD4 + , CD45RO + , CD45RA - , CD62L - , CCR7 - In some embodiments that may be combined with any of the preceding embodiments, T SCM is CD4 + CD45RA + or CD8 + CD45RA + In some embodiments that may be combined with any of the preceding embodiments, T SCM CD95 + , CD122 + , CXCR3 + , LFA-1 + In some embodiments that may be combined with any of the preceding embodiments, Tregs are FOXP3 +In some embodiments that may be combined with any of the preceding embodiments, the Tregs comprise a population of naive Treg cells, a population of memory Treg cells, or a population of naive and memory Treg cells. In some embodiments that may be combined with any of the preceding embodiments, the naive Treg cells comprise CD4 + CD25 + CD127 dim FoxP3 + CD45RA + CD45RO - In some embodiments that may be combined with any of the preceding embodiments, Tregs are about 2.0 x 10 per kilogram of body weight of the human subject receiving the product. 5 ~Approx. 5.0×10 8 naive Treg cells, or approximately 8.0 x 10 5 ~Approx. 1.0×10 11 In some embodiments that may be combined with any of the preceding embodiments, the memory Treg cells comprise CD4 + CD25 + CD127 dim FoxP3 + CD45RA - CD45RO + In some embodiments that may be combined with any of the preceding embodiments, Tregs are about 5.0 x 10 per kilogram of body weight of the human subject receiving the product. 4 ~Approx. 5.0×10 8 memory Treg cells, or approximately 2.0 x 10 5 ~Approx. 1.0×10 11 In some embodiments that may be combined with any of the preceding embodiments, the Tcon comprises TCRα + , TCRβ + , or TCRα + TCRβ + In some embodiments that may be combined with any of the preceding embodiments, Tcon is CD25 - , CD127 + , or CD25 - CD127 +In some embodiments that may be combined with any of the preceding embodiments, Tcon is TCRα + TCRβ + CD45RA + CD45RO - CD25 - CD95 - IL-2Rβ - CD127 + In some embodiments that may be combined with any of the preceding embodiments, the iNKT is CD1d-tet + , 6B11 + , or CD1d-tet + 6B11 + In some embodiments that may be combined with any of the preceding embodiments, isolated CD45 + The population of cells contains less than about 5 EU to about 0.5 EU endotoxin per mL of formulation.

[0043] In some embodiments that may be combined with any of the preceding embodiments, the HSPCs, Tmems, Tregs, or any combination thereof are obtained from an allogeneic donor that is HLA-matched relative to the human subject receiving the product. In some embodiments that may be combined with any of the preceding embodiments, the isolated CD45 + The population of cells is derived from an allogeneic donor that is HLA-matched relative to the human subject receiving the product. In some embodiments that may be combined with any of the preceding embodiments, the HSPCs, Tmems, Tregs, or any combination thereof are obtained from an allogeneic donor that has at least one HLA mismatch relative to the human subject receiving the product. In some embodiments that may be combined with any of the preceding embodiments, the isolated CD45 +The population of cells is derived from an allogeneic donor with at least one HLA mismatch relative to the human subject receiving the product. In some embodiments that may be combined with any of the preceding embodiments, the at least one HLA mismatch is present in an allele selected from HLA-A, HLA-B, HLA-C, HLA-DRB1, and any combination thereof. In some embodiments that may be combined with any of the preceding embodiments, the cells with at least one HLA mismatch are derived from a donor that is 6 / 8 HLA mismatched relative to the human subject receiving the product, or a donor that is 7 / 8 HLA mismatched relative to the human subject receiving the product. In some embodiments that may be combined with any of the preceding embodiments, the donor that is 7 / 8 HLA mismatched relative to the human subject receiving the product has a mismatch in HLA-A. In some embodiments that may be combined with any of the preceding embodiments, the donor that is 7 / 8 HLA mismatched relative to the human subject receiving the product has a mismatch in HLA-B. In some embodiments that may be combined with any of the preceding embodiments, the donor who is 7 / 8 HLA mismatched relative to the human subject receiving the product has a mismatch in HLA-C. In some embodiments that may be combined with any of the preceding embodiments, the donor who is 7 / 8 HLA mismatched relative to the human subject receiving the product has a mismatch in HLA-DRB1. In some embodiments that may be combined with any of the preceding embodiments, the donor who has at least one HLA mismatch relative to the human subject receiving the product has a mismatched HLA allele because the donor is homozygous for the HLA allele but the human subject receiving the product is heterozygous for the HLA allele. In some embodiments that may be combined with any of the preceding embodiments, the donor who has at least one HLA mismatch relative to the human subject receiving the product has a mismatched HLA allele because the donor is heterozygous for the HLA allele but the human subject receiving the product is homozygous for the HLA allele.In some embodiments that may be combined with any of the preceding embodiments, the donor has at least one HLA mismatch compared to the human subject receiving the product, because both the donor and the human subject receiving the product are heterozygous for the HLA allele, and therefore the donor has a mismatched HLA allele. In some embodiments that may be combined with any of the preceding embodiments, the HSPCs, Tmems, Tregs, or any combination thereof are obtained from a half-matched allogeneic donor compared to the human subject receiving the product. In some embodiments that may be combined with any of the preceding embodiments, the isolated CD45. + The population of cells is derived from an allogeneic donor that is half-matched relative to the human subject receiving the product. In some embodiments that may be combined with any of the preceding embodiments, the allogeneic donor is related to the human subject receiving the product. In some embodiments that may be combined with any of the preceding embodiments, the allogeneic donor is unrelated to the human subject receiving the product.

[0044] In some embodiments that may be combined with any of the preceding embodiments, the method further includes collecting one or more mobilized peripheral blood donations from the donor. In some embodiments that may be combined with any of the preceding embodiments, the peripheral blood donations are mobilized with granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), plerixafor, or any combination thereof. In some embodiments that may be combined with any of the preceding embodiments, at least one of the mobilized peripheral blood donations is processed and selected using one or more immunoseparation particles (ISPs) to enrich for HSPCs, Tmems, and Tregs. In some embodiments that may be combined with any of the preceding embodiments, the one or more ISPs include an affinity reagent. In some embodiments that may be combined with any of the preceding embodiments, the affinity reagent is an immunomagnetic separation particle. In some embodiments that may be combined with any of the preceding embodiments, the immunomagnetic separation particles are antibodies each bound to an iron-containing particle. In some embodiments that may be combined with any of the preceding embodiments, the affinity reagent comprises a plurality of CD34 reagents that bind to CD34 on HSPCs. + The average number of ISPs per HSPC in the population of cells is about 20,000 or less. + The average number of ISPs per HSPC in the population of cells is about 1,000 to about 20,000. In some embodiments that may be combined with any of the preceding embodiments, the affinity reagent comprises a plurality of CD45RA reagents that bind to one or more CD45 receptors on Tmems. In some embodiments that may be combined with any of the preceding embodiments, the affinity reagent comprises a plurality of CD25 reagents that bind to one or more CD25 receptors on Tregs. In some embodiments that may be combined with any of the preceding embodiments, the isolated CD45 +The average number of ISPs per Treg in the population of cells is about 4000 or less. In some embodiments that may be combined with any of the preceding embodiments, the isolated CD45 +The average number of ISPs per Treg in the population of cells is about 1500 to about 2500. In some embodiments that may be combined with any of the preceding embodiments, the method further comprises administering a conditioning treatment prior to administration of the cell therapy product. In some embodiments that may be combined with any of the preceding embodiments, the conditioning treatment occurs about two days to about ten days before administration of the multicomponent cell therapy. In some embodiments that may be combined with any of the preceding embodiments, the conditioning treatment is a total body irradiation-based (TBI-based) regimen or a total body lymphatic irradiation-based (TLI-based) regimen. In some embodiments that may be combined with any of the preceding embodiments, the TBI-based regimen comprises fractionated total body irradiation. In some embodiments that may be combined with any of the preceding embodiments, the fractionated total body irradiation comprises two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, ten or more, eleven or more, twelve or more, thirteen or more, fourteen or more, or fifteen or more doses. In some embodiments that may be combined with any of the preceding embodiments, the fractionated total body irradiation comprises a total dose ranging from about 500 to about 1600 cGy. In some embodiments that may be combined with any of the preceding embodiments, the TBI-based regimen further comprises one or more transplant conditioning reagents. In some embodiments that may be combined with any of the preceding embodiments, the one or more transplant conditioning reagents are selected from cyclophosphamide, etoposide, fludarabine, thiotepa, antithymocyte globulin (ATG), and any combination thereof. In some embodiments that may be combined with any of the preceding embodiments, the transplant conditioning treatment is a myeloablative transplant conditioning treatment. In some embodiments that may be combined with any of the preceding embodiments, the myeloablative transplant conditioning treatment comprises one or more transplant conditioning reagents. In some embodiments that may be combined with any of the preceding embodiments, the one or more transplant conditioning reagents are selected from thiotepa, busulfan, melphalan, fludarabine, cyclophosphamide, antithymocyte globulin (ATG), and any combination thereof.In some embodiments that may be combined with any of the preceding embodiments, the myeloablative conditioning regimen includes three or more conditioning reagents, and at least one conditioning reagent includes thiotepa. In some embodiments that may be combined with any of the preceding embodiments, the myeloablative conditioning regimen includes one or more doses of busulfan, fludarabine, and thiotepa. In some embodiments that may be combined with any of the preceding embodiments, the one or more doses of busulfan, fludarabine, and thiotepa include about 5 to about 12 mg of thiotepa per kilogram of body weight of the human subject, about 7 to about 11 mg of busulfan per kilogram of body weight of the human subject, and about 100 to about 200 mg of fludarabine per square meter of body surface area, respectively.

[0045] In some embodiments that may be combined with any of the preceding embodiments, the overall survival rate for 12 months or more after administration of the cell therapy product ranges from about 75% to about 100%. In some embodiments that may be combined with any of the preceding embodiments, the overall survival of the human subject is increased after administration of the cell therapy product compared to a corresponding human subject undergoing standard myeloablative allogeneic hematopoietic stem cell transplant (allo-HSCT). In some embodiments that may be combined with any of the preceding embodiments, the GVHD- and relapse-free survival (GFRS) rate for 12 months or more after administration of the cell therapy product ranges from about 65% to about 100%. In some embodiments that may be combined with any of the preceding embodiments, the GVHD- and relapse-free survival (GFRS) rate for the human subject is increased after administration of the cell therapy product compared to a corresponding human subject undergoing standard myeloablative allogeneic hematopoietic stem cell transplant (allo-HSCT). In some embodiments that may be combined with any of the preceding embodiments, the relapse-free survival rate for 12 months or more after administration of the cell therapy product ranges from about 70% to about 100%. In some embodiments that may be combined with any of the preceding embodiments, relapse-free survival of a human subject is increased after administration of the cell therapy product compared to a corresponding human subject who underwent standard myeloablative allogeneic hematopoietic stem cell transplant (alloHSCT). In some embodiments that may be combined with any of the preceding embodiments, the incidence of acute GVHD for 100 days or more after administration of the cell therapy product ranges from about 9% to about 31%. In some embodiments that may be combined with any of the preceding embodiments, the incidence of chronic GVHD for 100 days or more after administration of the cell therapy product ranges from about 1% to about 10%. In some embodiments that may be combined with any of the preceding embodiments, the incidence of post-transplant lymphoproliferative disorder (PTLD) for 100 days or more after administration of the cell therapy product ranges from about 1% to about 10%. In some embodiments that may be combined with any of the preceding embodiments, the incidence of Grade 2 or higher infections for 100 days or more after administration of the cell therapy product ranges from about 23% to about 31%.

[0046] Another aspect of the present disclosure relates to a method of treating a human subject having or suspected of having multiple sclerosis, the method comprising administering an isolated CD45+ administering to a human subject a cell therapy product comprising a population of isolated CD45 cells. + The cell population is CD34 + Enriched population of hematopoietic stem and progenitor cells (HSPCs), CD45RA - Enriched populations of memory T cells (Tmem), and fresh CD4 + CD25 + CD127 dim Contains an enriched population of regulatory T cells (Tregs), isolated CD45 + The population of cells is approximately 5.0 x 10 per kilogram of body weight of the human subject receiving the product. 5 < naive conventional CD3 + CD25 - CD45RA + T cells (Tcon), approximately 6.0×10 7 < 100 total naive conventional CD3 + CD25 - CD45RA + T cells (Tcon), or approximately 1.0 × 10 6 < 100 total naive conventional CD3 + CD25 - CD45RA + Naive conventional CD3 to contain T cells (Tcon) + CD25 - CD45RA + T cells (Tcon) are depleted. Another aspect of the present disclosure relates to a method for treating a human subject having or suspected of having multiple sclerosis, the method comprising administering to the human subject a cell therapy product of the present disclosure. In some embodiments, the multiple sclerosis is primary progressive multiple sclerosis. In some embodiments, the multiple sclerosis is chronic progressive multiple sclerosis. In some embodiments, the multiple sclerosis is secondary progressive multiple sclerosis. In some embodiments, the multiple sclerosis is relapsing-remitting multiple sclerosis. In some embodiments, the multiple sclerosis is acute-remitting multiple sclerosis.

[0047] In some embodiments that may be combined with any of the preceding embodiments, the human subject is about 3 months of age or older. In some embodiments that may be combined with any of the preceding embodiments, the human subject is about 3 months to about 18 years of age. In some embodiments that may be combined with any of the preceding embodiments, the human subject is about 12 years of age or older. In some embodiments that may be combined with any of the preceding embodiments, the human subject is about 12 years of age to about 65 years of age. In some embodiments that may be combined with any of the preceding embodiments, the human subject is about 12 years of age to about 75 years of age. In some embodiments that may be combined with any of the preceding embodiments, the human subject is about 65 years of age to about 75 years of age. In some embodiments that may be combined with any of the preceding embodiments, the human subject is about 3 months of age to about 75 years of age. In some embodiments that may be combined with any of the preceding embodiments, the human subject has previously received one to five lines of therapy.

[0048] Another aspect of the present disclosure relates to a cell therapy kit comprising the cell therapy product of the present disclosure. Another aspect of the present disclosure relates to an isolated CD45 + and a cell therapy kit comprising a population of cells, wherein the population comprises isolated CD45 + The population of cells is a) approximately 1.0 x 10 per kilogram of body weight of the human subject receiving the product 5 ~Approx. 1.0×10 8 CD34 + A dose of hematopoietic stem and progenitor cells (HSPCs), or approximately 5.0 × 10 5 ~Approx. 1.5×10 10 CD34 + a total dose of hematopoietic stem and progenitor cells (HSPCs), b) approximately 1.0 × 10 per kilogram of body weight of the human subject receiving the product 5 ~Approx. 1.0×10 8 CD45RA - A dose of memory T cells (Tmem), or approximately 5.0 × 10 5 ~Approx. 1.5×10 10 CD45RA - and c) approximately 1.0 x 10 total dose of memory T cells (Tmem) per kilogram of body weight of the human subject receiving the product. 5 ~Approx. 2.0×107 fresh CD4 + CD25 + CD127 dim Regulatory T cell (Treg) dose, or approximately 5.0 × 10 5 ~Approx. 3.0×10 9 Pieces of isolated fresh + CD4 + CD25 + CD127 dim Contains a total dose of regulatory T cells (Tregs) and isolated CD45 + The population of cells is approximately 5.0 x 10 per kilogram of body weight of the human subject receiving the product. 5 < naive conventional CD3 + CD25 - CD45RA + T cells (Tcon), approximately 6.0×10 7 < 100 total naive conventional CD3 + CD25 - CD45RA + T cells (Tcon), or approximately 1.0 × 10 6 < 100 total naive conventional CD3 + CD25 - CD45RA + Naive conventional CD3 to contain T cells (Tcon) + CD25 - CD45RA + T cell (Tcon) depleted and isolated CD45 + The population of cells is formulated with an excipient at a neutral pH. Another aspect of the present disclosure is an isolated CD45 + and a cell therapy kit comprising a container containing a population of cells, the container comprising an isolated CD45 + The population of cells is a) approximately 1.0 x 10 per kilogram of body weight of the human subject receiving the product 5 ~Approx. 1.0×10 8 CD34 + A dose of hematopoietic stem and progenitor cells (HSPCs), or approximately 5.0 × 10 5 ~Approx. 1.5×10 10 CD34 + a total dose of hematopoietic stem and progenitor cells (HSPCs), b) approximately 1.0 × 10 per kilogram of body weight of the human subject receiving the product5 ~Approx. 1.0×10 8 A dose of CD45RA memory T cells (Tmem), or approximately 5.0 x 10 5 ~Approx. 1.5×10 10 and c) a total dose of approximately 1.0 x 10 CD45RA memory T cells (Tmem) per kilogram of body weight of the human subject receiving the product. 5 ~Approx. 2.0×10 7 fresh CD4 + CD25 + CD127 dim Regulatory T cell (Treg) dose, or approximately 5.0 × 10 5 ~Approx. 3.0×10 9 Pieces of isolated fresh + CD4 + CD25 + CD127 dim Contains a total dose of regulatory T cells (Tregs) and isolated CD45 + The population of cells is approximately 5.0 x 10 per kilogram of body weight of the human subject receiving the product. 5 < naive conventional CD3 + CD25 - CD45RA + T cells (Tcon), approximately 6.0×10 7 < 100 total naive conventional CD3 + CD25 - CD45RA + T cells (Tcon), or approximately 1.0 × 10 6 < 100 total naive conventional CD3 + CD25 - CD45RA + Naive conventional CD3 to contain T cells (Tcon) + CD25 - CD45RA + T cell (Tcon) depleted and isolated CD45 +The population of cells is formulated with an excipient at a neutral pH. In some embodiments that may be combined with any of the preceding embodiments, the kit further includes written instructions for using the cell therapy to treat a malignant hematological disease in a human subject. In some embodiments that may be combined with any of the preceding embodiments, the malignant hematological disease is selected from leukemia, acute leukemia, acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), mixed phenotype acute leukemia (MPAL), chronic myeloid leukemia (CML), multiple myeloma, lymphoma, Hodgkin's lymphoma, non-Hodgkin's lymphoma, myelodysplastic syndrome (MDS), myeloproliferative syndrome, myelofibrosis, and blastic plasmacytoid dendritic cell neoplasm (BPDCN). In some embodiments that may be combined with any of the preceding embodiments, the kit further includes written instructions for using the cell therapy to treat multiple sclerosis in a human subject.

[0049] Another aspect of the present disclosure relates to a unit dose comprising the cell therapy product of the present disclosure. Another aspect of the present disclosure relates to an isolated CD45 + For a unit dose containing a population of cells, isolated CD45 + The population of cells is a) approximately 1.0 x 10 per kilogram of body weight of the human subject receiving the product 5 ~Approx. 1.0×10 8 CD34 + Hematopoietic stem and progenitor cells (HSPCs), or approximately 5.0 × 10 5 ~Approx. 1.5×10 10 CD34 + a total dose of hematopoietic stem and progenitor cells (HSPCs), b) approximately 1.0 × 10 per kilogram of body weight of the human subject receiving the product 5 ~Approx. 1.0×10 8 CD45RA - The dose of memory T cells (Tmem), or approximately 5.0 × 10 5 ~Approx. 1.5×10 10 CD45RA - and / or c) about 1.0 x 10 total dose of memory T cells (Tmem) per kilogram of body weight of the human subject receiving the product. 5 ~Approx. 2.0×10 7fresh CD4 + CD25 + CD127 dim The dose of regulatory T cells (Tregs), or approximately 5.0 × 10 5 ~Approx. 3.0×10 9 Pieces of isolated fresh + CD4 + CD25 + CD127 dim Contains a total dose of regulatory T cells (Tregs) and isolated CD45 + The population of cells is approximately 5.0 x 10 per kilogram of body weight of the human subject receiving the product. 5 < naive conventional CD3 + CD25 - CD45RA + T cells (Tcon), approximately 6.0×10 7 < 100 total naive conventional CD3 + CD25 - CD45RA + T cells (Tcon), or approximately 1.0 × 10 6 < 100 total naive conventional CD3 + CD25 - CD45RA + Naive conventional CD3 to contain T cells (Tcon) + CD25 - CD45RA + In some embodiments, isolated CD45 T cells (Tcon) are depleted. + The population of cells further comprises one or more excipients. Other embodiments of the present disclosure include: a) a concentration of about 1.0 x 10 cells per kilogram of body weight of the human subject receiving the product; 5 ~Approx. 1.0×10 8 CD34 + Hematopoietic stem and progenitor cells (HSPCs), or approximately 5.0 × 10 5 ~Approx. 1.5×10 10 CD34 + a total dose of hematopoietic stem and progenitor cells (HSPCs), and one or more excipients; b) approximately 1.0 x 10 per kilogram of body weight of a human subject receiving the product. 5 ~Approx. 1.0×10 8 CD45RA memory T cells (Tmem), or approximately 5.0 × 10 5~Approx. 1.5×10 10 CD45RA - a total dose of memory T cells (Tmem), and one or more excipients, and c) about 1.0 x 10 per kilogram of body weight of a human subject receiving the product. 5 ~Approx. 2.0×10 7 fresh CD4 + CD25 + CD127 dim Regulatory T cells (Tregs), or approximately 5.0 × 10 5 ~Approx. 3.0×10 9 Pieces of isolated fresh + CD4 + CD25 + CD127 dim For a unit dose containing a total dose of regulatory T cells (Tregs), as well as one or more excipients, the unit dose is about 5.0 x 10 per kilogram of body weight of the human subject receiving the product. 5 < naive conventional CD3 + CD25 - CD45RA + T cells (Tcon), approximately 6.0×10 7 < 100 total naive conventional CD3 + CD25 - CD45RA + T cells (Tcon), or approximately 1.0 × 10 6 < 100 total naive conventional CD3 + CD25 - CD45RA + Naive conventional CD3 to contain T cells (Tcon) + CD25 - CD45RA + T cells (Tcon) are depleted.

[0050] Another aspect of the present disclosure relates to an article of manufacture comprising the cell therapy product of the present disclosure. Another aspect of the present disclosure relates to an isolated CD45 + For articles of manufacture containing a population of cells, isolated CD45 + The population of cells is a) approximately 1.0 x 10 per kilogram of body weight of the human subject receiving the product 5 ~Approx. 1.0×10 8 CD34 +A dose of hematopoietic stem and progenitor cells (HSPCs), or approximately 5.0 × 10 5 ~Approx. 1.5×10 10 CD34 + a total dose of hematopoietic stem and progenitor cells (HSPCs), b) approximately 1.0 × 10 per kilogram of body weight of the human subject receiving the product 5 ~Approx. 1.0×10 8 CD45RA - A dose of memory T cells (Tmem), or approximately 5.0 × 10 5 ~Approx. 1.5×10 10 CD45RA - and c) approximately 1.0 x 10 total dose of memory T cells (Tmem) per kilogram of body weight of the human subject receiving the product. 5 ~Approx. 2.0×10 7 fresh CD4 + CD25 + CD127 dim Regulatory T cell (Treg) dose, or approximately 5.0 × 10 5 ~Approx. 3.0×10 9 Pieces of isolated fresh + CD4 + CD25 + CD127 dim Contains a total dose of regulatory T cells (Tregs) and isolated CD45 + The population of cells is approximately 5.0 x 10 per kilogram of body weight of the human subject receiving the product. 5 < naive conventional CD3 + CD25 - CD45RA + T cells (Tcon), approximately 6.0×10 7 < 100 total naive conventional CD3 + CD25 - CD45RA + T cells (Tcon), or approximately 1.0 × 10 6 < 100 total naive conventional CD3 + CD25 - CD45RA + Naive conventional CD3 to contain T cells (Tcon) + CD25 - CD45RA + T cell (Tcon) depleted and isolated CD45+ The population of cells is formulated with an excipient at a neutral pH. Another aspect of the present disclosure is an isolated CD45 + an article of manufacture comprising a container containing a population of cells, said article comprising an isolated CD45 + The population of cells is a) approximately 1.0 x 10 per kilogram of body weight of the human subject receiving the product 5 ~Approx. 1.0×10 8 CD34 + A dose of hematopoietic stem and progenitor cells (HSPCs), or approximately 5.0 × 10 5 ~Approx. 1.5×10 10 CD34 + a total dose of hematopoietic stem and progenitor cells (HSPCs), b) approximately 1.0 × 10 per kilogram of body weight of the human subject receiving the product 5 ~Approx. 1.0×10 8 A dose of CD45RA memory T cells (Tmem), or approximately 5.0 x 10 5 ~Approx. 1.5×10 10 and c) a total dose of approximately 1.0 x 10 CD45RA memory T cells (Tmem) per kilogram of body weight of the human subject receiving the product. 5 ~Approx. 2.0×10 7 fresh CD4 + CD25 + CD127 dim Regulatory T cell (Treg) dose, or approximately 5.0 × 10 5 ~Approx. 3.0×10 9 Pieces of isolated fresh + CD4 + CD25 + CD127 dim Contains a total dose of regulatory T cells (Tregs) and isolated CD45 + The population of cells is approximately 5.0 x 10 per kilogram of body weight of the human subject receiving the product. 5 < naive conventional CD3 + CD25 - CD45RA + T cells (Tcon), approximately 6.0×10 7 < 100 total naive conventional CD3 + CD25 - CD45RA + T cells (Tcon), or approximately 1.0 × 106 < 100 total naive conventional CD3 + CD25 - CD45RA + Naive conventional CD3 to contain T cells (Tcon) + CD25 - CD45RA + T cell (Tcon) depleted and isolated CD45 + The population of cells is formulated with an excipient at a neutral pH. In some embodiments that may be combined with any of the preceding embodiments, the article of manufacture further comprises instructions for administering the article of manufacture to a human subject to treat a malignant hematological disease. In some embodiments that may be combined with any of the preceding embodiments, the malignant hematological disease is selected from leukemia, acute leukemia, acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), mixed phenotype acute leukemia (MPAL), chronic myeloid leukemia (CML), multiple myeloma, lymphoma, Hodgkin's lymphoma, non-Hodgkin's lymphoma, myelodysplastic syndrome (MDS), myeloproliferative syndrome, myelofibrosis, and blastic plasmacytoid dendritic cell neoplasm (BPDCN). In some embodiments that may be combined with any of the preceding embodiments, the article of manufacture further comprises instructions for administering the article of manufacture to a human subject to treat multiple sclerosis.

[0051] Another aspect of the present disclosure relates to a container containing the cell therapy product of the present disclosure. Another aspect of the present disclosure relates to an isolated CD45 + a vessel containing a population of cells, the vessel containing the isolated CD45 + The population of cells is a) approximately 1.0 x 10 per kilogram of body weight of the human subject receiving the product 5 ~Approx. 1.0×10 8 CD34 + A dose of hematopoietic stem and progenitor cells (HSPCs), or approximately 5.0 × 10 5 ~Approx. 1.5×10 10 CD34 + a total dose of hematopoietic stem and progenitor cells (HSPCs), b) approximately 1.0 × 10 per kilogram of body weight of the human subject receiving the product 5 ~Approx. 1.0×10 8A dose of CD45RA memory T cells (Tmem), or approximately 5.0 x 10 5 ~Approx. 1.5×10 10 and c) a total dose of approximately 1.0 x 10 CD45RA memory T cells (Tmem) per kilogram of body weight of the human subject receiving the product. 5 ~Approx. 2.0×10 7 fresh CD4 + CD25 + CD127 dim Regulatory T cell (Treg) dose, or approximately 5.0 × 10 5 ~Approx. 3.0×10 9 Pieces of isolated fresh + CD4 + CD25 + CD127 dim Contains a total dose of regulatory T cells (Tregs) and isolated CD45 + The population of cells is approximately 5.0 x 10 per kilogram of body weight of the human subject receiving the product. 5 < naive conventional CD3 + CD25 - CD45RA + T cells (Tcon), approximately 6.0×10 7 < 100 total naive conventional CD3 + CD25 - CD45RA + T cells (Tcon), or approximately 1.0 × 10 6 < 100 total naive conventional CD3 + CD25 - CD45RA + Naive conventional CD3 to contain T cells (Tcon) + CD25 - CD45RA + T cell (Tcon) depleted and isolated CD45 + The population of cells is formulated with excipients at a neutral pH. Other aspects of the present disclosure include: a) a concentration of about 1.0 x 10 cells per kilogram of body weight of a human subject receiving the product; 5 ~Approx. 1.0×10 8 CD34 + Hematopoietic stem and progenitor cells (HSPCs), or approximately 5.0 × 10 5 ~Approx. 1.5×10 10 CD34+ a total dose of hematopoietic stem and progenitor cells (HSPCs), and one or more excipients; b) approximately 1.0 x 10 per kilogram of body weight of a human subject receiving the product. 5 ~Approx. 1.0×10 8 CD45RA memory T cells (Tmem), or approximately 5.0 × 10 5 ~Approx. 1.5×10 10 CD45RA - a total dose of memory T cells (Tmem), and one or more excipients, and c) about 1.0 x 10 per kilogram of body weight of a human subject receiving the product. 5 ~Approx. 2.0×10 7 fresh CD4 + CD25 + CD127 dim Regulatory T cells (Tregs), or approximately 5.0 × 10 5 ~Approx. 3.0×10 9 Pieces of isolated fresh + CD4 + CD25 + CD127 dim For a container containing a total dose of regulatory T cells (Tregs) and one or more excipients, the HSPCs, Tmems, and / or Tregs are about 5.0 x 10 per kilogram of body weight of a human subject receiving the product. 5 < naive conventional CD3 + CD25 - CD45RA + T cells (Tcon), approximately 6.0×10 7 < 100 total naive conventional CD3 + CD25 - CD45RA + T cells (Tcon), or approximately 1.0 × 10 6 < 100 total naive conventional CD3 + CD25 - CD45RA + Naive conventional CD3 to contain T cells (Tcon) + CD25 - CD45RA + T cells (Tcon) are depleted. [Brief explanation of the drawings]

[0052] The novel features of the present disclosure are set forth with particularity in the appended claims. A better understanding of the features and advantages of the present disclosure will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the disclosure are utilized, and the accompanying drawings.

[0053] [Figure 1] FIG. 1 shows a schematic diagram of implant creation and administration. [Figure 2] Figures 2A-C show neutrophil and platelet engraftment in the test cohort. [Figure 3] Figures 3A-C show the incidence of grade 2-4 aGVHD in the study cohorts (e.g., group A, MRD / MUD and MMUD, group B, haplo, and group C, no GVHD prophylaxis). [Figure 4] Figures 4A-C show the incidence of grade 2-4 aGVHD in the study cohort receiving >1 x 106 Tmems per kg ABW or (adjusted) IBW of recipient subjects. [Figure 5] Figures 5A-C show the incidence of grade 3-4 aGVHD in different cohorts of the study. [Figure 6] Figures 6A-C show the incidence of all grades of chronic GVHD in the study cohort. [Figure 7] Figures 7A-C show the incidence of disease recurrence in the different cohorts of the study. [Figure 8] Figures 8A-C show the incidence of NRM in different cohorts of the study. [Figure 9] Figures 9A-C show OS in different cohorts of the study. [Figure 10] Figures 10A-C show the RFS in different cohorts of the study. [Figure 11] Figures 11A-C show the GRFS in different cohorts of the study. [Figure 12] Figures 12A-D show the incidence of all infections in the various arms of the study at approximately one year post-transplant. [Figure 13]Figures 13A-C show the incidence of all infections in the various cohorts of the study at approximately one year post-transplant. [Figure 14] Figures 14A-B show the incidence of infection in the various groups of the study at approximately 1000 days post-transplant. [Figure 15] Figure 15 compares the recurrence rate and study design of this study with those of Gooptu (Blood 2021) and Wagner (Blood Advances 2021). [Figure 16] FIG. 16 shows GVHD and relapse-free survival in haploidentical transplants. [Figure 17] FIG. 17 shows overall survival (OS) by combined Tmem dose. [Figure 18] FIG. 18 shows overall survival (OS) by study arm with a combined Tmem dose of ≧10×10 6 cells / kg. [Figure 19] FIG. 19 shows GVHD and relapse-free survival (GRFS) by combined Tmem dose. [Figure 20] FIG. 20 shows GVHD and relapse-free survival (GRFS) by study arm with a combined Tmem dose of ≧10×10 6 cells / kg. [Figure 21] FIG. 21 shows relapse-free survival by combined Tmem dose. [Figure 22] FIG. 22 shows relapse-free survival by test group with combined Tmem doses of ≧10×10 6 cells / kg. [Figure 23] FIG. 23 shows GVHD and relapse-free survival (GRFS) in haploidentical transplants. DETAILED DESCRIPTION OF THE INVENTION

[0054] Detailed Description Introduction Various embodiments of the present disclosure provide compositions, drug treatments, cell populations, solutions, formulations, kits, and / or methods related to improving allogeneic hematopoietic stem cell transplantation (alloHCT).

[0055] Standard allogeneic hematopoietic stem and progenitor cells (HSPCs), usually derived from the donor's bone marrow, peripheral blood, or umbilical cord blood, are transplanted into a recipient. The recipient may undergo myeloablative conditioning, which kills hematopoietic cells, including tumor cells and host immune cells. The HSPCs transplanted into the recipient then reconstitute the hematopoietic compartment. HCT can be useful as a treatment for cancer due to the ability of donor T cells to exert an antitumor effect, termed graft-versus-tumor (GVT). In patients with hematologic malignancies refractory to chemotherapy, HCT is associated with improved survival.

[0056] Surprisingly, alloHCT recipients who received single-agent graft-versus-host disease (GVHD) prophylaxis, such as tacrolimus, had significantly better clinical outcomes than recipients who received existing alloHCT regimens and standard therapies. These recipients experienced improved clinical outcomes after single-agent GVHD prophylaxis consisting of tacrolimus, including increased overall survival, increased relapse-free survival, increased GVHD- and relapse-free survival (GRFS), more rapid and / or complete engraftment of various hematopoietic components (e.g., neutrophils, platelets, T cells, B cells), improved donor chimerism (e.g., T cell chimerism), reduced relapses, reduced primary engraftment failure, reduced secondary engraftment failure, reduced treatment-related mortality, reduced acute and / or chronic GVHD, and shorter time to hospital discharge.

[0057] Although alloHCT is associated with improved survival for patients with hematologic malignancies refractory to chemotherapy, some patients treated with existing alloHCT regimens experience cancer recurrence, and numerous complications can limit the effectiveness of standard alloHCT. The efficacy of standard alloHCT can be limited by, for example, primary engraftment failure, secondary engraftment failure, limited or delayed engraftment of various hematopoietic components (e.g., neutrophils, platelets, T cells, or B cells), and limited donor chimerism (e.g., T cell chimerism). Furthermore, standard alloHCT can result in treatment-related ethics or toxicity. However, donor T cells may also attack non-tumor host cells, resulting in graft-versus-host disease (GVHD). GVHD is a major cause of post-HCT complications and can be fatal. Managing GVHD may require immunosuppressive therapy or cytotoxic mediators, which can lead to toxicity, increased susceptibility to infection, and / or blunted antitumor immunity. Early morbidity and mortality associated with acute graft-versus-host disease (aGVHD; occurring within the first 100 days after transplantation) are major factors limiting the success of HCT, as is the long-term morbidity associated with chronic GVHD (cGVHD). GVHD is a risk for both HLA-matched and HLA-mismatched transplants. GVHD can occur even when the donor and recipient are HLA-matched because the immune system can still recognize other differences between the donor tissues.

[0058] Both GVT and GVHD initiate an immune response upon recognition of cognate antigens by T cell receptors, e.g., naive conventional CD3 + CD25 - CD45RA +GVHD is primarily mediated by conventional T cells, such as T cells (Tcon). Depleting T cells from hematopoietic stem cell transplant (HCT) grafts can reduce GVHD, but this can also result in reduced GVHD and increased likelihood of cancer recurrence. In addition to Tcon, Tregs are a further subset of T cells that negatively regulate inflammation and promote immune tolerance. Tregs can prevent or reduce GVHD by negatively regulating inflammation, including inflammation induced when donor Tcon recognizes recipient antigens.

[0059] Provided herein are compositions and methods for improved alloHCT, including administering to a subject a cell population comprising, for example, CD34+ cells (e.g., HSPCs), Tregs, and Tmems, wherein the population of cells is selected from naive conventional αβ-T cells or naive conventional CD3 + CD25 - CD45RA + T cells (Tcon) are depleted. Without wishing to be bound by theory, Tregs are an enriched cell population, and are depleted of naive conventional αβ-T cells or naive conventional CD3 + CD25 - CD45RA + Administering a population of T cell (Tcon)-depleted cells reduces the incidence and / or severity of GVHD and / or enhances GVT. Accordingly, embodiments of the present disclosure provide compositions, drug treatments, cell therapy products, cell populations, solutions, formulations, kits, and / or methods for enhancing GVT while minimizing GVHD. Thus, the compositions, drug treatments, cell therapy products, cell populations, solutions, formulations, kits, and / or methods disclosed herein can prevent or reduce graft-versus-host disease (GVHD) in a subject while preserving the graft-versus-tumor (GVT) effect of alloHCT administered to a subject with cancer (e.g., a hematological cancer). In some embodiments, one or more doses of the cell population are administered simultaneously or at different times.

[0060] Therapeutic agents for hematopoietic cell transplantation cell population Embodiments of the present disclosure provide a drug therapy or cell therapy product administered to a human subject in need thereof. In some embodiments, the therapy includes enriched populations of hematopoietic stem / progenitor cells (HSPCs), memory T cells (Tmem), regulatory T cells (Treg), and invariant natural killer T cells (iNKT), where the population of cells is enriched for specific conventional T cells (e.g., naive conventional αβ-T cells or naive conventional CD3 T cells). + CD25 - CD45RA + In some embodiments, the treatment or therapy may further comprise a solution that does not include or contains a dose of a graft-versus-host disease (GVHD) prophylactic agent (e.g., tacrolimus). In various embodiments, the HSPCs are depleted of CD34 + In some embodiments, the cell therapy product is an isolated CD45 + Isolated CD45 containing cell populations + The population of cells is a) approximately 1.0 x 10 per kilogram of body weight of the human subject receiving the product 5 ~Approx. 1.0×10 8 CD34 + A dose of hematopoietic stem and progenitor cells (HSPCs), or approximately 5.0 × 10 5 ~Approx. 1.5×10 10 CD34 + a total dose of hematopoietic stem and progenitor cells (HSPCs), b) approximately 1.0 × 10 per kilogram of body weight of the human subject receiving the product 5 ~Approx. 1.0×10 8 CD45RA - A dose of memory T cells (Tmem), or approximately 5.0 × 10 5 ~Approx. 1.5×10 10 CD45RA - and c) approximately 1.0 x 10 total dose of memory T cells (Tmem) per kilogram of body weight of the human subject receiving the product. 5 ~Approx. 2.0×10 7 fresh CD4 + CD25 + CD127 dim Regulatory T cell (Treg) dose, or approximately 5.0 × 10 5~Approx. 3.0×10 9 Pieces of isolated fresh + CD4 + CD25 + CD127 dim The cell therapy product contains a total dose of regulatory T cells (Tregs) of approximately 5.0 x 10 per kilogram of body weight of the human subject receiving the product. 5 < naive conventional CD3 + CD25 - CD45RA + T cells (Tcon), approximately 6.0×10 7 < 100 total naive conventional CD3 + CD25 - CD45RA + T cells (Tcon), or approximately 1.0 × 10 6 < 100 total naive conventional CD3 + CD25 - CD45RA + Naive conventional CD3 to contain T cells (Tcon) + CD25 - CD45RA + T cell (Tcon) depleted and isolated CD45 + The population of cells is formulated with an excipient at a neutral pH.

[0061] In certain embodiments, the present disclosure provides distinct therapeutic cell populations that form pharmaceutical compositions or cell therapy products useful for hematopoietic stem / progenitor cell transplantation. The therapeutic cell populations can include enriched populations of hematopoietic stem / progenitor cells (HSPCs), memory T cells (Tmem), regulatory T cells (Treg), and iNKT cells, and the populations of cells are depleted of naive conventional αβ-T cells and / or enriched for naive conventional CD3 T cells. + CD25 - CD45RA + T cells (Tcon) are depleted.

[0062] In some embodiments, the subject receiving drug therapy has undergone a myeloablative conditioning regimen that includes thiotepa.

[0063] In some embodiments, a particular therapeutic cell population comprising HSPCs, Tmem, and Tregs is obtained from a single donor. In some embodiments, the population of cells comprising HSPCs, Tmem, and Tregs is allogeneic compared to the human subject. In some embodiments, the population of cells comprising HSPCs, Tmem, and Tregs is obtained from a donor that is HLA-matched compared to the human subject. In some embodiments, the population of cells comprising HSPCs, Tmem, and Tregs is obtained from a donor that is HLA-mismatched compared to the human subject. In some embodiments, the population of cells comprising HSPCs, Tmem, and Tregs is obtained from a donor that is half-matched compared to the human subject. Provided herein are compositions, drug treatments, cell populations, solutions, formulations, kits, and / or methods for improving hematopoietic stem cell transplantation (HCT), for example, allogeneic hematopoietic stem cell transplantation (alloHCT). The compositions, drug treatments, cell populations, solutions, formulations, kits, and / or methods disclosed herein may include cell populations that can be administered in combination with GVHD prophylaxis to achieve positive clinical outcomes. The compositions, drug treatments, cell populations, solutions, formulations, kits, and / or methods disclosed herein may include cell populations that can be administered in conjunction with or alone as a GVHD prophylactic to achieve a positive clinical outcome. The cell populations may include one or more cell types, such as hematopoietic stem and progenitor cells (HSPCs), regulatory T cells (Tregs), invariant natural killer T cells (iNKTs), memory T cells (Tmems), and combinations thereof. The cell populations may be depleted of naive conventional αβ-T cells and / or naive conventional CD3 T cells. + CD25 - CD45RA + T cells (Tcon) can be depleted.

[0064] The present disclosure provides parameters related to cell populations and methods for administering cell populations, which may contribute to a favorable clinical outcome in HCT recipient subjects. Without wishing to be bound by theory, parameters that may contribute to a favorable clinical outcome in HCT recipient subjects include, for example, a conditioning treatment (e.g., a myeloablative conditioning treatment), administration of a GVHD preventative agent described herein (e.g., tacrolimus), the dose of administered cells, the timing of administration of cells, the purity criteria of cells, the method for obtaining cells, the method for handling or storing cells, and combinations thereof.

[0065] In some embodiments, CD34 + Hematopoietic stem and progenitor cells (HSPCs) can have extensive self-renewal capacity and the ability to differentiate into specialized cell types, e.g., to reconstitute all hematopoietic cell lineages. HSPCs can undergo asynchronous replication, in which two daughter cells are produced with distinct phenotypes. HSPCs can exist in a mitotically quiescent form. HSPCs can be derived from bone marrow, peripheral blood, and / or umbilical cord blood. In some embodiments, HSPCs are CD34 + HSPCs express CD133 + , CD90 + , CD38 - , CD45RA - , Lin - In some embodiments, the HSPCs may be further or alternatively described as CD19, - , TCRα / β - , or a combination thereof.

[0066] In some embodiments, the HSPCs are present in a composition, a cell therapy product, and / or are present in an amount of about 1.0 x 10 HSPCs per kilogram of body weight of a human subject. 5 ~Approx. 5.0×10 8 Approximately 1.0 x 10 HSPCs per kilogram of body weight in a human subject 5 ~Approx. 1.0×10 8 HSPCs, or approximately 5.0 x 10 per kilogram of body weight in a human subject5 ~Approx. 2.0×10 7 In some embodiments, the HSPCs are administered to a subject in an amount or dose that may comprise about 1.0 x 10 HSPCs per kilogram of body weight of a human subject. In some embodiments, the HSPCs are present in a composition, a cell therapy product, and / or are administered to a subject in an amount or dose that may comprise about 1.0 x 10 HSPCs per kilogram of body weight of a human subject. 5 ≥ 1.5 x 10 HSPCs per kilogram of body weight in a human subject 5 ≥ 2.0 x 10 HSPCs per kilogram of body weight in a human subject 5 ≥ 2.5 x 10 HSPCs per kilogram of body weight in a human subject 5 ≥ 3.0 x 10 HSPCs per kilogram of body weight in a human subject 5 ≥ 3.5 x 10 HSPCs per kilogram of body weight in a human subject 5 ≥ 4.0 x 10 HSPCs per kilogram of body weight in a human subject 5 ≥ 4.5 x 10 HSPCs per kilogram of body weight in a human subject 5 ≥ 5.0 x 10 HSPCs per kilogram of body weight in a human subject 5 ≥ 5.5 x 10 HSPCs per kilogram of body weight in a human subject 5 ≥ 6.0 x 10 HSPCs per kilogram of body weight in a human subject 5 ≥ 6.5 x 10 HSPCs per kilogram of body weight in a human subject 5 ≥ 7.0 x 10 HSPCs per kilogram of body weight in a human subject 5 ≥ 7.5 x 10 HSPCs per kilogram of body weight in a human subject 5 ≥ 8.0 x 10 HSPCs per kilogram of body weight in a human subject 5 ≥ 8.5 x 10 HSPCs per kilogram of body weight in a human subject 5 ≥ 9.0 x 10 HSPCs per kilogram of body weight in a human subject 5 ≥ 9.5 x 10 HSPCs per kilogram of body weight in a human subject 5 ≥ 1.0 x 10 HSPCs per kilogram of body weight in a human subject 6 ≥ 1.25 x 10 HSPCs per kilogram of body weight in a human subject 6≥ 1.5 x 10 HSPCs per kilogram of body weight in a human subject 6 ≥ 1.75 x 10 HSPCs per kilogram of body weight in a human subject 6 ≥ 2.0 x 10 HSPCs per kilogram of body weight in a human subject 6 ≥ 2.25 x 10 HSPCs per kilogram of body weight in a human subject 6 ≥ 2.5 x 10 HSPCs per kilogram of body weight in a human subject 6 ≥ 2.75 x 10 HSPCs per kilogram of body weight in a human subject 6 ≥ 3.0 x 10 HSPCs per kilogram of body weight in a human subject 6 ≥ 3.25 x 10 HSPCs per kilogram of body weight in a human subject 6 ≥ 3.5 x 10 HSPCs per kilogram of body weight in a human subject 6 ≥ 3.75 x 10 HSPCs per kilogram of body weight in a human subject 6 ≥ 4.0 x 10 HSPCs per kilogram of body weight in a human subject 6 ≥ 4.25 x 10 HSPCs per kilogram of body weight in a human subject 6 ≥ 4.5 x 10 HSPCs per kilogram of body weight in a human subject 6 ≥ 4.75 x 10 HSPCs per kilogram of body weight in a human subject 6 ≥ 5.0 x 10 HSPCs per kilogram of body weight in a human subject 6 ≥ 5.25 x 10 HSPCs per kilogram of body weight in a human subject 6 ≥ 5.5 x 10 HSPCs per kilogram of body weight in a human subject 6 ≥ 5.75 x 10 HSPCs per kilogram of body weight in a human subject 6 ≥ 6.0 x 10 HSPCs per kilogram of body weight in a human subject 6 ≥ 6.25 x 10 HSPCs per kilogram of body weight in a human subject 6 ≥ 6.5 x 10 HSPCs per kilogram of body weight in a human subject 6 ≥ 6.75 x 10 HSPCs per kilogram of body weight in a human subject 6≥ 7.0 x 10 HSPCs per kilogram of body weight in a human subject 6 ≥ 7.25 x 10 HSPCs per kilogram of body weight in a human subject 6 ≥ 7.5 x 10 HSPCs per kilogram of body weight in a human subject 6 ≥ 7.75 x 10 HSPCs per kilogram of body weight in a human subject 6 ≥ 8.0 x 10 HSPCs per kilogram of body weight in a human subject 6 ≥ 8.25 x 10 HSPCs per kilogram of body weight in a human subject 6 ≥ 8.5 x 10 HSPCs per kilogram of body weight in a human subject 6 ≥ 8.75 x 10 HSPCs per kilogram of body weight in a human subject 6 ≥ 9.0 x 10 HSPCs per kilogram of body weight in a human subject 6 ≥ 9.25 x 10 HSPCs per kilogram of body weight in a human subject 6 ≥ 9.5 x 10 HSPCs per kilogram of body weight in a human subject 6 ≥ 9.75 x 10 HSPCs per kilogram of body weight in a human subject 6 ≥ 1.0 x 10 HSPCs per kilogram of body weight in a human subject 7 ≥ 1.25 x 10 HSPCs per kilogram of body weight in a human subject 7 ≥ 1.5 x 10 HSPCs per kilogram of body weight in a human subject 7 ≥ 1.75 x 10 HSPCs per kilogram of body weight in a human subject 7 ≥ 2.0 x 10 HSPCs per kilogram of body weight in a human subject 7 ≥ 2.25 x 10 HSPCs per kilogram of body weight in a human subject 7 ≥ 2.5 x 10 HSPCs per kilogram of body weight in a human subject 7 ≥ 2.75 x 10 HSPCs per kilogram of body weight in a human subject 7 ≥ 3.0 x 10 HSPCs per kilogram of body weight in a human subject 7 ≥ 3.25 x 10 HSPCs per kilogram of body weight in a human subject 7≥ 3.5 x 10 HSPCs per kilogram of body weight in a human subject 7 ≥ 3.75 x 10 HSPCs per kilogram of body weight in a human subject 7 ≥ 4.0 x 10 HSPCs per kilogram of body weight in a human subject 7 ≥ 4.25 x 10 HSPCs per kilogram of body weight in a human subject 7 ≥ 4.5 x 10 HSPCs per kilogram of body weight in a human subject 7 ≥ 4.75 x 10 HSPCs per kilogram of body weight in a human subject 7 ≥ 5.0 x 10 HSPCs per kilogram of body weight in a human subject 7 ≥ 5.25 x 10 HSPCs per kilogram of body weight in a human subject 7 ≥ 5.5 x 10 HSPCs per kilogram of body weight in a human subject 7 ≥ 5.75 x 10 HSPCs per kilogram of body weight in a human subject 7 ≥ 6.0 x 10 HSPCs per kilogram of body weight in a human subject 7 ≥ 6.25 x 10 HSPCs per kilogram of body weight in a human subject 7 ≥ 6.5 x 10 HSPCs per kilogram of body weight in a human subject 7 ≥ 6.75 x 10 HSPCs per kilogram of body weight in a human subject 7 ≥ 7.0 x 10 HSPCs per kilogram of body weight in a human subject 7 ≥ 7.25 x 10 HSPCs per kilogram of body weight in a human subject 7 ≥ 7.5 x 10 HSPCs per kilogram of body weight in a human subject 7 ≥ 7.75 x 10 HSPCs per kilogram of body weight in a human subject 7 ≥ 8.0 x 10 HSPCs per kilogram of body weight in a human subject 7 ≥ 8.25 x 10 HSPCs per kilogram of body weight in a human subject 7 ≥ 8.5 x 10 HSPCs per kilogram of body weight in a human subject 7 ≥ 8.75 x 10 HSPCs per kilogram of body weight in a human subject 7≥ 9.0 x 10 HSPCs per kilogram of body weight in a human subject 7 ≥ 9.25 x 10 HSPCs per kilogram of body weight in a human subject 7 ≥ 9.5 x 10 HSPCs per kilogram of body weight in a human subject 7 ≥ 9.75 x 10 HSPCs per kilogram of body weight in a human subject 7 ≥ 1.0 x 10 HSPCs per kilogram of body weight in a human subject 8 ≥ 1.25 x 10 HSPCs per kilogram of body weight in a human subject 8 ≥ 1.5 x 10 HSPCs per kilogram of body weight in a human subject 8 ≥ 1.75 x 10 HSPCs per kilogram of body weight in a human subject 8 ≥ 2.0 x 10 HSPCs per kilogram of body weight in a human subject 8 ≥ 2.25 x 10 HSPCs per kilogram of body weight in a human subject 8 ≥ 2.5 x 10 HSPCs per kilogram of body weight in a human subject 8 ≥ 2.75 x 10 HSPCs per kilogram of body weight in a human subject 8 ≥ 3.0 x 10 HSPCs per kilogram of body weight in a human subject 8 ≥ 3.25 x 10 HSPCs per kilogram of body weight in a human subject 8 ≥ 3.5 x 10 HSPCs per kilogram of body weight in a human subject 8 ≥ 3.75 x 10 HSPCs per kilogram of body weight in a human subject 8 ≥ 4.0 x 10 HSPCs per kilogram of body weight in a human subject 8 ≥ 4.25 x 10 HSPCs per kilogram of body weight in a human subject 8 ≥ 4.5 x 10 HSPCs per kilogram of body weight in a human subject 8 ≥ 4.75 x 10 HSPCs per kilogram of body weight in a human subject 8 HSPCs or approximately 5.0 x 10 per kilogram of body weight in a human subject 8The amount or dose that comprises more than 100 HSPCs is administered to the subject.In some embodiments, the body weight of the human subject is the actual body weight of the human subject.In other embodiments, the body weight of the human subject is the ideal actual body weight of the human subject.

[0067] Naive conventional αβ-T cells or naive conventional CD3 + CD25 - CD45RA + Subsets of immune cells, such as T cells (Tcon), regulatory T cells (Treg), invariant natural killer T cells (iNKT), and memory T cells (Tmem), may contribute to aspects of GVHD after HCT, including the GVHD immune response, immune reconstitution, susceptibility to infection, and patient survival.

[0068] Regulatory T cells ("Tregs") are a specialized subpopulation of T cells that negatively regulate (e.g., suppress) immune system activation, thereby promoting immune tolerance. Numerous Treg subsets exist, such as TCRαβ+CD4+ regulatory T cells, including natural regulatory T cells (nTregs) and induced regulatory T cells (iTregs). nTregs and iTregs are CD4+CD25+, and both can inhibit the proliferation of CD4+CD25- T cells in a dose-dependent manner. In some embodiments, Tregs are anergic and do not proliferate upon TCR stimulation. In addition to being positive for CD4 and CD25, Tregs can be positive for the intracellular marker, the transcription factor FOXP3. Tregs can be identified or selected based on various marker expression profiles. Non-limiting examples of marker expression profiles that can be used to select Tregs include: (1) CD4+CD25+CD127dim, (2) CD4+FOXP3+, (3) CD3+CD4+CD25+, (5) CD3+CD4+CD25+CD127dim, and (6) CD3+CD4+CD25+CD127dim. These include FOXP3+, (7) CD3+FOXP3+, (8) CD3+CD4+FOXP3+, (9) CD3+CD4+CD25+FOXP3+, (10) CD3+CD25+FOXP3+, (11) CD3+CD25+CD127dim, (12) CD4+CD25+, (13) CD4+CD25+CD127dimFOXP3+, (14) FOXP3+, CD4+FOXP3+, (15) CD4+CD25+FOXP3+, (16) CD25+FOXP3+, and (17) CD25+CD127dim.Selection based on specific expression profiles can be achieved based on extracellular markers, without the need for cell permeability, for example, by selection based on CD4+CD25+CD127dim.

[0069] Cell populations comprising Tregs can, for example, reduce the incidence of graft rejection, reduce the incidence and / or severity of GVHD, promote hematopoietic reconstitution, promote immune reconstitution, promote mixed chimerism, or a combination thereof.

[0070] In some embodiments, Tregs are CD4+CD25+CD127dim or CD4+FOXP3+. + CD25 + CD127 dim and FOXP3 + In some embodiments, the Tregs of the present disclosure are fresh Tregs. In some embodiments, the Tregs of the present disclosure are fresh CD4 + CD25 + CD127 dim Regulatory T cells (Tregs).

[0071] In some embodiments, Tregs are present in a composition, cell therapy product, and / or at a concentration of about 1.0 x 10 per kilogram of body weight of a human subject. 5 ~Approx. 1.0×10 8 Tregs, approximately 1.0 x 10 per kilogram of body weight in a human subject 5 ~Approx. 2.0×10 7 Tregs, approximately 1.0 x 10 per kilogram of body weight in a human subject 5 ~Approx. 1.0×10 7 Tregs, or approximately 5.0 x 10 per kilogram of body weight in a human subject 5 ~Approx. 4.0×10 6 In some embodiments, the Tregs are administered to a subject in an amount or dose that may comprise about 1.0 x 10 Tregs per kilogram of body weight of a human subject. In some embodiments, the Tregs are present in a composition, cell therapy product, and / or are administered to a subject in an amount or dose that may comprise about 1.0 x 10 Tregs per kilogram of body weight of a human subject. 5 ≥ 1.5 x 10 Tregs per kilogram of body weight in a human subject 5 ≥ 2.0 × 10 Tregs per kilogram of body weight in a human subject 5 ≥ 2.5 x 10 Tregs per kilogram of body weight in a human subject 5 ≥ 3.0 × 10 Tregs per kilogram of body weight in a human subject 5 ≥ 3.5 × 10 Tregs per kilogram of body weight in a human subject 5 ≥ 4.0 × 10 Tregs per kilogram of body weight in a human subject 5≥ 4.5 x 10 Tregs per kilogram of body weight in a human subject 5 ≥ 5.0 × 10 Tregs per kilogram of body weight in a human subject 5 ≥ 5.5 x 10 Tregs per kilogram of body weight in a human subject 5 ≥ 6.0 × 10 Tregs per kilogram of body weight in a human subject 5 ≥ 6.5 × 10 Tregs per kilogram of body weight in a human subject 5 ≥ 7.0 × 10 Tregs per kilogram of body weight in a human subject 5 ≥ 7.5 x 10 Tregs per kilogram of body weight in a human subject 5 ≥ 8.0 × 10 Tregs per kilogram of body weight in a human subject 5 ≥ 8.5 × 10 Tregs per kilogram of body weight in a human subject 5 ≥ 9.0 × 10 Tregs per kilogram of body weight in a human subject 5 ≥ 9.5 × 10 Tregs per kilogram of body weight in a human subject 5 ≥ 1.0 x 10 Tregs per kilogram of body weight in a human subject 6 ≥ 1.25 x 10 Tregs per kilogram of body weight in a human subject 6 ≥ 1.5 x 10 Tregs per kilogram of body weight in a human subject 6 ≥ 1.75 x 10 Tregs per kilogram of body weight in a human subject 6 ≥ 2.0 × 10 Tregs per kilogram of body weight in a human subject 6 ≥ 2.25 x 10 Tregs per kilogram of body weight in a human subject 6 ≥ 2.5 x 10 Tregs per kilogram of body weight in a human subject 6 ≥ 2.75 x 10 Tregs per kilogram of body weight in a human subject 6 ≥ 3.0 × 10 Tregs per kilogram of body weight in a human subject 6 ≥ 3.25 x 10 Tregs per kilogram of body weight in a human subject 6 ≥ 3.5 × 10 Tregs per kilogram of body weight in a human subject 6≥ 3.75 x 10 Tregs per kilogram of body weight in a human subject 6 ≥ 4.0 × 10 Tregs per kilogram of body weight in a human subject 6 ≥ 4.25 x 10 Tregs per kilogram of body weight in a human subject 6 ≥ 4.5 x 10 Tregs per kilogram of body weight in a human subject 6 ≥ 4.75 x 10 Tregs per kilogram of body weight in a human subject 6 ≥ 5.0 × 10 Tregs per kilogram of body weight in a human subject 6 ≥ 5.25 × 10 Tregs per kilogram of body weight in a human subject 6 ≥ 5.5 x 10 Tregs per kilogram of body weight in a human subject 6 ≥ 5.75 x 10 Tregs per kilogram of body weight in a human subject 6 ≥ 6.0 × 10 Tregs per kilogram of body weight in a human subject 6 ≥ 6.25 × 10 Tregs per kilogram of body weight in a human subject 6 ≥ 6.5 × 10 Tregs per kilogram of body weight in a human subject 6 ≥ 6.75 x 10 Tregs per kilogram of body weight in a human subject 6 ≥ 7.0 × 10 Tregs per kilogram of body weight in a human subject 6 ≥ 7.25 x 10 Tregs per kilogram of body weight in a human subject 6 ≥ 7.5 x 10 Tregs per kilogram of body weight in a human subject 6 ≥ 7.75 x 10 Tregs per kilogram of body weight in a human subject 6 ≥ 8.0 × 10 Tregs per kilogram of body weight in a human subject 6 ≥ 8.25 x 10 Tregs per kilogram of body weight in a human subject 6 ≥ 8.5 × 10 Tregs per kilogram of body weight in a human subject 6 ≥ 8.75 x 10 Tregs per kilogram of body weight in a human subject 6 ≥ 9.0 × 10 Tregs per kilogram of body weight in a human subject 6≥ 9.25 x 10 Tregs per kilogram of body weight in a human subject 6 ≥ 9.5 × 10 Tregs per kilogram of body weight in a human subject 6 ≥ 9.75 x 10 Tregs per kilogram of body weight in a human subject 6 ≥ 1.0 x 10 Tregs per kilogram of body weight in a human subject 7 ≥ 1.25 x 10 Tregs per kilogram of body weight in a human subject 7 ≥ 1.5 x 10 Tregs per kilogram of body weight in a human subject 7 ≥ 1.75 x 10 Tregs per kilogram of body weight in a human subject 7 ≥ 2.0 × 10 Tregs per kilogram of body weight in a human subject 7 ≥ 2.25 x 10 Tregs per kilogram of body weight in a human subject 7 ≥ 2.5 x 10 Tregs per kilogram of body weight in a human subject 7 ≥ 2.75 x 10 Tregs per kilogram of body weight in a human subject 7 ≥ 3.0 × 10 Tregs per kilogram of body weight in a human subject 7 ≥ 3.25 x 10 Tregs per kilogram of body weight in a human subject 7 ≥ 3.5 × 10 Tregs per kilogram of body weight in a human subject 7 ≥ 3.75 x 10 Tregs per kilogram of body weight in a human subject 7 ≥ 4.0 × 10 Tregs per kilogram of body weight in a human subject 7 ≥ 4.25 x 10 Tregs per kilogram of body weight in a human subject 7 ≥ 4.5 x 10 Tregs per kilogram of body weight in a human subject 7 ≥ 4.75 x 10 Tregs per kilogram of body weight in a human subject 7 ≥ 5.0 × 10 Tregs per kilogram of body weight in a human subject 7 ≥ 5.25 × 10 Tregs per kilogram of body weight in a human subject 7 ≥ 5.5 x 10 Tregs per kilogram of body weight in a human subject 7≥ 5.75 x 10 Tregs per kilogram of body weight in a human subject 7 ≥ 6.0 × 10 Tregs per kilogram of body weight in a human subject 7 ≥ 6.25 × 10 Tregs per kilogram of body weight in a human subject 7 ≥ 6.5 × 10 Tregs per kilogram of body weight in a human subject 7 ≥ 6.75 x 10 Tregs per kilogram of body weight in a human subject 7 ≥ 7.0 × 10 Tregs per kilogram of body weight in a human subject 7 ≥ 7.25 x 10 Tregs per kilogram of body weight in a human subject 7 ≥ 7.5 x 10 Tregs per kilogram of body weight in a human subject 7 ≥ 7.75 x 10 Tregs per kilogram of body weight in a human subject 7 ≥ 8.0 × 10 Tregs per kilogram of body weight in a human subject 7 ≥ 8.25 x 10 Tregs per kilogram of body weight in a human subject 7 ≥ 8.5 × 10 Tregs per kilogram of body weight in a human subject 7 ≥ 8.75 x 10 Tregs per kilogram of body weight in a human subject 7 ≥ 9.0 × 10 Tregs per kilogram of body weight in a human subject 7 ≥ 9.25 x 10 Tregs per kilogram of body weight in a human subject 7 ≥ 9.5 × 10 Tregs per kilogram of body weight in a human subject 7 ≥ 9.75 x 10 Tregs per kilogram of body weight in a human subject 7 ≥ 1.0 x 10 Tregs per kilogram of body weight in a human subject 8 The subject is administered an amount or dose containing at least one Treg. In some embodiments, the body weight of the human subject is the actual body weight of the human subject. In other embodiments, the body weight of the human subject is the ideal actual body weight of the human subject.

[0072] The cell populations of the present disclosure may include memory T cells (Tmems). Tmems may refer to antigen-experienced T cells that express, for example, the phenotypic markers CD45RO, TCRα, TCRβ, CD3, CD4, CD95, and IL-2Rβ, or the phenotypic markers CD45RO, TCRα, TCRβ, CD3, CD8, CD95, and IL-2Rβ. Tmems confer immunity and can persist in an inactive state for long periods of time. Tmems can rapidly acquire effector function upon rechallenge with antigen. A population of Tmems may include any combination of the subclasses T central memory cells and T effector memory cells. In some embodiments, Tmems of the present disclosure are CD45RA-. In some embodiments, Tmems of the present disclosure are CD3+CD45RA-CD45RO+. In various methods, Tmems administered to a subject undergoing HCT can, for example, promote GVT, reduce GVHD, reduce susceptibility to cancer recurrence, reduce susceptibility to infection, or a combination thereof.

[0073] In some embodiments, Tmem is present in a composition, cell therapy product, and / or is present in a human subject at a concentration of about 1.0 x 10 per kilogram of body weight. 5 ~Approx. 5.0×10 8 Tmems, approximately 1.0 × 10 per kilogram of body weight in a human subject 5 ~Approx. 1.0×10 8 Tmems, or approximately 5.0 × 10 per kilogram of body weight in a human subject 5 ~Approx. 2.0×10 7 In some embodiments, the Tmem is present in a composition, cell therapy product, and / or administered to a subject in an amount or dose that may comprise about 1.0 x 10 Tmems per kilogram of body weight of a human subject. 5 ≥ 1.5 × 10 Tmems per kilogram of body weight in a human subject 5 ≥ 2.0 × 10 Tmems per kilogram of body weight in a human subject 5 ≥ 2.5 × 10 Tmems per kilogram of body weight in a human subject 5≥ 3.0 × 10 Tmems per kilogram of body weight in a human subject 5 ≥ 3.5 × 10 Tmems per kilogram of body weight in a human subject 5 ≥ 4.0 × 10 Tmems per kilogram of body weight in a human subject 5 ≥ 4.5 × 10 Tmems per kilogram of body weight in a human subject 5 ≥ 5.0 × 10 Tmems per kilogram of body weight in a human subject 5 ≥ 5.5 × 10 Tmems per kilogram of body weight in a human subject 5 ≥ 6.0 × 10 Tmems per kilogram of body weight in a human subject 5 ≥ 6.5 × 10 Tmems per kilogram of body weight in a human subject 5 ≥ 7.0 × 10 Tmems per kilogram of body weight in a human subject 5 ≥ 7.5 × 10 Tmems per kilogram of body weight in a human subject 5 ≥ 8.0 × 10 Tmems per kilogram of body weight in a human subject 5 ≥ 8.5 × 10 Tmems per kilogram of body weight in a human subject 5 ≥ 9.0 × 10 Tmems per kilogram of body weight in a human subject 5 ≥ 9.5 × 10 Tmems per kilogram of body weight in a human subject 5 ≥ 1.0 × 10 Tmems per kilogram of body weight in a human subject 6 ≥ 1.25 × 10 Tmems per kilogram of body weight in a human subject 6 ≥ 1.5 × 10 Tmems per kilogram of body weight in a human subject 6 ≥ 1.75 × 10 Tmems per kilogram of body weight in a human subject 6 ≥ 2.0 × 10 Tmems per kilogram of body weight in a human subject 6 ≥ 10 Tmems, approximately 2.25 × 10 per kilogram of body weight in a human subject 6 ≥ 2.5 × 10 Tmems per kilogram of body weight in a human subject 6 ≥ 10 Tmems, approximately 2.75 × 10 per kilogram of body weight in a human subject 6≥ 3.0 × 10 Tmems per kilogram of body weight in a human subject 6 ≥ 3.25 × 10 Tmems per kilogram of body weight in a human subject 6 ≥ 3.5 × 10 Tmems per kilogram of body weight in a human subject 6 ≥ 3.75 × 10 Tmems per kilogram of body weight in a human subject 6 ≥ 4.0 × 10 Tmems per kilogram of body weight in a human subject 6 ≥ 4.25 × 10 Tmems per kilogram of body weight in a human subject 6 ≥ 4.5 × 10 Tmems per kilogram of body weight in a human subject 6 ≥ 4.75 × 10 Tmems per kilogram of body weight in a human subject 6 ≥ 5.0 × 10 Tmems per kilogram of body weight in a human subject 6 ≥ 5.25 × 10 Tmems per kilogram of body weight in a human subject 6 ≥ 5.5 × 10 Tmems per kilogram of body weight in a human subject 6 ≥ 5.75 × 10 Tmems per kilogram of body weight in a human subject 6 ≥ 6.0 × 10 Tmems per kilogram of body weight in a human subject 6 ≥ 6.25 × 10 Tmems per kilogram of body weight in a human subject 6 ≥ 6.5 × 10 Tmems per kilogram of body weight in a human subject 6 ≥ 6.75 × 10 Tmems per kilogram of body weight in a human subject 6 ≥ 7.0 × 10 Tmems per kilogram of body weight in a human subject 6 ≥ 7.25 × 10 Tmems per kilogram of body weight in a human subject 6 ≥ 7.5 × 10 Tmems per kilogram of body weight in a human subject 6 ≥ 7.75 × 10 Tmems per kilogram of body weight in a human subject 6 ≥ 8.0 × 10 Tmems per kilogram of body weight in a human subject 6 ≥ 8.25 × 10 Tmems per kilogram of body weight in a human subject 6≥ 8.5 × 10 Tmems per kilogram of body weight in a human subject 6 ≥ 8.75 × 10 Tmems per kilogram of body weight in a human subject 6 ≥ 9.0 × 10 Tmems per kilogram of body weight in a human subject 6 ≥ 9.25 × 10 Tmems per kilogram of body weight in a human subject 6 ≥ 9.5 × 10 Tmems per kilogram of body weight in a human subject 6 ≥ 9.75 × 10 Tmems per kilogram of body weight in a human subject 6 ≥ 1.0 × 10 Tmems per kilogram of body weight in a human subject 7 ≥ 1.25 × 10 Tmems per kilogram of body weight in a human subject 7 ≥ 1.5 × 10 Tmems per kilogram of body weight in a human subject 7 ≥ 1.75 × 10 Tmems per kilogram of body weight in a human subject 7 ≥ 2.0 × 10 Tmems per kilogram of body weight in a human subject 7 ≥ 10 Tmems, approximately 2.25 × 10 per kilogram of body weight in a human subject 7 ≥ 2.5 × 10 Tmems per kilogram of body weight in a human subject 7 ≥ 10 Tmems, approximately 2.75 × 10 per kilogram of body weight in a human subject 7 ≥ 3.0 × 10 Tmems per kilogram of body weight in a human subject 7 ≥ 3.25 × 10 Tmems per kilogram of body weight in a human subject 7 ≥ 3.5 × 10 Tmems per kilogram of body weight in a human subject 7 ≥ 3.75 × 10 Tmems per kilogram of body weight in a human subject 7 ≥ 4.0 × 10 Tmems per kilogram of body weight in a human subject 7 ≥ 4.25 × 10 Tmems per kilogram of body weight in a human subject 7 ≥ 4.5 × 10 Tmems per kilogram of body weight in a human subject 7 ≥ 4.75 × 10 Tmems per kilogram of body weight in a human subject 7≥ 5.0 × 10 Tmems per kilogram of body weight in a human subject 7 ≥ 5.25 × 10 Tmems per kilogram of body weight in a human subject 7 ≥ 5.5 × 10 Tmems per kilogram of body weight in a human subject 7 ≥ 5.75 × 10 Tmems per kilogram of body weight in a human subject 7 ≥ 6.0 × 10 Tmems per kilogram of body weight in a human subject 7 ≥ 6.25 × 10 Tmems per kilogram of body weight in a human subject 7 ≥ 6.5 × 10 Tmems per kilogram of body weight in a human subject 7 ≥ 6.75 × 10 Tmems per kilogram of body weight in a human subject 7 ≥ 7.0 × 10 Tmems per kilogram of body weight in a human subject 7 ≥ 7.25 × 10 Tmems per kilogram of body weight in a human subject 7 ≥ 7.5 × 10 Tmems per kilogram of body weight in a human subject 7 ≥ 7.75 × 10 Tmems per kilogram of body weight in a human subject 7 ≥ 8.0 × 10 Tmems per kilogram of body weight in a human subject 7 ≥ 8.25 × 10 Tmems per kilogram of body weight in a human subject 7 ≥ 8.5 × 10 Tmems per kilogram of body weight in a human subject 7 ≥ 8.75 × 10 Tmems per kilogram of body weight in a human subject 7 ≥ 9.0 × 10 Tmems per kilogram of body weight in a human subject 7 ≥ 9.25 × 10 Tmems per kilogram of body weight in a human subject 7 ≥ 9.5 × 10 Tmems per kilogram of body weight in a human subject 7 ≥ 9.75 × 10 Tmems per kilogram of body weight in a human subject 7 ≥ 1.0 × 10 Tmems per kilogram of body weight in a human subject 8 ≥ 1.25 × 10 Tmems per kilogram of body weight in a human subject 8≥ 1.5 × 10 Tmems per kilogram of body weight in a human subject 8 ≥ 1.75 × 10 Tmems per kilogram of body weight in a human subject 8 ≥ 2.0 × 10 Tmems per kilogram of body weight in a human subject 8 ≥ 10 Tmems, approximately 2.25 × 10 per kilogram of body weight in a human subject 8 ≥ 2.5 × 10 Tmems per kilogram of body weight in a human subject 8 ≥ 10 Tmems, approximately 2.75 × 10 per kilogram of body weight in a human subject 8 ≥ 3.0 × 10 Tmems per kilogram of body weight in a human subject 8 ≥ 3.25 × 10 Tmems per kilogram of body weight in a human subject 8 ≥ 3.5 × 10 Tmems per kilogram of body weight in a human subject 8 ≥ 3.75 × 10 Tmems per kilogram of body weight in a human subject 8 ≥ 4.0 × 10 Tmems per kilogram of body weight in a human subject 8 ≥ 4.25 × 10 Tmems per kilogram of body weight in a human subject 8 ≥ 4.5 × 10 Tmems per kilogram of body weight in a human subject 8 ≥ 4.75 × 10 Tmems per kilogram of body weight in a human subject 8 ≥ 5.0 × 10 Tmems per kilogram of body weight in a human subject 8 The subject is administered an amount or dose containing one or more Tmems. In some embodiments, the body weight of the human subject is the actual body weight of the human subject. In other embodiments, the body weight of the human subject is the ideal actual body weight of the human subject.

[0074] The cell populations of the present disclosure may include invariant natural killer T cells (iNKT). iNKT is a subclass of CD1d-restricted natural killer T (NKT) cells that express a highly conserved αβ-T cell receptor containing the Vα24Jα18 TCR α chain (referred to herein as "Vα24Jα18+"). iNKT cells can be identified by binding to CD1d multimers loaded with α-galactosylceramide (GalCer), PBS-57, PBS-44, or other natural or synthetic glycolipids. Another identification method is an antibody or combination of antibodies that specifically recognizes the Vα24Jα18 region. Examples include Vα24 antibodies, Jα18 antibodies, or the monoclonal antibody clone 6B11, which specifically binds to a unique region of the Vα24Jα18 TCR and can be used to identify iNKT cells. iNKT may be CD3+Vα24Jα18+. In some embodiments, the iNKT of the present disclosure is TCR Vα24Jα18 + CD127 + is.

[0075] In some embodiments, iNKT can promote engraftment, promote GVT, reduce the incidence and / or severity of GVHD, reduce susceptibility to cancer recurrence, reduce susceptibility to infection, or a combination thereof. In some embodiments, iNKT promotes the activity of Tregs. In some embodiments, iNKT promotes the activity of HSPCs.

[0076] In some embodiments, iNKT is present in a composition, cell therapy product, and / or at a concentration of about 1 x 10 per kilogram of actual or ideal body weight of a human subject. 4 ~Approx. 1×10 9 In some embodiments, the iNKT is present in a composition, cell therapy product, and / or administered to a subject in an amount or dose that may comprise about 5.0 x 10 iNKT per kilogram of body weight of a human subject. 2 ~Approx. 2.0×10 6In some embodiments, the iNKT is present in a composition, cell therapy product, and / or administered to a subject in an amount or dose that may comprise about 5.0 x 10 iNKT per kilogram of body weight of a human subject. 2 ≥ 6.0 × 10 iNKTs per kilogram of body weight in a human subject 2 ≥ 7.0 × 10 iNKTs per kilogram of body weight in a human subject 2 ≥ 8.0 × 10 iNKTs per kilogram of body weight in a human subject 2 or more iNKTs, approximately 9.0 × 10 per kilogram of body weight in a human subject 2 ≥ 1.0 × 10 iNKT per kilogram of body weight in a human subject 3 ≥ 2.0 × 10 iNKTs per kilogram of body weight in a human subject 3 ≥ 3.0 × 10 iNKTs per kilogram of body weight in a human subject 3 ≥ 4.0 × 10 iNKTs per kilogram of body weight in a human subject 3 ≥ 5.0 × 10 iNKTs per kilogram of body weight in a human subject 3 ≥ 6.0 × 10 iNKTs per kilogram of body weight in a human subject 3 ≥ 7.0 × 10 iNKTs per kilogram of body weight in a human subject 3 ≥ 8.0 × 10 iNKTs per kilogram of body weight in a human subject 3 or more iNKTs, approximately 9.0 × 10 per kilogram of body weight in a human subject 3 ≥ 1.0 × 10 iNKT per kilogram of body weight in a human subject 4 ≥ 2.0 × 10 iNKTs per kilogram of body weight in a human subject 4 ≥ 3.0 × 10 iNKTs per kilogram of body weight in a human subject 4 ≥ 4.0 × 10 iNKTs per kilogram of body weight in a human subject 4 ≥ 5.0 × 10 iNKTs per kilogram of body weight in a human subject 4 ≥ 6.0 × 10 iNKTs per kilogram of body weight in a human subject 4 ≥ 7.0 × 10 iNKTs per kilogram of body weight in a human subject 4≥ 8.0 × 10 iNKTs per kilogram of body weight in a human subject 4 or more iNKTs, approximately 9.0 × 10 per kilogram of body weight in a human subject 4 ≥ 1.0 × 10 iNKT per kilogram of body weight in a human subject 5 ≥ 2.0 × 10 iNKTs per kilogram of body weight in a human subject 5 ≥ 3.0 × 10 iNKTs per kilogram of body weight in a human subject 5 ≥ 4.0 × 10 iNKTs per kilogram of body weight in a human subject 5 ≥ 5.0 × 10 iNKTs per kilogram of body weight in a human subject 5 ≥ 6.0 × 10 iNKTs per kilogram of body weight in a human subject 5 ≥ 7.0 × 10 iNKTs per kilogram of body weight in a human subject 5 ≥ 8.0 × 10 iNKTs per kilogram of body weight in a human subject 5 or more iNKTs, approximately 9.0 × 10 per kilogram of body weight in a human subject 5 ≥ 1.0 × 10 iNKT per kilogram of body weight in a human subject 6 ≥ 1.5 x 10 iNKT per kilogram of body weight in a human subject 6 ≥ 10 iNKTs, or approximately 2.0 × 10 per kilogram of body weight in a human subject 6 The subject is administered an amount or dose containing one or more iNKTs.

[0077] As used herein, "naive conventional αβ-T cells" or "naive conventional CD3 + CD25 - CD45RA + The term "T cells" refers to cells that express the phenotypic markers TCRα / β, CD45RA, and intermediate to high levels of CD127 (CD127 + ), and do not express or have low expression of CD45RO and CD25. In some embodiments, naive conventional αβ-T cells or naive conventional CD3 + CD25 - CD45RA+ T cells (Tcon) are characterized by expression of phenotypic markers of naive conventional αβ-T cells, including TCRα, TCRβ, CD3, CD4 or CDCD8, CD62L, CCR7, CD28, CD127, and CD45RA. In some embodiments, naive conventional αβ-T cells or naive conventional CD3 + CD25 - CD45RA + T cells (Tcon) are CD3 + CD25 - CD45RA + and comprises a polymorphic TCR α and / or a polymorphic TCR β. In some embodiments, naive conventional αβ-T cells or naive conventional CD3 + CD25 - CD45RA + T cells (Tcon) do not express the Vα24Jα18 TCR found on iNKT cells. In some embodiments, naive conventional αβ-T cells or naive conventional CD3 + CD25 - CD45RA + T cells (Tcon) are CD45RA+ and are sorted from a cell sample that has already been sorted for HSPCs, Tregs, and Tmem cells.

[0078] In some embodiments, naive conventional αβ-T cells or naive conventional CD3 + CD25 - CD45RA + T cells (Tcon) express CD25 - , CD45RA + In some embodiments, the naive conventional αβ-T cells or the naive conventional CD3 + CD25 - CD45RA + T cells (Tcon) express TCRα / β + CD45RA + and CD25 - , CD127 + , or both. Naive conventional αβ-T cells or naive conventional CD3 + CD25- CD45RA + T cells (Tcon) express TCRα + TCRβ + CD45RA +CD4 5RO - CD25 - CD95 - IL-2Rβ - CD127 + Vα24Jα18 - CD45RA+ naive conventional αβ-T cells or Tcon can be further described as depletion of naive conventional αβ-T cells or naive conventional CD3 + CD25 - CD45RA + Due to depletion of T cells (Tcon), they may be discarded during or after cell sorting.

[0079] In some embodiments, naive conventional αβ-T cells or naive conventional CD3 + CD25 - CD45RA + T cells (Tcon) are present in the composition, cell therapy product, and / or at a concentration of about 5.0 x 10 per kilogram of body weight of a human subject. 5 < naive conventional CD3 + CD25 - CD45RA + In some embodiments, the amount of naive conventional αβ-T cells or naive conventional CD3 T cells (Tcon) is administered to the subject. + CD25 - CD45RA + T cells (Tcon) are present in the composition, cell therapy product, and / or at a concentration of about 1.0 x 10 per kilogram of body weight of a human subject. 5 < naive conventional CD3 + CD25 - CD45RA + In some embodiments, the Tcon is administered to a subject in an amount of about 5.0 x 10 T cells (Tcon) per kilogram of body weight of a human subject. In some embodiments, the Tcon is present in a composition, a cell therapy product, and / or a cell therapy product. 5 Tcon less than 4.9 x 10 per kilogram of body weight in human subjects 5Tcon less than 4.8 x 10 per kilogram of body weight in human subjects 5 Tcon less than 4.7 x 10 per kilogram of body weight in human subjects 5 Tcon less than 4.6 x 10 per kilogram of body weight in human subjects 5 Less than 4.5 x 10 per kilogram of body weight in a human subject 5 Tcon less than 4.4 x 10 per kilogram of body weight in human subjects 5 Tcon less than 4.3 x 10 per kilogram of body weight in human subjects 5 Less than 4.2 x 10 per kilogram of body weight in a human subject 5 Tcon less than 4.1 x 10 per kilogram of body weight in human subjects 5 Tcon less than 4.0 x 10 per kilogram of body weight in human subjects 5 Tcon less than 3.9 x 10 per kilogram of body weight in human subjects 5 Less than 3.8 x 10 per kilogram of body weight in a human subject 5 Less than 3.7 x 10 per kilogram of body weight in a human subject 5 Tcon less than 3.6 x 10 per kilogram of body weight in human subjects 5 Less than 3.5 x 10 per kilogram of body weight in a human subject 5 Tcon less than 3.4 x 10 per kilogram of body weight in human subjects 5 Less than 3.3 x 10 per kilogram of body weight in a human subject 5 Less than 3.2 x 10 per kilogram of body weight in a human subject 5 Less than 3.1 x 10 per kilogram of body weight in a human subject 5 Tcon less than approximately 3.0 x 10 per kilogram of body weight in human subjects 5 Tcon less than 2.9 x 10 per kilogram of body weight in human subjects 5 Tcon less than 2.8 x 10 per kilogram of body weight in human subjects 5 Tcon less than 2.7 x 10 per kilogram of body weight in human subjects 5Tcon less than 2.6 x 10 per kilogram of body weight in human subjects 5 Less than 2.5 x 10 per kilogram of body weight in a human subject 5 Tcon less than 2.4 x 10 per kilogram of body weight in human subjects 5 Tcon less than 2.3 x 10 per kilogram of body weight in human subjects 5 Less than 2.2 x 10 per kilogram of body weight in a human subject 5 Less than 2.1 x 10 per kilogram of body weight in a human subject 5 Less than 2.0 x 10 per kilogram of body weight in a human subject 5 Tcon less than 1.9 x 10 per kilogram of body weight in human subjects 5 Less than 1.8 x 10 per kilogram of body weight in a human subject. 5 Less than 1.7 x 10 per kilogram of body weight in a human subject. 5 Tcon less than 1.6 x 10 per kilogram of body weight in human subjects 5 Less than 1.5 x 10 per kilogram of body weight in a human subject 5 Tcon less than 1.4 x 10 per kilogram of body weight in human subjects 5 Less than 1.3 x 10 per kilogram of body weight in a human subject 5 Less than 1.2 x 10 per kilogram of body weight in a human subject 5 Tcon less than 1.1 x 10 per kilogram of body weight in human subjects 5 Tcon less than approximately 1.0 x 10 per kilogram of body weight in human subjects 5 Tcon less than 9.9 x 10 per kilogram of body weight in human subjects 4 Tcon less than 9.8 x 10 per kilogram of body weight in human subjects 4 Tcon less than 9.7 x 10 per kilogram of body weight in human subjects 4 Tcon less than 9.6 x 10 per kilogram of body weight in human subjects 4 Tcon less than 9.5 x 10 per kilogram of body weight in human subjects 4Tcon less than 9.4 x 10 per kilogram of body weight in human subjects 4 Tcon less than 9.3 x 10 per kilogram of body weight in human subjects 4 Tcon less than 9.2 x 10 per kilogram of body weight in human subjects 4 Tcon less than 9.1 x 10 per kilogram of body weight in human subjects 4 Tcon less than 9.0 x 10 per kilogram of body weight in human subjects 4 Tcon less than 8.9 x 10 per kilogram of body weight in human subjects 4 Tcon less than 8.8 x 10 per kilogram of body weight in human subjects 4 Tcon less than 8.7 x 10 per kilogram of body weight in human subjects 4 Tcon less than 8.6 x 10 per kilogram of body weight in human subjects 4 Tcon less than 8.5 x 10 per kilogram of body weight in human subjects 4 Tcon less than 8.4 x 10 per kilogram of body weight in human subjects 4 Tcon less than 8.3 x 10 per kilogram of body weight in human subjects 4 Tcon less than 8.2 x 10 per kilogram of body weight in human subjects 4 Tcon less than 8.1 x 10 per kilogram of body weight in human subjects 4 Tcon less than 8.0 x 10 per kilogram of body weight in human subjects 4 Tcon less than 7.9 x 10 per kilogram of body weight in human subjects 4 Tcon less than 7.8 x 10 per kilogram of body weight in human subjects 4 Tcon less than 7.7 x 10 per kilogram of body weight in human subjects 4 Tcon less than 7.6 x 10 per kilogram of body weight in human subjects 4 Tcon less than 7.5 x 10 per kilogram of body weight in human subjects 4 Tcon less than 7.4 x 10 per kilogram of body weight in human subjects 4 Tcon less than 7.3 x 10 per kilogram of body weight in human subjects 4Tcon less than 7.2 x 10 per kilogram of body weight in human subjects 4 Tcon less than 7.1 x 10 per kilogram of body weight in human subjects 4 Tcon less than 7.0 x 10 per kilogram of body weight in human subjects 4 Tcon less than 6.9 x 10 per kilogram of body weight in human subjects 4 Tcon less than 6.8 x 10 per kilogram of body weight in human subjects 4 Tcon less than 6.7 x 10 per kilogram of body weight in human subjects 4 Tcon less than 6.6 x 10 per kilogram of body weight in human subjects 4 Tcon less than 6.5 x 10 per kilogram of body weight in human subjects 4 Tcon less than 6.4 x 10 per kilogram of body weight in human subjects 4 Tcon less than 6.3 x 10 per kilogram of body weight in human subjects 4 Tcon less than 6.2 x 10 per kilogram of body weight in human subjects 4 Tcon less than 6.1 x 10 per kilogram of body weight in human subjects 4 Tcon less than 6.0 x 10 per kilogram of body weight in human subjects 4 Tcon less than 5.9 x 10 per kilogram of body weight in human subjects 4 Tcon less than 5.8 x 10 per kilogram of body weight in human subjects 4 Tcon less than 5.7 x 10 per kilogram of body weight in human subjects 4 Tcon less than 5.6 x 10 per kilogram of body weight in human subjects 4 Tcon less than approximately 5.5 x 10 per kilogram of body weight in human subjects 4 Tcon less than 5.4 x 10 per kilogram of body weight in human subjects 4 Less than 5.3 x 10 per kilogram of body weight in a human subject 4 Tcon less than 5.2 x 10 per kilogram of body weight in human subjects 4 Less than 5.1 x 10 per kilogram of body weight in a human subject 4Less than 5.0 x 10 per kilogram of body weight in a human subject 4 Tcon less than 4.9 x 10 per kilogram of body weight in human subjects 4 Tcon less than 4.8 x 10 per kilogram of body weight in human subjects 4 Tcon less than 4.7 x 10 per kilogram of body weight in human subjects 4 Tcon less than 4.6 x 10 per kilogram of body weight in human subjects 4 Less than 4.5 x 10 per kilogram of body weight in a human subject 4 Tcon less than 4.4 x 10 per kilogram of body weight in human subjects 4 Tcon less than 4.3 x 10 per kilogram of body weight in human subjects 4 Less than 4.2 x 10 per kilogram of body weight in a human subject 4 Tcon less than 4.1 x 10 per kilogram of body weight in human subjects 4 Tcon less than 4.0 x 10 per kilogram of body weight in human subjects 4 Tcon less than 3.9 x 10 per kilogram of body weight in human subjects 4 Less than 3.8 x 10 per kilogram of body weight in a human subject 4 Tcon less than 3.7 x 10 per kilogram of body weight in human subjects 4 Tcon less than 3.6 x 10 per kilogram of body weight in human subjects 4 Less than 3.5 x 10 per kilogram of body weight in a human subject 4 Tcon less than 3.4 x 10 per kilogram of body weight in human subjects 4 Less than 3.3 x 10 per kilogram of body weight in a human subject 4 Less than 3.2 x 10 per kilogram of body weight in a human subject 4 Less than 3.1 x 10 per kilogram of body weight in a human subject 4 Tcon less than approximately 3.0 x 10 per kilogram of body weight in human subjects 4 Tcon less than 2.9 x 10 per kilogram of body weight in human subjects 4Tcon less than 2.8 x 10 per kilogram of body weight in human subjects 4 Tcon less than 2.7 x 10 per kilogram of body weight in human subjects 4 Tcon less than 2.6 x 10 per kilogram of body weight in human subjects 4 Less than 2.5 x 10 per kilogram of body weight in a human subject 4 Tcon less than 2.4 x 10 per kilogram of body weight in human subjects 4 Tcon less than 2.3 x 10 per kilogram of body weight in human subjects 4 Less than 2.2 x 10 per kilogram of body weight in a human subject 4 Less than 2.1 x 10 per kilogram of body weight in a human subject 4 Tcon less than approximately 2.0 x 10 per kilogram of body weight in human subjects 4 Tcon less than 1.9 x 10 per kilogram of body weight in human subjects 4 Less than 100 Tc on approximately 1.8 × 10 per kilogram of body weight in a human subject 4 Less than 1.7 x 10 per kilogram of body weight in a human subject. 4 Tcon less than 1.6 x 10 per kilogram of body weight in human subjects 4 Less than 1.5 x 10 per kilogram of body weight in a human subject 4 Tcon less than 1.4 x 10 per kilogram of body weight in human subjects 4 Less than 1.3 x 10 per kilogram of body weight in a human subject 4 Less than 1.2 x 10 per kilogram of body weight in a human subject 4 Tcon less than 1.1 x 10 per kilogram of body weight in human subjects 4 Tcon less than approximately 1.0 x 10 per kilogram of body weight in human subjects 4 Tcon less than 9.9 x 10 per kilogram of body weight in human subjects 3 Tcon less than 9.8 x 10 per kilogram of body weight in human subjects 3 Tcon less than 9.7 x 10 per kilogram of body weight in human subjects 3Tcon less than 9.6 x 10 per kilogram of body weight in human subjects 3 Tcon less than 9.5 x 10 per kilogram of body weight in human subjects 3 Tcon less than 9.4 x 10 per kilogram of body weight in human subjects 3 Tcon less than 9.3 x 10 per kilogram of body weight in human subjects 3 Tcon less than 9.2 x 10 per kilogram of body weight in human subjects 3 Tcon less than 9.1 x 10 per kilogram of body weight in human subjects 3 Tcon less than 9.0 x 10 per kilogram of body weight in human subjects 3 Tcon less than 8.9 x 10 per kilogram of body weight in human subjects 3 Tcon less than 8.8 x 10 per kilogram of body weight in human subjects 3 Tcon less than 8.7 x 10 per kilogram of body weight in human subjects 3 Tcon less than 8.6 x 10 per kilogram of body weight in human subjects 3 Tcon less than 8.5 x 10 per kilogram of body weight in human subjects 3 Tcon less than 8.4 x 10 per kilogram of body weight in human subjects 3 Tcon less than 8.3 x 10 per kilogram of body weight in human subjects 3 Tcon less than 8.2 x 10 per kilogram of body weight in human subjects 3 Tcon less than 8.1 x 10 per kilogram of body weight in human subjects 3 Tcon less than 8.0 x 10 per kilogram of body weight in human subjects 3 Tcon less than 7.9 x 10 per kilogram of body weight in human subjects 3 Tcon less than 7.8 x 10 per kilogram of body weight in human subjects 3 Tcon less than 7.7 x 10 per kilogram of body weight in human subjects 3 Tcon less than 7.6 x 10 per kilogram of body weight in human subjects 3 Tcon less than 7.5 x 10 per kilogram of body weight in human subjects 3Tcon less than 7.4 x 10 per kilogram of body weight in human subjects 3 Tcon less than 7.3 x 10 per kilogram of body weight in human subjects 3 Tcon less than 7.2 x 10 per kilogram of body weight in human subjects 3 Tcon less than 7.1 x 10 per kilogram of body weight in human subjects 3 Tcon less than 7.0 x 10 per kilogram of body weight in human subjects 3 Tcon less than 6.9 x 10 per kilogram of body weight in human subjects 3 Tcon less than 6.8 x 10 per kilogram of body weight in human subjects 3 Tcon less than 6.7 x 10 per kilogram of body weight in human subjects 3 Tcon less than 6.6 x 10 per kilogram of body weight in human subjects 3 Tcon less than 6.5 x 10 per kilogram of body weight in human subjects 3 Tcon less than 6.4 x 10 per kilogram of body weight in human subjects 3 Tcon less than 6.3 x 10 per kilogram of body weight in human subjects 3 Tcon less than 6.2 x 10 per kilogram of body weight in human subjects 3 Tcon less than 6.1 x 10 per kilogram of body weight in human subjects 3 Tcon less than 6.0 x 10 per kilogram of body weight in human subjects 3 Tcon less than 5.9 x 10 per kilogram of body weight in human subjects 3 Tcon less than 5.8 x 10 per kilogram of body weight in human subjects 3 Tcon less than 5.7 x 10 per kilogram of body weight in human subjects 3 Tcon less than 5.6 x 10 per kilogram of body weight in human subjects 3 Tcon less than approximately 5.5 x 10 per kilogram of body weight in human subjects 3 Tcon less than 5.4 x 10 per kilogram of body weight in human subjects 3 Less than 5.3 x 10 per kilogram of body weight in a human subject 3Tcon less than 5.2 x 10 per kilogram of body weight in human subjects 3 Less than 5.1 x 10 per kilogram of body weight in a human subject 3 Less than 5.0 x 10 per kilogram of body weight in a human subject 3 Tcon less than 4.9 x 10 per kilogram of body weight in human subjects 3 Tcon less than 4.8 x 10 per kilogram of body weight in human subjects 3 Tcon less than 4.7 x 10 per kilogram of body weight in human subjects 3 Tcon less than 4.6 x 10 per kilogram of body weight in human subjects 3 Less than 4.5 x 10 per kilogram of body weight in a human subject 3 Tcon less than 4.4 x 10 per kilogram of body weight in human subjects 3 Tcon less than 4.3 x 10 per kilogram of body weight in human subjects 3 Less than 4.2 x 10 per kilogram of body weight in a human subject 3 Tcon less than 4.1 x 10 per kilogram of body weight in human subjects 3 Tcon less than 4.0 x 10 per kilogram of body weight in human subjects 3 Tcon less than 3.9 x 10 per kilogram of body weight in human subjects 3 Less than 3.8 x 10 per kilogram of body weight in a human subject 3 Tcon less than 3.7 x 10 per kilogram of body weight in human subjects 3 Tcon less than 3.6 x 10 per kilogram of body weight in human subjects 3 Less than 3.5 x 10 per kilogram of body weight in a human subject 3 Tcon less than 3.4 x 10 per kilogram of body weight in human subjects 3 Less than 3.3 x 10 per kilogram of body weight in a human subject 3 Less than 3.2 x 10 per kilogram of body weight in a human subject 3 Less than 3.1 x 10 per kilogram of body weight in a human subject 3Tcon less than approximately 3.0 x 10 per kilogram of body weight in human subjects 3 Tcon less than 2.9 x 10 per kilogram of body weight in human subjects 3 Tcon less than 2.8 x 10 per kilogram of body weight in human subjects 3 Tcon less than 2.7 x 10 per kilogram of body weight in human subjects 3 Tcon less than 2.6 x 10 per kilogram of body weight in human subjects 3 Less than 2.5 x 10 per kilogram of body weight in a human subject 3 Tcon less than 2.4 x 10 per kilogram of body weight in human subjects 3 Tcon less than 2.3 x 10 per kilogram of body weight in human subjects 3 Less than 2.2 x 10 per kilogram of body weight in a human subject 3 Less than 2.1 x 10 per kilogram of body weight in a human subject 3 Less than 2.0 x 10 per kilogram of body weight in a human subject 3 Tcon less than 1.9 x 10 per kilogram of body weight in human subjects 3 Less than 1.8 x 10 per kilogram of body weight in a human subject. 3 Less than 1.7 x 10 per kilogram of body weight in a human subject. 3 Tcon less than 1.6 x 10 per kilogram of body weight in human subjects 3 Less than 1.5 x 10 per kilogram of body weight in a human subject 3 Tcon less than 1.4 x 10 per kilogram of body weight in human subjects 3 Less than 1.3 x 10 per kilogram of body weight in a human subject 3 Less than 1.2 x 10 per kilogram of body weight in a human subject 3 Tcon less than 1.1 x 10 per kilogram of body weight in human subjects 3 Less than Tcon, or approximately 1.0 × 10 per kilogram of body weight in a human subject 3 A dose of less than one Tcon is administered to the subject.

[0080] In some embodiments, the cell populations of the present disclosure, e.g., isolated CD45 + The population of cells may include one or more cells comprising one or more chimeric receptors. In some embodiments, the one or more cells may be T cells, NK cells, CTLs, Tregs, Tmems, and / or NKT cells. In some embodiments, the one or more chimeric receptors comprise one or more extracellular antigen-binding domains that bind to one or more cancer-associated antigens. Any suitable cancer-associated antigen known in the art may be targeted. In some embodiments, the chimeric receptor is a chimeric antigen receptor or a T cell receptor.

[0081] Without wishing to be bound by theory, the cell populations of the present disclosure are CD34 + The administration of a cell population comprising Treg- and Tmem-enriched HSPCs, and / or enriched in naive conventional αβ-T cells or naive conventional CD3 T cells, contributes to a favorable clinical outcome, for example, by reducing the incidence and / or severity of GVHD in transplant recipient subjects, and / or by improving immune reconstitution in transplant recipients, and / or by reducing the incidence of infection. Administration of a cell population comprising Treg- and Tmem-enriched HSPCs can facilitate the maintenance of graft-versus-tumor (GVT), reduce the incidence and / or severity of GVHD, and / or reduce the incidence and / or severity of infection. Without wishing to be bound by theory, it has been shown that Treg- and / or Tmem-enriched HSPCs, and / or enriched in naive conventional αβ-T cells or naive conventional CD3 T cells, contribute to a favorable clinical outcome, for example, by reducing the incidence and / or severity of GVHD in transplant recipient subjects, and / or by improving immune reconstitution in transplant recipients, and / or by reducing the incidence of infection. + CD25 - CD45RA +Administration of a population of T cell (Tcon)-depleted cells can prevent GVHD and / or promote GVT effects, e.g., compared to alternative hematopoietic stem cell transplant (HCT) methods, e.g., standard myeloablative allogeneic hematopoietic stem cell transplant (alloHSCT), i.e., methods different from the compositions, drug treatments, cell populations, solutions, formulations, kits, and / or methods disclosed herein. In some embodiments, administration ... compositions, drug treatments, cell populations, solutions, formulations, kits, and / or methods disclosed herein, e.g., compositions, drug treatments, cell populations, solutions, formulations, kits, and / or methods disclosed herein, e.g., compositions, drug treatments, cell populations, solutions, formulations, kits, and / or methods disclosed herein, e.g., compositions, drug treatments, cell populations, solutions, formulations, kits, and / or methods disclosed herein, e.g., compositions, drug treatments, cell populations, solutions, formulations, kits, and / or methods disclosed herein, e.g., compositions, drug treatments, cell populations, solutions, formulations, kits, and / or methods disclosed herein, e.g., compositions, drug treatments, cell populations, solutions, formulations, kits, and / or methods disclosed herein, e.g., compositions, drug treatments, cell + CD25 - CD45RA + Administration of a population of T cell (Tcon)-depleted cells promotes a GVT effect compared to alternative HCT methods, such as standard myeloablative allogeneic hematopoietic stem cell transplantation (alloHSCT), i.e., compositions, drug treatments, cell populations, solutions, formulations, kits, and / or methods different from those disclosed herein.

[0082] As used herein, an alternative composition lacks one or more cell populations and / or prophylactic agents disclosed herein. In some embodiments, the alternative composition lacks one or more cell populations including HSPCs (e.g., cell populations including Tregs) and prophylactic agents. In some embodiments, the alternative composition or treatment regimen includes an additional cell population or agent, such as, for example, an additional or different GVHD prophylactic agent, compared to the composition or treatment regimen of the present disclosure.

[0083] Cell acquisition, treatment, and preparation Certain aspects of the present disclosure relate to methods for preparing the pharmaceutical compositions, cell therapy products, cell populations, solutions, formulations, and / or kits of the present disclosure.

[0084] In some embodiments, a biological sample (e.g., a peripheral blood donation, a cord blood donation, or a bone marrow donation) is obtained from a donor (e.g., an allogeneic donor that is HLA-matched or HLA-mismatched relative to the recipient of the present disclosure) and can be sorted to isolate one or more cell populations of interest, such as one or more populations of HSPCs, one or more populations of Tregs, one or more populations of Tmems, one or more populations of iNKTs, or any combination thereof. In some cases, the biological sample of the present disclosure may be contacted with a molecule that specifically binds CD34 for the isolation of HSPCs. The sample may be contacted with a molecule that specifically binds CD34. + Enriched for cells, CD34 + Cell populations and CD34 - In some cases, CD34 - The cell population may be contacted with a molecule that specifically binds to CD25 and / or a molecule that specifically binds to 6B11. + CD34 cell population - By sorting the cell population, CD25 + and / or 6B11 + cells, thereby enriching for CD34 - CD25 - cell population or CD34 - CD25 - 6B11 - cell populations, and CD34 - CD25 + cell population or CD34 - CD25 + 6B11 + CD34 cell population. - CD25 + 6B11 + The cell population may be further sorted to give rise to Treg and iNKT cell populations. - CD25 + cells or CD34 - CD25 + 6B11 + The cells may be contacted with a molecule that specifically binds CD4 and a molecule that specifically binds CD127. The cells are then sorted to identify CD34 - CD25 +CD4 + CD127 dim / - Treg cell population or CD34 - CD25 + 6B11 + CD4 + CD127 dim / - A population of Treg cells may be obtained. In some instances, CD34 - CD25 cell population or CD34 - CD25 - The 6B11 cell population may be further sorted to enrich for Tmem cells. The cells may be contacted with a molecule that specifically binds to CD45RA. The cell sample may be sorted to enrich for CD34 - CD25 - CD45RA - Tmem cell population or CD34 - CD25 - 6B11 - CD45RA - A population of Tmem cells may be obtained. + Naive conventional αβ-T cells or naive conventional CD3 + CD25 - CD45RA + T cells (Tcon) are either naive conventional αβ-T cells or naive conventional CD3 + CD25 - CD45RA + They may be discarded for T cell (Tcon) depletion, i.e., Tcon depletion.

[0085] In some embodiments, at least one mobilized peripheral blood donation, at least two mobilized peripheral blood donations, or more mobilized peripheral blood donations are collected from a donor (e.g., an HLA-matched or HLA-mismatched allogeneic donor). In some embodiments, up to two mobilized peripheral blood donations are collected from a donor. In some embodiments, the mobilized peripheral blood donation is apheresis peripheral blood donation from which HSPCs have been mobilized. In some embodiments, prior to peripheral blood donation, the donor may be vaccinated against tumor antigens and / or pathogens to enhance graft-versus-infection.

[0086] In some embodiments, at least one bone marrow donation is collected from a donor (e.g., an HLA-matched or HLA-mismatched allogeneic donor). In some embodiments, the cell populations of the present disclosure are obtained from the bone marrow donation. In some embodiments, at least one umbilical cord blood donation is collected from a donor (e.g., an HLA-matched or HLA-mismatched allogeneic donor). In some embodiments, the cell populations of the present disclosure are obtained from the umbilical cord blood donation.

[0087] In embodiments, at least one of the mobilized peripheral blood donations, at least one of the bone marrow donations, or at least one of the umbilical cord blood donations is processed and selected to enrich for CD34+ cells, Tregs, and / or Tmems. + The processing and selection of cells, Tregs, and Tmems may be performed in any order. For example, at least one of the mobilized peripheral blood donations, at least one of the bone marrow donations, or at least one of the umbilical cord blood donations may first be purified by CD34 + Alternatively, at least one of the mobilized peripheral blood donations, at least one of the bone marrow donations, or at least one of the umbilical cord blood donations may first be treated and sorted to enrich for CD34 cells, then Tregs, and then Tmems. + Alternatively, at least one of the mobilized peripheral blood donations, at least one of the bone marrow donations, or at least one of the umbilical cord blood donations may be processed and selected to enrich for Tregs, then CD34 cells, and then Tmem cells, and then Treg cells. + Alternatively, at least one of the mobilized peripheral blood donations, at least one of the bone marrow donations, or at least one of the umbilical cord blood donations may be processed and sorted to enrich for Tregs, then Tmems, and then CD34. + Alternatively, at least one of the mobilized peripheral blood donations, at least one of the bone marrow donations, or at least one of the umbilical cord blood donations may be processed and sorted to enrich for Tmem and then CD34 cells. +Alternatively, at least one of mobilized peripheral blood donations, at least one of bone marrow donations, or at least one of umbilical cord blood donations may be processed and selected to enrich for Tmem, then Treg, and then CD34. + The cells may be treated and selected to enrich them.

[0088] In some embodiments, the processing and sorting time for at least one of the mobilized peripheral blood donations, at least one of the bone marrow donations, or at least one of the umbilical cord blood donations is less than about 40 hours; the processing and sorting time for at least one of the mobilized peripheral blood donations, at least one of the bone marrow donations, or at least one of the umbilical cord blood donations is less than about 35 hours; the processing and sorting time for at least one of the mobilized peripheral blood donations, at least one of the bone marrow donations, or at least one of the umbilical cord blood donations is less than about 30 hours; the processing and sorting time for at least one of the mobilized peripheral blood donations, at least one of the bone marrow donations, or at least one of the umbilical cord blood donations is less than about 25 hours; the processing and sorting time for at least one of the mobilized peripheral blood donations, at least one of the bone marrow donations, or at least one of the umbilical cord blood donations is less than about 20 hours; and the processing and sorting time for at least one of the mobilized peripheral blood donations, at least one of the bone marrow donations, or at least one of the umbilical cord blood donations is less than about 15 hours.

[0089] In some embodiments, the processing and sorting time for at least one of the mobilized peripheral blood donations, at least one of the bone marrow donations, or at least one of the umbilical cord blood donations is up to about 35 hours; the processing and sorting time for at least one of the mobilized peripheral blood donations, at least one of the bone marrow donations, or at least one of the umbilical cord blood donations is up to about 30 hours; the processing and sorting time for at least one of the mobilized peripheral blood donations, at least one of the bone marrow donations, or at least one of the umbilical cord blood donations is up to about 25 hours; the processing and sorting time for at least one of the mobilized peripheral blood donations, at least one of the bone marrow donations, or at least one of the umbilical cord blood donations is up to about 20 hours; or the processing and sorting time for at least one of the mobilized peripheral blood donations, at least one of the bone marrow donations, or at least one of the umbilical cord blood donations is up to about 15 hours.

[0090] In some embodiments, the cell populations of the present disclosure (e.g., isolated CD45 +The cell populations of the present disclosure can be obtained from a peripheral blood apheresis product, such as a mobilized peripheral blood apheresis product, mobilized by administering one or more mobilizing agents to a donor. Non-limiting examples of mobilizing agents include granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), stem cell factor (SCF), SDF-1 antagonists, CXCR4 antagonists (e.g., POL6326, BKT-140, TG-0054, NOX-A12), Mozovir® (plelixafor), CXCR2 ligands (e.g., GROβ), sphingosine-1-phosphatase (S1P) agonists (e.g., SEW2871), VCAM / VLA-4 inhibitors (e.g., BIO5192), proteosome inhibitors (e.g., bortezomib), parathyroid hormone, hypoxia-inducible factor (HIF) stabilizers (e.g., FG-4497), and combinations thereof. Techniques for mobilizing stem cells into peripheral blood can include administering a mobilization agent to the donor at a dose of 10-40 μg / kg / day. The mobilization agent can be administered to the donor in, for example, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 doses. The apheresis product can be isolated from the donor approximately 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 26, 28, or 30 hours after administration of the mobilization agent.

[0091] The cell populations of the present disclosure can be obtained from at least one apheresis product, two apheresis products, three apheresis products, four apheresis products, five apheresis products, six apheresis products, or more. In some embodiments, the cell populations of the present disclosure are obtained from one apheresis product. In some embodiments, the cell populations of the present disclosure are obtained from two apheresis products. In some embodiments, the cell populations of the present disclosure are obtained from an apheresis product from one donor and an apheresis product from at least a second donor. In some embodiments, the cell populations of the present disclosure can be obtained from two or more apheresis products obtained from a donor on different days. In some embodiments, a bone marrow stimulating agent (e.g., 0.24 mg / kg plerixafor subcutaneously) can be administered to the donor after the first apheresis and before subsequent apheresis.

[0092] The cell populations of the present disclosure can be purified by selection from a cell population, such as, for example, peripheral blood or peripheral blood apheresis products, bone marrow, or umbilical cord blood. Cell population selection methods can include methods involving positive or negative selection of the desired cell population. Cell population selection methods can include affinity reagents, including, but not limited to, antibodies, full-length antibodies, antibody fragments, naturally occurring antibodies, synthetic antibodies, engineered antibodies, full-length affibodies, affibody fragments, full-length affilins, affilin fragments, full-length anticalins, anticalin fragments, full-length avimers, avimer fragments, full-length DARPins, DARPin fragments, full-length finomers, finomer fragments, full-length kunitz domain peptides, kunitz domain peptide fragments, full-length monobodies, monobody fragments, peptides, or polyamino acids. In some embodiments, the affinity reagent is directly conjugated to the detection reagent and / or purification reagent. In some cases, the detection reagent and the purification reagent are the same. In some cases, the detection reagent and the purification reagent are different. For example, the detection reagent and / or purification reagent is a fluorescent, magnetic, etc. reagent. In some cases, the detection reagent and / or purification reagent is a magnetic particle for column purification. For example, magnetic column purification can be performed using the columns, antibodies, buffers, preparation materials and reagents of the Miltenyi system (CliniMAC).

[0093] Affinity reagents include immunoaffinity reagents that utilize the binding specificity of antibodies or their fragments or derivatives to positively or negatively select cell populations of interest. Cell population selection methods can include affinity agents and columns, such as magnetic-activated cell sorting (MACS) using specific antibodies and microbeads. Cell population selection methods can include fluorescence-activated cell sorting (FACS), in which cell populations are sorted based on their staining profile using one or more fluorescently conjugated antibodies. Cell population selection methods can include physical adsorption, e.g., physical adsorption of T cells to a protein ligand such as a lectin.

[0094] The number of cells in various cell populations provided herein can be determined, for example, by quantifying cell determinants through flow cytometry.In some embodiments, dosage calculation is adjusted based on the measurement of cell viability, for example, the viability determined by flow cytometry using propidium iodide or 7-AAD or by trypan blue exclusion.

[0095] In various embodiments, at least one of the mobilized peripheral blood donations, at least one of the bone marrow donations, and / or at least one of the umbilical cord blood donations is processed and sorted using one or more immunoseparation particles (ISPs), e.g., the ISPs include affinity reagents, such as immunomagnetic separation particles, which may each be an antibody bound to an iron-containing particle. In some embodiments, the affinity reagents include multiple CD34 reagents (e.g., anti-CD34 antibodies) that bind to one or more CD34 receptors on HSPCs.

[0096] In some cases, at least some of the plurality of ISPs bind to CD34+ receptors on HSPCs in the HSPC cell population, and optionally, the average number of ISPs per HSPC in the HSPC cell population is less than about 20,000, the average number of ISPs per HSPC in the HSPC cell population is equal to or less than about 10,000, and / or the average number of ISPs per HSPC in the HSPC cell population is between about 1,000 and about 20,000.

[0097] In some embodiments, the average number of ISPs per HSPC in the HSPC cell population may be about 1,500 to about 20,000. In some embodiments, the average number of ISPs per HSPC in the HSPC cell population may be at least about 1,500. In some embodiments, the average number of ISPs per HSPC in the HSPC cell population may be up to about 20,000. In some embodiments, the average number of ISPs per HSPC in the HSPC cell population is about 1,500 to about 2,000, about 1,500 to about 5,000, about 1,500 to about 6,000, about 1,500 to about 10,000, about 1,500 to about 12,000, about 1,500 to about 15,000, about 1,500 to about 20,000, about 2,000 to about 5,000, about 2,000 to about 6,000, about 2,000 to about 10,000, about 2,000 to about 12,000, about 2,000 to about 15,000, about 2,000 to about 20,000, or about 5,000. It may be about 6,000 to about 6,000, about 5,000 to about 10,000, about 5,000 to about 12,000, about 5,000 to about 15,000, about 5,000 to about 20,000, about 6,000 to about 10,000, about 6,000 to about 12,000, about 6,000 to about 15,000, about 6,000 to about 20,000, about 10,000 to about 12,000, about 10,000 to about 15,000, about 10,000 to about 20,000, about 12,000 to about 15,000, about 12,000 to about 20,000, or about 15,000 to about 20,000. In some embodiments, the average number of ISPs per HSPC in the HSPC cell population may be about 1,500, about 2,000, about 5,000, about 6,000, about 10,000, about 12,000, about 15,000, or about 20,000. In some embodiments, the average number of ISPs per HSPC in the HSPC cell population may be at least 1,500, 2,000, 5,000, 6,000, 10,000, 12,000, 15,000, or 20,000. In some embodiments, the average number of ISPs per HSPC in the HSPC cell population may be up to 1,500, 2,000, 5,000, 6,000, 10,000, 12,000, 15,000, or 20,000.

[0098] In some cases, at least a portion of the plurality of ISPs bind to CD25+ receptors on cells of the Treg cell population, and optionally, the average number of ISPs per T-reg cell in the Treg population is equal to or less than about 4000, or the average number of ISPs per T-reg cell in the Treg population is between about 1500 and about 2500. In some cases, at least a portion of the plurality of ISPs bind to CD3+ receptors on cells of the heterogeneous cell population, and optionally, the average number of ISPs per cell in the T heterogeneous population is less than about 4,000.

[0099] In some embodiments, the average number of ISPs per Treg cell in a Treg cell population may be about 500 to about 4,000. In some embodiments, the average number of ISPs per Treg cell in a Treg cell population may be at least about 500. In some embodiments, the average number of ISPs per Treg cell in a Treg cell population may be up to about 4,000. In some embodiments, the average number of ISPs per Treg cell in a Treg cell population is about 500 to about 1,000, about 500 to about 1,500, about 500 to about 2,000, about 500 to about 2,500, about 500 to about 3,000, about 500 to about 4,000, about 1,000 to about 1,500, about 1,000 to about 2,000, about 1,000 to about 2,500, or about 1,000 to about 3,000. In some embodiments, the average number of ISPs per Treg cell in the Treg cell population may be about 500, about 1,000, about 1,500, about 2,000, about 2,500, about 3,000, about 4,000, about 1,000 to about 4,000, about 1,500 to about 2,000, about 1,500 to about 2,500, about 1,500 to about 3,000, about 1,500 to about 4,000, about 2,000 to about 2,500, about 2,000 to about 3,000, about 2,000 to about 4,000, about 2,500 to about 3,000, about 2,500 to about 4,000, or about 3,000 to about 4,000. In some embodiments, the average number of ISPs per Treg cell in the Treg cell population may be at least 500, 1,000, 1,500, 2,000, 2,500, 3,000, or 4,000. In some embodiments, the average number of ISPs per Treg cell in the Treg cell population may be up to 500, 1,000, 1,500, 2,000, 2,500, 3,000, or 4,000.

[0100] The cell population of the present disclosure may be enriched for Tregs. Tregs can be selected based on the expression of markers including CD3, CD4, CD25, CD127, FOXP3, and combinations thereof. Tregs may be isolated from whole blood. Tregs can be isolated from peripheral blood apheresis products, bone marrow, and / or umbilical cord blood. Tregs may be isolated from a population of cells previously enriched and / or depleted of one or more other cell types, for example, from a population of cells depleted of CD34+ cells. In some embodiments, Tregs are isolated from the flow-through fraction of CD34+ MACS selection. The number of Tregs in a population of cells can be determined, for example, by flow cytometry, and Tregs can be identified as, for example, CD4+CD25+CD127dim or CD4+FOXP3+. Dose calculations can be adjusted based on measures of cell viability, for example, viability determined by flow cytometry using propidium iodide or 7-AAD, or trypan blue dye exclusion.

[0101] The cell population of the present disclosure may include a population of Tmem. The population of Tmem can be obtained from peripheral blood, bone marrow, and / or umbilical cord blood. The population of Tmem can be sourced from peripheral blood apheresis products. The population of cells can be enriched for Tmem by sorting based on the expression of various markers, for example, using MACS, FACS, or a combination thereof. The population of Tmem can be enriched by sorting, for example, CD3+CD45RA-CD45RO+ cells. The number of Tmem present in the population can be quantified, for example, by quantifying CD3+CD45RA-CD45RO+ cells by flow cytometry. The number of CD3+CD45RA-CD45RO+ cells in an aliquot can be determined to determine the volume containing the appropriate dose of Tmem to be administered to the recipient. Dose calculations can be adjusted based on a measure of cell viability, for example, viability determined by flow cytometry using propidium iodide or 7-AAD, or trypan blue dye exclusion.

[0102] The cell population of the present disclosure may include a population of iNKT. The iNKT population can be obtained from peripheral blood, bone marrow, and / or umbilical cord blood. The iNKT population can be sourced from peripheral blood apheresis products. The cell population can be enriched for iNKT by sorting based on the expression of various markers, for example, using MACS, FACS, or a combination thereof. The iNKT population can be enriched, for example, by sorting for CD3+Vα24Jα18+ cells. The number of iNKT cells present in the population can be quantified, for example, by quantifying CD3+Vα24Jα18+ cells by flow cytometry. The number of CD3+Vα24Jα18+ cells in an aliquot can be determined to determine the volume containing the appropriate dose of iNKT to be administered to the recipient. In some embodiments, dose calculations are adjusted based on a measure of cell viability, for example, viability determined by flow cytometry using propidium iodide or 7-AAD, or by trypan blue exclusion.

[0103] The cell populations of the present disclosure may be naive conventional αβ-T cells or naive conventional CD3 + CD25 - CD45RA + The T cells (Tcon) may lack or have reduced amounts. In some embodiments, the Tcon is CD45RA + These cells were discarded and replaced with naive conventional αβ-T cells or naive conventional CD3 + CD25 - CD45RA + This may result in depletion of T cells (Tcon).

[0104] The cell populations of the present disclosure can be administered fresh after isolation. Freshly isolated cells from a donor ("fresh cells") can be administered to a recipient subject. Fresh cells can be stored in a buffer, such as CliniMACs PBS-EDTA buffer containing 0.5% human serum albumin, or Plasma-Lyte-A, pH 7.4, supplemented with 2% human serum albumin. Fresh cells can be stored at low temperatures (e.g., 2-8°C) with or without cryopreservation.

[0105] After obtaining the population of fresh cells from the donor, the fresh cells may be incubated for at least about 1 hour, at least about 2 hours, at least about 3 hours, at least about 4 hours, at least about 5 hours, at least about 6 hours, at least about 7 hours, at least about 8 hours, at least about 9 hours, at least about 10 hours, at least about 11 hours, at least about 12 hours, at least about 13 hours, at least about 14 hours, at least about 15 hours, at least about 16 hours, at least about 17 hours, at least about 18 hours, at least about 19 hours, at least about 20 hours, at least about 21 hours, at least about 22 hours, at least about 23 hours, at least about 24 hours, at least about 25 hours, at least about 26 hours, at least about 27 hours, at least about 28 hours, at least about 29 hours, at least about 30 hours, at least about 31 hours, at least about 32 hours, at least about 33 hours, at least about 34 hours, at least about 35 hours, at least about 36 hours, at least about 37 hours, at least about 38 hours, at least about 39 hours, at least about 40 hours, at least about 41 hours, at least about 42 hours, at least about 43 hours, at least about 44 hours, at least about 45 hours, at least about 46 hours, at least about 47 hours, at least about 48 hours, at least about 49 hours, at least about 50 hours, at least about 51 hours, at least about 52 hours, at least about 53 hours, at least about 54 hours, at least about 55 hours, at least about 56 hours, at least about 57 hours, at least about 58 hours, at least about 59 hours, at least about 60 hours, at least about 61 hours, at least about 62 hours, at least about 6 and may be stored for at least about 29 hours, at least about 30 hours, at least about 31 hours, at least about 32 hours, at least about 33 hours, at least about 34 hours, at least about 35 hours, at least about 36 hours, at least about 37 hours, at least about 38 hours, at least about 39 hours, at least about 40 hours, at least about 44 hours, at least about 48 hours, at least about 50 hours, at least about 55 hours, at least about 60 hours, at least about 61 hours, at least about 62 hours, at least about 65 hours, at least about 70 hours, at least about 72 hours, at least about 80 hours, at least about 90 hours, at least about 96 hours, at least about 120 hours, at least about 150 hours, at least about 200 hours, at least about 300 hours, or longer.

[0106] After the population of fresh cells is obtained from a donor, the fresh cells may be stored for up to about 1 hour, up to about 2 hours, up to about 3 hours, up to about 4 hours, up to about 5 hours, up to about 6 hours, up to about 7 hours, up to about 8 hours, up to about 9 hours, up to about 10 hours, up to about 12 hours, up to about 14 hours, up to about 16 hours, up to about 18 hours, up to about 20, up to about 22 hours, up to about 24 hours, up to about 30 hours, up to about 36 hours, up to about 40 hours, up to about 48 hours, up to about 60 hours, up to about 70 hours, up to about 72 hours, up to about 80 hours, up to about 90 hours, up to about 96 hours, up to about 120 hours, up to about 150 hours, up to about 200 hours, or up to about 300 hours before administration to a subject.

[0107] In some embodiments, after treatment, one or more cell populations of the present disclosure (e.g., isolated CD45 +The population of cells may be formulated with one or more excipients. In some embodiments, the one or more excipients include a buffer, such as a transport buffer or an infusion buffer. In some embodiments, the cell population is formulated at a neutral pH. In some embodiments, the population of HSPCs, or at least one dose of HSPCs, of the present disclosure is formulated with one or more excipients at a neutral pH. In some embodiments, the population of Tregs, or at least one dose of Tregs, of the present disclosure is formulated with one or more excipients at a neutral pH. In some embodiments, the population of Tmems, or at least one dose of Tmems, of the present disclosure is formulated with one or more excipients at a neutral pH. In some embodiments, the population of iNKTs, or at least one dose of iNKTs, of the present disclosure is formulated with one or more excipients at a neutral pH. In some embodiments, the population or dose of HSPCs and the population or dose of Tregs of the present disclosure are formulated with one or more excipients at a neutral pH. In some embodiments, the population or dose of HSPCs and the population or dose of Tmem of the present disclosure are formulated with one or more excipients at a neutral pH. In some embodiments, the population or dose of HSPCs and the population or dose of iNKT of the present disclosure are formulated with one or more excipients at a neutral pH. In some embodiments, the population or dose of Tregs and the population or dose of Tmem of the present disclosure are formulated with one or more excipients at a neutral pH. In some embodiments, the population or dose of Tregs and the population or dose of iNKT of the present disclosure are formulated with one or more excipients at a neutral pH. In some embodiments, the population or dose of Tmem and the population or dose of iNKT of the present disclosure are formulated with one or more excipients at a neutral pH. In some embodiments, the population or dose of HSPCs, the population or dose of Tregs, and the population or dose of Tmem of the present disclosure are formulated with one or more excipients at a neutral pH. In some embodiments, the populations or doses of HSPCs, populations or doses of Tregs, and populations or doses of iNKTs of the present disclosure are formulated with one or more excipients at a neutral pH. In some embodiments, the populations or doses of HSPCs, populations or doses of Tmems, and populations or doses of iNKTs of the present disclosure are formulated with one or more excipients at a neutral pH.In some embodiments, the populations or doses of Tregs, populations or doses of Tmems, and populations or doses of iNKTs of the present disclosure are formulated with one or more excipients at a neutral pH. In some embodiments, the populations or doses of HSPCs, populations or doses of Tregs, populations or doses of Tmems, and populations or doses of iNKTs of the present disclosure are formulated with one or more excipients at a neutral pH. In some embodiments, the one or more excipients comprise one or more transport buffers.

[0108] In some embodiments, the neutral pH ranges from about 6.8 to about 7.6. In some embodiments, the neutral pH is about 6.8, about 6.85, about 6.9, about 6.95, about 7, about 7.05, about 7.1, about 7.15, about 7.2, about 7.25, about 7.3, about 7.35, about 7.4, about 7.45, about 7.5, about 7.55, or about 7.6.

[0109] In some embodiments, one or more cell populations of the present disclosure (e.g., isolated CD45 + The cell population may be formulated in one or more excipients. In some embodiments, the one or more excipients may include one or more buffers. The buffer may be a transport buffer or an infusion buffer. Transport buffers suitable for use with the cell population of the present disclosure include buffers having milliequivalents (mEq) of sodium ranging from about 120 mEq sodium to about 160 mEq sodium. In some embodiments, the transport buffer of the present disclosure includes about 120 mEq sodium, about 125 mEq sodium, about 130 mEq sodium, about 135 mEq sodium, about 140 mEq sodium, about 145 mEq sodium, about 120 mEq sodium, about 150 mEq sodium, about 155 mEq sodium, or about 160 mEq sodium.

[0110] Transport buffers suitable for use with the cell populations of the present disclosure include buffers having an osmolality ranging from about 270 mOsmol / L to about 320 mOsmol / L. In some embodiments, transport buffers of the present disclosure have an osmolality of about 270 mOsmol / L, about 275 mOsmol / L, about 280 mOsmol / L, about 285 mOsmol / L, about 290 mOsmol / L, about 295 mOsmol / L, about 300 mOsmol / L, about 305 mOsmol / L, about 310 mOsmol / L, about 315 mOsmol / L, or about 320 mOsmol / L.

[0111] In some embodiments, one or more cell populations of the present disclosure (e.g., isolated CD45 + Suitable transport buffers for use with one or more cell populations (e.g., isolated CD45 cells) of the present disclosure include, but are not limited to, phosphate buffered saline (PBS), human serum, Plasmalyte, and any combination thereof. In some embodiments, one or more cell populations (e.g., isolated CD45 cells) of the present disclosure may be used. + In some embodiments, one or more cell populations of the present disclosure (e.g., isolated CD45 + In some embodiments, one or more cell populations of the present disclosure (e.g., isolated CD45 + In some embodiments, one or more cell populations of the present disclosure (e.g., isolated CD45 + The cell population is formulated with a sufficient amount of Plasmalyte (e.g., Plasmalyte A).

[0112] In some embodiments, the transport buffer of the present disclosure may further comprise a human carrier protein, including, but not limited to, human serum albumin (HSA), intravenous immunoglobulin (IVIG), AB serum, or any combination thereof. In some embodiments, the human carrier protein has a concentration of human carrier protein ranging from about 0.1% w / v to about 10% w / v.In some embodiments, the human carrier protein is about 0.1% w / v, about 0.2% w / v, about 0.3% w / v, about 0.4% w / v, about 0.5% w / v, about 0.6% w / v, about 0.7% w / v, about 0.8% w / v, about 0.9% w / v, about 1.0% w / v, about 1.1% w / v, about 1.2% w / v, about 1.3% w / v, about 1.4% w / v, about 1.5% w / v, about 1.6% w / v, about 1.7% w / v, about 1.8% w / v, about 1.9% w / v, about 2.0% w / v, about 2.1% w / v, about 2.2% w / v, about 2.3% w / v, about 2.4% w / v / v, approx. 2.5%w / v, approx. 2.6%w / v, approx. 2.7%w / v, approx. 2.8%w / v, approx. 2.9%w / v, approx. 3.0%w / v, approx. 3 .1%w / v, approx. 3.2%w / v, approx. 3.3%w / v, approx. 3.4%w / v, approx. 3.5%w / v, approx. 3.6%w / v, approx. 3.7%w / v, approx. 3.8%w / v, approx. 3.9%w / v, approx. 4.0%w / v, approx. 4.1%w / v, approx. 4.2%w / v, approx. 4.3%w / v, approx. 4. 4%w / v, approx. 4.5%w / v, approx. 4.6%w / v, approx. 4.7%w / v, approx. 4.8%w / v, approx. 4.9%w / v, approx. 5.0%w / v , approx. 5.1%w / v, approx. 5.2%w / v, approx. 5.3%w / v, approx. 5.4%w / v, approx. 5.5%w / v, approx. 5.6%w / v, approx. 5.7 %w / v, approx. 5.8%w / v, approx. 5.9%w / v, approx. 6.0%w / v, approx. 6.1%w / v, approx. 6.2%w / v, approx. 6.3%w / v, Approx. 6.4%w / v, approx. 6.5%w / v, approx. 6.6%w / v, approx. 6.7%w / v, approx. 6.8%w / v, approx. 6.9%w / v, approx. 7.0% w / v, approx. 7.1%w / v, approx. 7.2%w / v, approx. 7.3%w / v, approx. 7.4%w / v, approx. 7.5%w / v, approx. 7.6%w / v, approx. and having a concentration of human carrier protein of 7.7% w / v, about 7.8% w / v, about 7.9% w / v, about 8.0% w / v, about 8.1% w / v, about 8.2% w / v, about 8.3% w / v, about 8.4% w / v, about 8.5% w / v, about 8.6% w / v, about 8.7% w / v, about 8.8% w / v, about 8.9% w / v, about 9.0% w / v, about 9.1% w / v, about 9.2% w / v, about 9.3% w / v, about 9.4% w / v, about 9.5% w / v, about 9.6% w / v, about 9.7% w / v, about 9.8% w / v, about 9.9% w / v, or about 10% w / v.

[0113] In some embodiments, one or more cell populations of the present disclosure (e.g., isolated CD45 +The population of cells (e.g., with one or more excipients, such as a transport buffer, of the present disclosure) is formulated in a quantity sufficient to obtain a volume ranging from about 5 mL to 1 L. In some embodiments, the population of cells (e.g., with one or more excipients, such as a transport buffer) is formulated in a quantity sufficient to obtain a volume ranging from about 5 mL to 1 L. In some embodiments, the population of cells (e.g., with one or more excipients, such as a transport buffer) is formulated in a quantity sufficient to obtain a volume ranging from about 5 mL to 1 L. In some embodiments, the population of cells (e.g., with one or more excipients, such as a transport buffer) is formulated in a quantity sufficient to obtain a volume ranging from about 5 mL to 1 L. 145mL, about 150mL, about 155mL, about 160mL, about 165mL, about 170mL, about 175mL, about 180mL, about 185mL, about 190mL, about 195mL, about 200mL, about 205mL, about 210mL, about 215mL, about 220m L, about 225mL, about 230mL, about 235mL, about 240mL, about 245mL, about 250mL, about 255mL, about 260mL, about 265mL, about 270mL, about 275mL, about 280mL, about 285mL, about 290mL, about 295mL, about 30 0mL, about 305mL, about 310mL, about 315mL, about 320mL, about 325mL, about 330mL, about 335mL, about 340mL, about 345mL, about 350mL, about 355mL, about 360mL, about 365mL, about 370mL, about 375mL, 380mL, 385mL, 390mL, 395mL, 400mL, 405mL, 410mL, 415mL, 420mL, 425mL, 430mL, 435mL, 440mL, 445mL, 450mL, 455m L, about 460mL, about 465mL, about 470mL, about 475mL, about 480mL, about 485mL, about 490mL, about 495mL, about 500mL, about 505mL, about 510mL, about 515mL, about 520mL, about 525mL, about 530mL, about 5 35mL, approx. 540mL, approx. 545mL, approx. 550mL, approx. 555mL, approx. 560mL, approx. 565mL, approx. 570mL, approx. 575mL, approx.Approx. 615mL, approx. 620mL, approx. 625mL, approx. 630mL, approx. 635mL, approx. 640mL, approx. 645mL, approx. 650mL, approx. 655mL, approx. 660mL , about 665mL, about 670mL, about 675mL, about 680mL, about 685mL, about 690mL, about 695mL, about 700mL, about 705mL, about 710mL , about 715mL, about 720mL, about 725mL, about 730mL, about 735mL, about 740mL, about 745mL, about 750mL, about 755mL, about 760m L, approximately 765mL, approximately 770mL, approximately 775mL, approximately 780mL, approximately 785mL, approximately 790mL, approximately 795mL, approximately 800mL, approximately 805mL, approximately 810m L, about 815 mL, about 820 mL, about 825 mL, about 830 mL, about 835 mL, about 840 mL, about 845 mL, about 850 mL, about 855 mL, about 860 mL, about 865 mL, about 870 mL, about 875 mL, about 880 mL, about 885 mL, about 890 mL, about 895 mL, about 900 mL, about 905 mL, about 910 mL, about 915 mL, about 920 mL, about 925 mL, about 930 mL, about 935 mL, about 940 mL, about 945 mL, about 950 mL, about 955 mL, about 960 mL, about 965 mL, about 970 mL, about 975 mL, about 980 mL, about 985 mL, about 990 mL, about 995 mL, or about 1 L. In some embodiments, the formulations of the present disclosure further comprise a human carrier protein of the present disclosure. In some embodiments, the formulations of the present disclosure further comprise one or more cryoprotectants.

[0114] The cell populations of the present disclosure (e.g., isolated CD45 +The cells (populations of cells) can be cryopreserved. In some embodiments, cryopreservation can be beneficial for the methods disclosed herein. Cryopreservation can include the addition of a preservative (e.g., DMSO) or one or more cryoprotectants, and can involve gradually cooling the cells in a controlled-rate freezer to prevent cell damage due to osmotic pressure resulting from ice crystal formation. Cryopreservation can include commercially available cryopreservation reagents and materials (e.g., cryoprotectants), such as Cryobags sorbitol, dimethyl sulfoxide (DMSO), propylene glycol, glycerol, polyvinylpyrrolidone (PVP), and polyethylene glycol (PEG), serum, HSA, hetastarch, CRYOSTOR CS2, CRYOSTOR CS5, and CRYOSTOR CS10. In certain embodiments, the cryoprotectant of the present disclosure includes DMSO. For example, in some embodiments, the population of cells can be formulated for cryopreservation using a cryoprotectant comprising DMSO in an amount ranging from about 1% v / v to about 15% v / v. Cryopreserved cells can be stored at low temperatures for periods ranging from a few hours to several years. Cryopreserved cells can be stored at ultra-low temperatures, such as -50°C, -60°C, -70°C, -80°C, -90°C, -100°C, -110°C, -120°C, -130°C, -140°C, -150°C, -160°C, -170°C, -180°C, -190°C, -196°C, or lower. Cryopreserved cells can be stored in a storage device containing liquid nitrogen. Cells can be cryopreserved before or after certain steps of the disclosed methods, such as before or after a sorting step, or before or after a characterization step, such as determining cell viability or concentration of a particular cell type.

[0115] In some embodiments, once formulated, one or more cell populations of the present disclosure (e.g., isolated CD45 + The cell populations of the present disclosure may be placed in one or more containers. In certain aspects, the present disclosure provides for the preparation of one or more cell populations of the present disclosure (e.g., isolated CD45 +The present invention relates to a system comprising one or more containers containing a population of cells (e.g., isolated CD45 cells). In some embodiments, the one or more containers are filled to an appropriate volume (e.g., 5 mL to 1 L) with one or more excipients of the present disclosure, e.g., one or more transport buffers, one or more human carrier proteins, and / or one or more cryoprotectants, at an appropriate pH, e.g., neutral pH. In some embodiments, a single container contains a population of cells (e.g., isolated CD45 cells). + In some embodiments, the container of the present disclosure includes, but is not limited to, a vial, a syringe, a bag (e.g., a transfer bag), a cryoprotectant container, and any combination thereof. In some embodiments, the container is a bag, such as a transfer bag that can be used for intravenous infusion. In some embodiments, the transfer bag of the present disclosure is a single-dose transfer bag. In some embodiments, the transfer bag of the present disclosure is a polyvinyl chloride (PVC) transfer bag or an ethylene vinyl acetate (EVA) transfer bag.

[0116] Certain aspects of the present disclosure relate to systems, such as cell therapy or treatment systems, that include one or more of the containers of the present disclosure. Other aspects of the present disclosure relate to articles of manufacture that include one or more of the containers of the present disclosure. Other aspects of the present disclosure relate to kits that include one or more of the containers of the present disclosure.

[0117] donor 1.General information Human leukocyte antigens (HLA), also broadly referred to as major histocompatibility complex (MHC) antigens, are protein molecules expressed on the cell surface that can confer antigenic identity to that cell. HLA / MHC antigens are target molecules that can be recognized by T cells and natural killer (NK) cells as either derived from the same hematopoietic stem cell source as immune effector cells ("self") or from a different hematopoietic cell source ("non-self"). HLA class I antigens (A, B, and C in humans) are expressed by the majority of cells, whereas HLA class II antigens (DR, DP, and DQ in humans) are primarily expressed by professional antigen-presenting cells. Both HLA classes can be involved in GVHD.

[0118] HLA antigens are encoded by highly polymorphic genes, and various alleles exist for each HLA class I and II gene. The gene products of the alleles may differ by one or more amino acids in the α and / or β domains. A panel of specific antibodies or nucleic acid reagents can be used to determine an individual's HLA haplotype, for example, using white blood cells expressing class I and class II molecules. HLA alleles can be described at various levels. Most nomenclatures begin with the HLA and locus name, followed by several (even-numbered) digits that identify the allele. The first two digits may identify a group of alleles. The third or fourth digit, if present, may identify synonymous alleles. The fifth or sixth digit, if present, may indicate any synonymous mutation within the coding frame of the gene. The seventh or eighth digit, if present, may identify a mutation outside the coding region. A letter, such as L, N, Q, or S, follows the allele name and identifies the expression level or other non-genomic data known in this context. Thus, a fully described allele may be up to 9 alleles in length, not including the HLA prefix and locus designation.

[0119] A set of HLA alleles inherited from one parent forms a haplotype.HLA half-matching can refer to a donor-recipient pair in which one chromosome is matched between donor and recipient at least in HLA-A, HLA-B, and HLA-DR.A half-matching pair may or may not match in other alleles, such as other HLA genes on other chromosomes, or additional histocompatibility loci on either chromosome.Such donors often exist within families; for example, parents may be half-matched to their children, and siblings may also be half-matched.

[0120] The cell population can be derived from a donor that has been HLA-typed for any number of HLA alleles. The donor and recipient can be HLA-matched, e.g., matched for all typed HLA alleles. The donor and recipient can also be HLA-mismatched, e.g., at least one HLA antigen can be mismatched between the donor and recipient.

[0121] In some embodiments, a related or unrelated donor and subject may be HLA-typed for six alleles, consisting of HLA-A, HLA-B, and HLA-DR alleles. The donor and subject may be, for example, 3 / 6, 4 / 6, 5 / 6, or 6 / 6 allele-matched. In some embodiments, the donor and subject are matched for at least 5 / 6 alleles. In some embodiments, the donor and subject are matched for 6 / 6 alleles.

[0122] In some embodiments, a related or unrelated donor and subject may be HLA-typed for eight alleles, consisting of HLA-A, HLA-B, HLA-C, and HLA-DR alleles (e.g., the HLA-DRB1 allele). The donor and subject may be matched, for example, at 4 / 8, 5 / 8, 6 / 8, 7 / 8, or 8 / 8 alleles. In some embodiments, the donor and subject are matched at least 6 / 8 alleles. In some embodiments, the donor and subject are matched at least 7 / 8 alleles. In some embodiments, the donor and subject are matched at 8 / 8 alleles.

[0123] In some embodiments, a related or unrelated donor and subject may be HLA-typed for ten alleles consisting of HLA-A, HLA-B, HLA-C, and HLA-DR alleles (e.g., the HLA-DRB1 allele). The donor and subject may be matched, for example, at 5 / 10, 6 / 10, 7 / 10, 8 / 10, 9 / 10, or 10 / 10 alleles. In some embodiments, the donor and subject are matched for at least 7 / 10 alleles. In some embodiments, the donor and subject are matched for at least 8 / 10 alleles. In some embodiments, the donor and subject are matched for at least 9 / 10 alleles. In some embodiments, the donor and subject are matched for 10 / 10 alleles.

[0124] In some embodiments, a related or unrelated donor and subject may be HLA-typed at 12 alleles, e.g., HLA-A, HLA-B, HLA-C, HLA-DR alleles (e.g., HLA-DRB1 allele), and HLA-DP alleles (e.g., HLA-DPB1 allele). The donor and subject may be matched at, for example, 6 / 12, 7 / 12, 8 / 12, 9 / 12, 10 / 12, 11 / 12, or 12 / 12 alleles. In some embodiments, the donor and subject are matched at at least 9 / 12 alleles. In some embodiments, the donor and subject are matched at at least 10 / 12 alleles. In some embodiments, the donor and subject are matched at at least 11 / 12 alleles. In some embodiments, the donor and subject are matched at 12 / 12 alleles.

[0125] The cell population may be generated from a matched unrelated donor that is 8 / 8 matched for HLA-A, -B, -C, and -DRB1, all of which are typed using high-throughput DNA-based methods. The cell population may be generated from a matched unrelated donor that is 7 / 8 matched for HLA-A, -B, -C, and -DRB1, all of which are typed using high-throughput DNA-based methods. The cell population may be generated from a matched unrelated donor that is 6 / 8 matched for HLA-A, -B, -C, and -DRB1, all of which are typed using high-throughput DNA-based methods. The cell population may be generated from a matched unrelated donor that is 10 / 10 matched for HLA-A, -B, -C, -DQB1, and -DRB1, all of which are typed using high-throughput DNA-based methods. The cell population may be generated from a matched unrelated donor that is a 9 / 10 match for HLA-A, -B, -C, -DQB1, and -DRB1, all of which are typed using high-throughput DNA-based methods. The cell population may be generated from a matched unrelated donor that is an 8 / 10 match for HLA-A, -B, -C, -DQB1, and -DRB1, all of which are typed using high-throughput DNA-based methods. The cell population may be generated from a matched unrelated donor that is a 7 / 10 match for HLA-A, -B, -C, -DQB1, and -DRB1, all of which are typed using high-throughput DNA-based methods. The cell population may be generated from a matched unrelated donor who is 12 / 12 matched for HLA-A, -B, -C, -DQB1, -DRB1, and DPB1, all of which are typed using high-throughput DNA-based methods. The cell population may be generated from a matched unrelated donor who is 11 / 12 matched for HLA-A, -B, -C, -DQB1, -DRB1, and DPB1, all of which are typed using high-throughput DNA-based methods. The cell population may be generated from a matched unrelated donor who is 10 / 12 matched for HLA-A, -B, -C, -DQB1, -DRB1, and DPB1, all of which are typed using high-throughput DNA-based methods.Cell populations may be generated from matched unrelated donors who are 9 / 12 matched for HLA-A, -B, -C, -DQB1, -DRB1, and DPB1, all of which are typed using high-throughput DNA-based methods.

[0126] The cell population may be generated from a matched related donor that is 8 / 8 matched for HLA-A, -B, -C, and -DRB1, all of which are typed using high-throughput DNA-based methods. The cell population may be generated from a matched related donor that is 7 / 8 matched for HLA-A, -B, -C, and -DRB1, all of which are typed using high-throughput DNA-based methods. The cell population may be generated from a matched related donor that is 6 / 8 matched for HLA-A, -B, -C, and -DRB1, all of which are typed using high-throughput DNA-based methods. The cell population may be generated from a matched related donor that is 10 / 10 matched for HLA-A, -B, -C, -DQB1, and -DRB1, all of which are typed using high-throughput DNA-based methods. The cell population may be generated from a matched related donor that is a 9 / 10 match for HLA-A, -B, -C, -DQB1, and -DRB1, all of which are typed using high-throughput DNA-based methods. The cell population may be generated from a matched related donor that is an 8 / 10 match for HLA-A, -B, -C, -DQB1, and -DRB1, all of which are typed using high-throughput DNA-based methods. The cell population may be generated from a matched related donor that is a 7 / 10 match for HLA-A, -B, -C, -DQB1, and -DRB1, all of which are typed using high-throughput DNA-based methods. The cell population may be generated from a matched related donor that is 12 / 12 matched for HLA-A, -B, -C, -DQB1, -DRB1, and DPB1, all of which are typed using high-throughput DNA-based methods. The cell population may be generated from a matched related donor that is 11 / 12 matched for HLA-A, -B, -C, -DQB1, -DRB1, and DPB1, all of which are typed using high-throughput DNA-based methods. The cell population may be generated from a matched related donor that is 10 / 12 matched for HLA-A, -B, -C, -DQB1, -DRB1, and DPB1, all of which are typed using high-throughput DNA-based methods.Cell populations may be generated from matched related donors who are 9 / 12 matches for HLA-A, -B, -C, -DQB1, -DRB1, and DPB1, all of which are typed using high-throughput DNA-based methods.

[0127] The cell population may be generated from matched parent donors that are 8 / 8 matches for HLA-A, -B, -C, and -DRB1, all of which are typed using high-throughput DNA-based methods. The cell population may be generated from matched parent donors that are 7 / 8 matches for HLA-A, -B, -C, and -DRB1, all of which are typed using high-throughput DNA-based methods. The cell population may be generated from matched parent donors that are 6 / 8 matches for HLA-A, -B, -C, and -DRB1, all of which are typed using high-throughput DNA-based methods. The cell population may be generated from matched parent donors that are 10 / 10 matches for HLA-A, -B, -C, -DQB1, and -DRB1, all of which are typed using high-throughput DNA-based methods. The cell population may be generated from matched parent donors that are 9 / 10 matches for HLA-A, -B, -C, -DQB1, and -DRB1, all of which are typed using high-throughput DNA-based methods. The cell population may be generated from matched parent donors that are 8 / 10 matches for HLA-A, -B, -C, -DQB1, and -DRB1, all of which are typed using high-throughput DNA-based methods. The cell population may be generated from matched parent donors that are 7 / 10 matches for HLA-A, -B, -C, -DQB1, and -DRB1, all of which are typed using high-throughput DNA-based methods. The cell population may be generated from matched parent donors that are 12 / 12 matches for HLA-A, -B, -C, -DQB1, -DRB1, and -DRB1, all of which are typed using high-throughput DNA-based methods. The cell population may be generated from matched parent donors that are 11 / 12 matches for HLA-A, -B, -C, -DQB1, -DRB1, and DPB1, all of which are typed using high-throughput DNA-based methods. The cell population may be generated from matched parent donors that are 10 / 12 matches for HLA-A, -B, -C, -DQB1, -DRB1, and DPB1, all of which are typed using high-throughput DNA-based methods.Cell populations may be generated from matched parental donors that are 9 / 12 matches for HLA-A, -B, -C, -DQB1, -DRB1, and DPB1, all of which are typed using high-throughput DNA-based methods.

[0128] The cell population may be generated from a matched pediatric donor that is 8 / 8 matched for HLA-A, -B, -C, and -DRB1, all of which are typed using a high-throughput DNA-based method. The cell population may be generated from a matched pediatric donor that is 7 / 8 matched for HLA-A, -B, -C, and -DRB1, all of which are typed using a high-throughput DNA-based method. The cell population may be generated from a matched pediatric donor that is 6 / 8 matched for HLA-A, -B, -C, and -DRB1, all of which are typed using a high-throughput DNA-based method. The cell population may be generated from a matched pediatric donor that is 10 / 10 matched for HLA-A, -B, -C, -DQB1, and -DRB1, all of which are typed using a high-throughput DNA-based method. The cell population may be generated from a matched pediatric donor that is a 9 / 10 match for HLA-A, -B, -C, -DQB1, and -DRB1, all of which are typed using a high-throughput DNA-based method. The cell population may be generated from a matched pediatric donor that is an 8 / 10 match for HLA-A, -B, -C, -DQB1, and -DRB1, all of which are typed using a high-throughput DNA-based method. The cell population may be generated from a matched pediatric donor that is a 7 / 10 match for HLA-A, -B, -C, -DQB1, and -DRB1, all of which are typed using a high-throughput DNA-based method. The cell population may be generated from a matched pediatric donor that is a 12 / 12 match for HLA-A, -B, -C, -DQB1, -DRB1, and -DRB1, all of which are typed using a high-throughput DNA-based method. The cell population may be generated from a matched pediatric donor who is 11 / 12 matched for HLA-A, -B, -C, -DQB1, -DRB1, and DPB1, all of which are typed using high-throughput DNA-based methods. The cell population may be generated from a matched pediatric donor who is 10 / 12 matched for HLA-A, -B, -C, -DQB1, -DRB1, and DPB1, all of which are typed using high-throughput DNA-based methods.Cell populations may be generated from matched child donors who are 9 / 12 matches for HLA-A, -B, -C, -DQB1, -DRB1, and DPB1, all of which are typed using high-throughput DNA-based methods.

[0129] The cell population may be generated from matched sibling donors who are 8 / 8 matches for HLA-A, -B, -C, and -DRB1, all of which are typed using high-throughput DNA-based methods. The cell population may be generated from matched sibling donors who are 7 / 8 matches for HLA-A, -B, -C, and -DRB1, all of which are typed using high-throughput DNA-based methods. The cell population may be generated from matched sibling donors who are 6 / 8 matches for HLA-A, -B, -C, and -DRB1, all of which are typed using high-throughput DNA-based methods. The cell population may be generated from matched sibling donors who are 10 / 10 matches for HLA-A, -B, -C, -DQB1, and -DRB1, all of which are typed using high-throughput DNA-based methods. The cell population may be generated from matched sibling donors who are 9 / 10 matches for HLA-A, -B, -C, -DQB1, and -DRB1, all of which are typed using high-throughput DNA-based methods. The cell population may be generated from matched sibling donors who are 8 / 10 matches for HLA-A, -B, -C, -DQB1, and -DRB1, all of which are typed using high-throughput DNA-based methods. The cell population may be generated from matched sibling donors who are 7 / 10 matches for HLA-A, -B, -C, -DQB1, and -DRB1, all of which are typed using high-throughput DNA-based methods. The cell population may be generated from a matched pediatric donor who is 12 / 12 matched for HLA-A, -B, -C, -DQB1, -DRB1, and DPB1, all of which are typed using high-throughput DNA-based methods. The cell population may be generated from a matched pediatric donor who is 11 / 12 matched for HLA-A, -B, -C, -DQB1, -DRB1, and DPB1, all of which are typed using high-throughput DNA-based methods.The cell population may be generated from a matched pediatric donor who is a 10 / 12 match for HLA-A, -B, -C, -DQB1, -DRB1, and DPB1, all of which are typed using high-throughput DNA-based methods. The cell population may be generated from a matched pediatric donor who is a 9 / 12 match for HLA-A, -B, -C, -DQB1, -DRB1, and DPB1, all of which are typed using high-throughput DNA-based methods.

[0130] The cell population may be generated from matched grandparent donors who are 8 / 8 matches for HLA-A, -B, -C, and -DRB1, all of which are typed using high-throughput DNA-based methods. The cell population may be generated from matched grandparent donors who are 7 / 8 matches for HLA-A, -B, -C, and -DRB1, all of which are typed using high-throughput DNA-based methods. The cell population may be generated from matched grandparent donors who are 6 / 8 matches for HLA-A, -B, -C, and -DRB1, all of which are typed using high-throughput DNA-based methods. The cell population may be generated from matched grandparent donors who are 10 / 10 matches for HLA-A, -B, -C, -DQB1, and -DRB1, all of which are typed using high-throughput DNA-based methods. The cell population may be generated from matched grandparent donors who are 9 / 10 matches for HLA-A, -B, -C, -DQB1, and -DRB1, all of which are typed using high-throughput DNA-based methods. The cell population may be generated from matched grandparent donors who are 8 / 10 matches for HLA-A, -B, -C, -DQB1, and -DRB1, all of which are typed using high-throughput DNA-based methods. The cell population may be generated from matched grandparent donors who are 7 / 10 matches for HLA-A, -B, -C, -DQB1, and -DRB1, all of which are typed using high-throughput DNA-based methods. The cell population may be generated from matched grandparent donors who are 12 / 12 matches for HLA-A, -B, -C, -DQB1, -DRB1, and DPB1, all of which are typed using high-throughput DNA-based methods. The cell population may be generated from matched grandparent donors who are 11 / 12 matches for HLA-A, -B, -C, -DQB1, -DRB1, and DPB1, all of which are typed using high-throughput DNA-based methods. The cell population may be generated from matched grandparent donors who are 10 / 12 matches for HLA-A, -B, -C, -DQB1, -DRB1, and DPB1, all of which are typed using high-throughput DNA-based methods.Cell populations may be generated from matched grandparent donors who are 9 / 12 matches for HLA-A, -B, -C, -DQB1, -DRB1, and DPB1, all of which are typed using high-throughput DNA-based methods.

[0131] The cell population may be generated from a matched grandchild donor who is 8 / 8 matched for HLA-A, -B, -C, and -DRB1, all of which are typed using a high-throughput DNA-based method. The cell population may be generated from a matched grandchild donor who is 7 / 8 matched for HLA-A, -B, -C, and -DRB1, all of which are typed using a high-throughput DNA-based method. The cell population may be generated from a matched grandchild donor who is 6 / 8 matched for HLA-A, -B, -C, and -DRB1, all of which are typed using a high-throughput DNA-based method. The cell population may be generated from a matched grandchild donor who is 10 / 10 matched for HLA-A, -B, -C, -DQB1, and -DRB1, all of which are typed using a high-throughput DNA-based method. The cell population may be generated from a matched grandchild donor who is a 9 / 10 match for HLA-A, -B, -C, -DQB1, and -DRB1, all of which are typed using a high-throughput DNA-based method. The cell population may be generated from a matched grandchild donor who is an 8 / 10 match for HLA-A, -B, -C, -DQB1, and -DRB1, all of which are typed using a high-throughput DNA-based method. The cell population may be generated from a matched grandchild donor who is a 7 / 10 match for HLA-A, -B, -C, -DQB1, and -DRB1, all of which are typed using a high-throughput DNA-based method. The cell population may be generated from a matched grandchild donor who is a 12 / 12 match for HLA-A, -B, -C, -DQB1, -DRB1, and -DRB1, all of which are typed using a high-throughput DNA-based method. The cell population may be generated from a matched grandchild donor who is 11 / 12 matched for HLA-A, -B, -C, -DQB1, -DRB1, and DPB1, all of which are typed using high-throughput DNA-based methods. The cell population may be generated from a matched grandchild donor who is 10 / 12 matched for HLA-A, -B, -C, -DQB1, -DRB1, and DPB1, all of which are typed using high-throughput DNA-based methods.Cell populations may be generated from matched grandchild donors who are 9 / 12 matches for HLA-A, -B, -C, -DQB1, -DRB1, and DPB1, all of which are typed using high-throughput DNA-based methods.

[0132] The cell population may be generated from a matched aunt donor who is 8 / 8 matched for HLA-A, -B, -C, and -DRB1, all of which are typed using a high-throughput DNA-based method. The cell population may be generated from a matched aunt donor who is 7 / 8 matched for HLA-A, -B, -C, and -DRB1, all of which are typed using a high-throughput DNA-based method. The cell population may be generated from a matched aunt donor who is 6 / 8 matched for HLA-A, -B, -C, and -DRB1, all of which are typed using a high-throughput DNA-based method. The cell population may be generated from a matched aunt donor who is 10 / 10 matched for HLA-A, -B, -C, -DQB1, and -DRB1, all of which are typed using a high-throughput DNA-based method. The cell population may be generated from a matched aunt donor who is a 9 / 10 match for HLA-A, -B, -C, -DQB1, and -DRB1, all of which are typed using a high-throughput DNA-based method. The cell population may be generated from a matched aunt donor who is an 8 / 10 match for HLA-A, -B, -C, -DQB1, and -DRB1, all of which are typed using a high-throughput DNA-based method. The cell population may be generated from a matched aunt donor who is a 7 / 10 match for HLA-A, -B, -C, -DQB1, and -DRB1, all of which are typed using a high-throughput DNA-based method. The cell population may be generated from a matched aunt donor who is 12 / 12 matched for HLA-A, -B, -C, -DQB1, -DRB1, and DPB1, all of which are typed using high-throughput DNA-based methods. The cell population may be generated from a matched aunt donor who is 11 / 12 matched for HLA-A, -B, -C, -DQB1, -DRB1, and DPB1, all of which are typed using high-throughput DNA-based methods. The cell population may be generated from a matched aunt donor who is 10 / 12 matched for HLA-A, -B, -C, -DQB1, -DRB1, and DPB1, all of which are typed using high-throughput DNA-based methods.Cell populations may be generated from matched aunt donors who are 9 / 12 matches for HLA-A, -B, -C, -DQB1, -DRB1, and DPB1, all of which are typed using high-throughput DNA-based methods.

[0133] The cell population may be generated from a matched uncle donor that is 8 / 8 matched for HLA-A, -B, -C, and -DRB1, all of which are typed using a high-throughput DNA-based method. The cell population may be generated from a matched uncle donor that is 7 / 8 matched for HLA-A, -B, -C, and -DRB1, all of which are typed using a high-throughput DNA-based method. The cell population may be generated from a matched uncle donor that is 6 / 8 matched for HLA-A, -B, -C, and -DRB1, all of which are typed using a high-throughput DNA-based method. The cell population may be generated from a matched uncle donor that is 10 / 10 matched for HLA-A, -B, -C, -DQB1, and -DRB1, all of which are typed using a high-throughput DNA-based method. The cell population may be generated from a matched uncle donor that is a 9 / 10 match for HLA-A, -B, -C, -DQB1, and -DRB1, all of which are typed using a high-throughput DNA-based method. The cell population may be generated from a matched uncle donor that is an 8 / 10 match for HLA-A, -B, -C, -DQB1, and -DRB1, all of which are typed using a high-throughput DNA-based method. The cell population may be generated from a matched uncle donor that is a 7 / 10 match for HLA-A, -B, -C, -DQB1, and -DRB1, all of which are typed using a high-throughput DNA-based method. The cell population may be generated from a matched uncle donor who is 12 / 12 matched for HLA-A, -B, -C, -DQB1, -DRB1, and DPB1, all of which are typed using high-throughput DNA-based methods. The cell population may be generated from a matched uncle donor who is 11 / 12 matched for HLA-A, -B, -C, -DQB1, -DRB1, and DPB1, all of which are typed using high-throughput DNA-based methods. The cell population may be generated from a matched uncle donor who is 10 / 12 matched for HLA-A, -B, -C, -DQB1, -DRB1, and DPB1, all of which are typed using high-throughput DNA-based methods.Cell populations may be generated from matched uncle donors who are 9 / 12 matched for HLA-A, -B, -C, -DQB1, -DRB1, and DPB1, all of which are typed using high-throughput DNA-based methods.

[0134] The cell population may be generated from matched cousin donors who are 8 / 8 matches for HLA-A, -B, -C, and -DRB1, all of which are typed using high-throughput DNA-based methods. The cell population may be generated from matched cousin donors who are 7 / 8 matches for HLA-A, -B, -C, and -DRB1, all of which are typed using high-throughput DNA-based methods. The cell population may be generated from matched cousin donors who are 6 / 8 matches for HLA-A, -B, -C, and -DRB1, all of which are typed using high-throughput DNA-based methods. The cell population may be generated from matched cousin donors who are 10 / 10 matches for HLA-A, -B, -C, -DQB1, and -DRB1, all of which are typed using high-throughput DNA-based methods. The cell population may be generated from a matched cousin donor who is a 9 / 10 match for HLA-A, -B, -C, -DQB1, and -DRB1, all of which are typed using a high-throughput DNA-based method. The cell population may be generated from a matched cousin donor who is an 8 / 10 match for HLA-A, -B, -C, -DQB1, and -DRB1, all of which are typed using a high-throughput DNA-based method. The cell population may be generated from a matched cousin donor who is a 7 / 10 match for HLA-A, -B, -C, -DQB1, and -DRB1, all of which are typed using a high-throughput DNA-based method. The cell population may be generated from matched cousin donors who are 12 / 12 matches for HLA-A, -B, -C, -DQB1, -DRB1, and DPB1, all of which are typed using high-throughput DNA-based methods. The cell population may be generated from matched cousin donors who are 11 / 12 matches for HLA-A, -B, -C, -DQB1, -DRB1, and DPB1, all of which are typed using high-throughput DNA-based methods. The cell population may be generated from matched cousin donors who are 10 / 12 matches for HLA-A, -B, -C, -DQB1, -DRB1, and DPB1, all of which are typed using high-throughput DNA-based methods.Cell populations may be generated from matched cousin donors who are 9 / 12 matches for HLA-A, -B, -C, -DQB1, -DRB1, and DPB1, all of which are typed using high-throughput DNA-based methods.

[0135] 2. Specific Embodiments In some embodiments, HLA incompatibility occurs because the allogeneic related or unrelated donor is homozygous for the HLA allele, but the recipient subject is heterozygous for the HLA allele. In some embodiments, HLA incompatibility occurs because the allogeneic related or unrelated donor is heterozygous for the HLA allele, but the recipient subject is homozygous for the HLA allele. In some embodiments, HLA incompatibility occurs because both the allogeneic related or unrelated donor and the recipient subject are heterozygous for the HLA allele.

[0136] In various embodiments, the cell population of the present disclosure is allogeneic compared to a human subject.In some embodiments, the cell population of the present disclosure is obtained from a donor that is HLA-matched compared to a human subject.In several embodiments, the cell population of the present disclosure is obtained from a donor that is HLA-mismatched compared to a human subject.In various embodiments, the cell population of the present disclosure is obtained from a donor that is half-matched compared to a human subject.

[0137] One or more cell populations of the present disclosure can be obtained from a single donor, for example, from mobilized peripheral blood apheresis of a single donor. HSPCs, Tregs, iNKTs, Tmems, or any combination thereof can be obtained from a single donor.

[0138] One or more cell populations of the present disclosure can be obtained from a single donor, and one or more additional cell populations of the present disclosure can be obtained from a second donor. One cell population of the present disclosure can be obtained from a single donor, and a second cell population of the present disclosure can be obtained from multiple donors. Cell populations of the present disclosure can be obtained from multiple donors, for example, from mobilized peripheral blood apheresis of multiple donors. HSPCs can be obtained from multiple donors. Tregs can be obtained from multiple donors. Tmems can be obtained from multiple donors. iNKTs can be obtained from multiple donors.

[0139] In embodiments, each cell population is provided as a separate cell population and is derived from a single human blood donor.

[0140] The cell population may, for example, include cells from one or more donors, each of which has been HLA typed to determine the degree of HLA match with the subject receiving the cell population.

[0141] In some embodiments, the population of cells enriched for Tregs and / or Tmems is allogeneic compared to a human subject. ... + CD25 - CD45RA + The population of T cell (Tcon) depleted cells is homogeneous compared to human subjects.

[0142] In some embodiments, the population of cells enriched for Tmem and / or Treg is obtained from a donor that is HLA-matched relative to the human subject. ... + CD25 - CD45RA + A population of T cell (Tcon) depleted cells is obtained from a donor that is HLA-matched relative to the human subject.

[0143] In some embodiments, the population of cells enriched for Tmem and / or Treg is obtained from a donor that is HLA-mismatched relative to the human subject. ... + CD25 - CD45RA + A population of T cell (Tcon) depleted cells is obtained from a donor that is HLA-mismatched compared to the human subject.

[0144] In some embodiments, the population of cells enriched for Tmem and / or Treg is obtained from a donor that is half-matched relative to the human subject. ... + CD25 - CD45RA + A population of T cell (Tcon) depleted cells is obtained from a donor that is half-matched relative to the human subject.

[0145] The cell population may be derived from an allogeneic donor. The cell population may be generated from a donor who is a first-degree relative of the subject. The cell population may be generated from a donor who is a second-degree relative of the subject. The cell population may be generated from a donor who is unrelated to the subject. The cell population may be generated from a donor who is HLA-matched to the recipient subject. The cell population may be generated from a donor who is HLA-mismatched to the recipient subject. The cell population may be generated from a donor who is half-matched to the recipient subject. The cell population may be generated from a donor who is related to the recipient subject, for example, a parent, child, sibling, grandparent, grandchild, uncle, aunt, or cousin. The cell population may be generated from a donor who is at least 16 years of age. The cell population may be generated from a donor who is at least 18 years of age.

[0146] The cell population may be generated from a donor who meets the eligibility criteria for a donor of viable leukocyte-rich cells or tissue as defined in 21 CFR § 1271 2018 and the associated FDA Guidance for Industry. For example, the cell population may be generated from a donor who meets the eligibility criteria outlined in any one or more of the following: Eligibility Determination for Donors of Human Cells,Tissues,and Cellular and Tissue-Based Products,2007;Use of Donor Screening Tests to Test Donors of Human Cells,Tissues and Cellular and Tissue-Based Products for Infection with Treponema pallidum(Syphilis),2015;Use of Nucleic Acid Tests to Reduce the Risk of Transmission of Hepatitis B Virus from Donors of Human Cells,Tissues,and Cellular and Tissue-Based Products,2016;Use of Nucleic Acid Tests to Reduce the Risk of Transmission of West Nile Virus from Living Donors of Human Cells,Tissues,and Cellular and Tissue-Based Products(HCT / Ps),2016;and Donor Screening Recommendations to Reduce the Risk of Transmission of Zika Virus by Human Cells, Tissues, and Cellular and Tissue-Based Products, 2018). The cell population may be generated from donors who meet any criteria for donation as specified by standard NMDP guidelines (NMDP donors).

[0147] The cell population may be generated from a donor who shows no evidence of active infection. The cell population may be generated from a donor who is not seropositive for HIV-1 or -2, HTLV-1 or 2. The cell population may be generated from a donor who is not positive for anti-hepatitis C (HCV) antibodies or HCV NATs. The cell population may be generated from a donor who tests negative for chronic HBV infection. The cell population may be generated from a donor who is not at high risk for Zika virus infection, defined as any of the following: (i) a medical diagnosis of Zika virus infection within the past six months; (ii) residence in or travel to an area with active Zika virus transmission within the past six months; or (iii) unprotected intercourse with a person known to have either risk factor (i) or (ii) within the past six months. The cell population may be generated from a donor who has no signs or symptoms consistent with active Zika virus infection.

[0148] One or more cell populations of the present disclosure can be obtained from a single donor, for example, from mobilized peripheral blood apheresis of a single donor. The cell populations can include HSPCs, Tregs, naive conventional αβ-T cells, or naive conventional CD3 + CD25 - CD45RA + T cells (Tcon), iNKT, Tmem, or any combination thereof can be obtained from a single donor. The population of cells provided herein can be obtained from multiple donors, for example, from mobilized peripheral blood apheresis of multiple donors. HSPCs can be obtained from multiple donors. Tregs can be obtained from multiple donors. Naive conventional αβ-T cells or naive conventional CD3 + CD25 - CD45RA + T cells (Tcon) can be obtained from multiple donors. iNKT can be obtained from multiple donors. Tmem can be obtained from multiple donors. Naive conventional αβ-T cells or naive conventional CD3+ CD25 - CD45RA + T cells (Tcon) can be depleted from one or more cell populations of the present disclosure.

[0149] Cell dose The dose of a cell population administered to a subject (e.g., a human subject) may be based on the subject's body weight. In some embodiments, the subject's body weight may be used to determine the dose of one or more cell populations administered to the subject. In some embodiments, the cell dose may be based on a calculated body weight (e.g., ideal body weight or IBW) for the subject's dose calculation instead of the subject's actual body weight (e.g., actual body weight). In some embodiments, IBW is a preferred dose calculation method to avoid erroneous cell doses due to excess body fat and / or muscle mass. In some embodiments, a subject's ideal body weight can be calculated using the subject's height and sex. In some embodiments, a subject's ideal body weight can be calculated using Devine's method (DeVine 1974). In some embodiments, other methods of calculating a subject's IBW can be used. For example, there are other methods of determining a subject's body fat percentage. In some embodiments, one or more cell populations of the present disclosure (e.g., isolated CD45 + The dose of the cell population may be based on the subject's adjusted ideal body weight (AIBW) if the subject's actual body weight is greater than 120% of IBW.

[0150] In some embodiments, a human subject of the present disclosure has a body weight in the range of about 4 kilograms (kg) to about 200 kilograms (kg). In some embodiments, a human subject has a body weight in the range of about 4 kilograms, about 5 kilograms, about 6 kilograms, about 7 kilograms, about 8 kilograms, about 9 kilograms, about 10 kilograms, about 11 kilograms, about 12 kilograms, about 13 kilograms, about 14 kilograms, about 15 kilograms, about 16 kilograms, about 17 kilograms, about 18 kilograms, about 19 kilograms, about 20 kilograms, about 21 kilograms, about 22 kilograms, about 23 kilograms, about 24 kilograms, about 25 kilograms, about 26 kilograms, about 27 kilograms, about 28 kilograms, about 29 kg, approximately 30 kg, approximately 31 kg, approximately 32 kg, approximately 33 kg, approximately 34 kg, approximately 35 kg, approximately 36 kg, approximately 37 kg, approximately 38 kg, approximately 39 kg, approximately 40 kg, approximately 41 kg, approximately 42 kg, approximately 43 kg, approximately 44 kg, approximately 45 kg, approximately 46 kg, approximately 47 kg, approximately 48 kg, approximately 49 kg, approximately 50 kg, approximately 51 kg, approximately 52 kg, approximately 53 kg, approximately 54 kg, approximately 55 Kilograms, approximately 56 kg, approximately 57 kg, approximately 58 kg, approximately 59 kg, approximately 60 kg, approximately 61 kg, approximately 62 kg, approximately 63 kg, approximately 64 kg, approximately 65 kg, approximately 66 kg, approximately 67 kg, approximately 68 kg, approximately 69 kg, approximately 70 kg, approximately 71 kg, approximately 72 kg, approximately 73 kg, approximately 74 kg, approximately 75 kg, approximately 76 kg, approximately 77 kg, approximately 78 kg, approximately 79 kg, approximately 80 kg, approximately 81 kg grams, approximately 82 kilograms, approximately 83 kilograms, approximately 84 kilograms, approximately 85 kilograms, approximately 86 kilograms, approximately 87 kilograms, approximately 88 kilograms, approximately 89 kilograms, approximately 90 kilograms, approximately 91 kilograms, approximately 92 kilograms, approximately 93 kilograms, approximately 94 kilograms, approximately 95 kilograms, approximately 96 kilograms, approximately 97 kilograms, approximately 98 kilograms, approximately 99 kilograms, approximately 100 kilograms, approximately 105 kilograms, approximately 110 kilograms, approximately 115 kilograms, approximately 120 kilograms, approximately 125 kilograms, approximately 130 kilograms,and weighing about 135 kilograms, about 140 kilograms, about 145 kilograms, about 150 kilograms, about 155 kilograms, about 160 kilograms, about 165 kilograms, about 170 kilograms, about 175 kilograms, about 180 kilograms, about 185 kilograms, about 190 kilograms, about 195 kilograms, or about 200 kilograms.

[0151] HSPC In some embodiments, the population of cells of the present disclosure comprising HSPCs, or comprising at least one dose of HSPCs, is about 1 x 10 per kilogram of actual or ideal body weight of a human subject receiving a treatment or cell therapy product of the present disclosure. 4 ~Approx. 1×10 9 In some embodiments, the population of cells comprising HSPCs, or comprising at least one dose of HSPCs, comprises about 1 x 10 HSPCs per kilogram of IBW in a human subject. 4 ~Approx. 1×10 9 Contains HSPCs.

[0152] The population of HSPCs, or the dose of HSPCs, is at least about 1 x 10 per kilogram (kg) of actual or (adjusted) ideal body weight of a human subject. 4 At least about 2 x 10 pieces 4 pieces, at least about 3 x 10 4 pieces, at least about 4 x 10 4 pieces, at least about 5 x 10 4 pieces, at least about 6 x 10 4 pieces, at least about 7 x 10 4 pieces, at least about 8 x 10 4 pieces, at least about 9 x 10 4 At least about 1 x 10 pieces 5 At least about 2 x 10 pieces 5 pieces, at least about 3 x 10 5 pieces, at least about 4 x 10 5 pieces, at least about 5 x 10 5 pieces, at least about 6 x 10 5 pieces, at least about 7 x 10 5 pieces, at least about 8 x 10 5 pieces, at least about 9 x 10 5At least about 1 x 10 pieces 6 pieces, at least about 1.1 x 10 6 At least about 1.2 x 10 6 pieces, at least about 1.3 x 10 6 pieces, at least about 1.4 x 10 6 At least about 1.5 x 10 6 pieces, at least about 1.6 x 10 6 pieces, at least about 1.7 x 10 6 pieces, at least about 1.8 x 10 6 pieces, at least about 1.9 x 10 6 At least about 2 x 10 pieces 6 At least approximately 2.1 x 10 6 At least about 2.2 x 10 6 At least about 2.3 x 10 6 At least about 2.4 x 10 6 At least about 2.5 x 10 6 pieces, at least about 2.6 x 10 6 pieces, at least about 2.7 x 10 6 At least about 2.8 x 10 6 pieces, at least about 2.9 x 10 6 pieces, at least about 3 x 10 6 At least approximately 3.1 x 10 6 At least about 3.2 x 10 6 pieces, at least about 3.3 x 10 6 pieces, at least about 3.4 x 10 6 At least about 3.5 x 10 6 pieces, at least about 3.6 x 10 6 pieces, at least about 3.7 x 10 6 pieces, at least about 3.8 x 10 6 pieces, at least about 3.9 x 10 6 pieces, at least about 4 x 10 6 At least about 4.1 x 10 6 pieces, at least about 4.2 x 10 6 pieces, at least about 4.3 x 10 6 pieces, at least about 4.4 x 10 6 At least about 4.5 x 10 6 pieces, at least about 4.6 x 10 6pieces, at least about 4.7 x 10 6 pieces, at least about 4.8 x 10 6 pieces, at least about 4.9 x 10 6 pieces, at least about 5 x 10 6 pieces, at least about 5.1 x 10 6 At least about 5.2 x 10 6 pieces, at least about 5.3 x 10 6 pieces, at least about 5.4 x 10 6 At least about 5.5 x 10 6 pieces, at least about 5.6 x 10 6 pieces, at least about 5.7 x 10 6 pieces, at least about 5.8 x 10 6 pieces, at least about 5.9 x 10 6 pieces, at least about 6 x 10 6 pieces, at least about 6.1 x 10 6 pieces, at least about 6.2 x 10 6 pieces, at least about 6.3 x 10 6 pieces, at least about 6.4 x 10 6 At least approximately 6.5 x 10 6 pieces, at least about 6.6 x 10 6 pieces, at least about 6.7 x 10 6 pieces, at least about 6.8 x 10 6 pieces, at least about 6.9 x 10 6 pieces, at least about 7 x 10 6 pieces, at least about 7.1 x 10 6 pieces, at least about 7.2 x 10 6 pieces, at least about 7.3 x 10 6 pieces, at least about 7.4 x 10 6 At least about 7.5 x 10 6 pieces, at least about 7.6 x 10 6 pieces, at least about 7.7 x 10 6 pieces, at least about 7.8 x 10 6 pieces, at least about 7.9 x 10 6 pieces, at least about 8 x 10 6 pieces, at least about 8.1 x 10 6 pieces, at least about 8.2 x 10 6 pieces, at least about 8.3 x 10 6pieces, at least about 8.4 x 10 6 At least about 8.5 x 10 6 pieces, at least about 8.6 x 10 6 pieces, at least about 8.7 x 10 6 pieces, at least about 8.8 x 10 6 pieces, at least about 8.9 x 10 6 pieces, at least about 9 x 10 6 pieces, at least about 9.1 x 10 6 pieces, at least about 9.2 x 10 6 pieces, at least about 9.3 x 10 6 pieces, at least about 9.4 x 10 6 pieces, at least about 9.5 x 10 6 pieces, at least about 9.6 x 10 6 pieces, at least about 9.7 x 10 6 pieces, at least about 9.8 x 10 6 pieces, at least about 9.9 x 10 6 At least about 1 x 10 pieces 7 At least about 1.5 x 10 7 At least about 2 x 10 pieces 7 At least about 2.5 x 10 7 pieces, at least about 3 x 10 7 At least about 3.5 x 10 7 pieces, at least about 4 x 10 7 At least about 4.5 x 10 7 pieces, at least about 5 x 10 7 At least about 5.5 x 10 7 pieces, at least about 6 x 10 7 At least approximately 6.5 x 10 7 pieces, at least about 7 x 10 7 At least about 7.5 x 10 7 pieces, at least about 8 x 10 7 At least about 8.5 x 10 7 pieces, at least about 9 x 10 7 pieces, at least about 9.5 x 10 7 At least about 1 x 10 pieces 8 At least about 1.5 x 10 8 At least about 2 x 10 pieces 8 At least about 2.5 x 10 8pieces, at least about 3 x 10 8 At least about 3.5 x 10 8 pieces, at least about 4 x 10 7 At least about 4.5 x 10 8 pieces, at least about 5 x 10 8 At least about 5.5 x 10 8 pieces, at least about 6 x 10 8 At least approximately 6.5 x 10 8 pieces, at least about 7 x 10 8 At least about 7.5 x 10 8 pieces, at least about 8 x 10 8 At least about 8.5 x 10 8 pieces, at least about 9 x 10 8 pieces, at least about 9.5 x 10 8 At least about 1 x 10 pieces 9 The cells may contain 1 or more HSPCs.

[0153] The population of HSPCs, or the dose of HSPCs, may be up to about 1 × 10 per kilogram (kg) of actual or (adjusted) ideal body weight in a human subject. 4 pieces, up to about 2 x 10 4 pieces, up to about 3 x 10 4 pieces, up to about 4 x 10 4 pieces, up to about 5 x 10 4 pieces, up to about 6 x 10 4 pieces, up to about 7 x 10 4 pieces, up to about 8 x 10 4 pieces, up to about 9 x 10 4 pieces, up to about 1 x 10 5 pieces, up to about 2 x 10 5 pieces, up to about 3 x 10 5 pieces, up to about 4 x 10 5 pieces, up to about 5 x 10 5 pieces, up to about 6 x 10 5 pieces, up to about 7 x 10 5 pieces, up to about 8 x 10 5 pieces, up to about 9 x 10 5 pieces, up to about 1 x 10 6 pieces, up to about 1.1 x 10 6 pieces, up to about 1.2 × 10 6 pieces, up to about 1.3 x 106 pieces, up to about 1.4 x 10 6 pieces, up to about 1.5 x 10 6 pieces, up to about 1.6 x 10 6 pieces, up to about 1.7 x 10 6 pieces, up to about 1.8 x 10 6 pieces, up to about 1.9 x 10 6 pieces, up to about 2 x 10 6 pieces, up to approximately 2.1 x 10 6 pieces, up to approximately 2.2 x 10 6 pieces, up to about 2.3 x 10 6 pieces, up to approximately 2.4 x 10 6 pieces, up to about 2.5 x 10 6 pieces, up to about 2.6 x 10 6 pieces, up to about 2.7 x 10 6 pieces, up to approximately 2.8 x 10 6 pieces, up to approximately 2.9 x 10 6 pieces, up to about 3 x 10 6 pieces, up to approximately 3.1 x 10 6 pieces, up to approximately 3.2 x 10 6 pieces, up to about 3.3 x 10 6 pieces, up to approximately 3.4 x 10 6 pieces, up to about 3.5 x 10 6 pieces, up to about 3.6 x 10 6 pieces, up to approximately 3.7 x 10 6 pieces, up to approximately 3.8 x 10 6 pieces, up to approximately 3.9 x 10 6 pieces, up to about 4 x 10 6 pieces, up to approximately 4.1 x 10 6 pieces, up to approximately 4.2 x 10 6 pieces, up to about 4.3 x 10 6 pieces, up to about 4.4 x 10 6 pieces, up to about 4.5 x 10 6 pieces, up to about 4.6 x 10 6 pieces, up to about 4.7 x 10 6 pieces, up to about 4.8 x 10 6 pieces, up to approximately 4.9 x 10 6 pieces, up to about 5 x 10 6 pieces, up to approximately 5.1 x 10 6 pieces, up to approximately 5.2 x 10 6 pieces, up to about 5.3 x 10 6pieces, up to approximately 5.4 x 10 6 pieces, up to about 5.5 x 10 6 pieces, up to about 5.6 x 10 6 pieces, up to about 5.7 x 10 6 pieces, up to approximately 5.8 x 10 6 pieces, up to approximately 5.9 x 10 6 pieces, up to about 6 x 10 6 pieces, up to approximately 6.1 x 10 6 pieces, up to approximately 6.2 x 10 6 pieces, up to approximately 6.3 x 10 6 pieces, up to approximately 6.4 x 10 6 pieces, up to about 6.5 x 10 6 pieces, up to approximately 6.6 x 10 6 pieces, up to approximately 6.7 x 10 6 pieces, up to approximately 6.8 x 10 6 pieces, up to approximately 6.9 x 10 6 pieces, up to about 7 x 10 6 pieces, up to approximately 7.1 x 10 6 pieces, up to approximately 7.2 x 10 6 pieces, up to approximately 7.3 x 10 6 pieces, up to approximately 7.4 x 10 6 pieces, up to about 7.5 x 10 6 pieces, up to approximately 7.6 x 10 6 pieces, up to approximately 7.7 x 10 6 pieces, up to approximately 7.8 x 10 6 pieces, up to approximately 7.9 x 10 6 pieces, up to about 8 x 10 6 pieces, up to approximately 8.1 x 10 6 pieces, up to approximately 8.2 x 10 6 pieces, up to approximately 8.3 x 10 6 pieces, up to approximately 8.4 x 10 6 pieces, up to approximately 8.5 x 10 6 pieces, up to approximately 8.6 x 10 6 pieces, up to approximately 8.7 x 10 6 pieces, up to approximately 8.8 x 10 6 pieces, up to approximately 8.9 x 10 6 pieces, up to about 9 x 10 6 pieces, up to approximately 9.1 x 10 6 pieces, up to approximately 9.2 x 10 6 pieces, up to approximately 9.3 x 10 6pieces, up to approximately 9.4 x 10 6 pieces, up to about 9.5 x 10 6 pieces, up to about 9.6 x 10 6 pieces, up to approximately 9.7 x 10 6 pieces, up to approximately 9.8 x 10 6 pieces, up to approximately 9.9 x 10 6 pieces, up to about 1 x 10 7 pieces, up to about 1.5 x 10 7 pieces, up to about 2 x 10 7 pieces, up to about 2.5 x 10 7 pieces, up to about 3 x 10 7 pieces, up to about 3.5 x 10 7 pieces, up to about 4 x 10 7 pieces, up to about 4.5 x 10 7 pieces, up to about 5 x 10 7 pieces, up to about 5.5 x 10 7 pieces, up to about 6 x 10 7 pieces, up to about 6.5 x 10 7 pieces, up to about 7 x 10 7 pieces, up to about 7.5 x 10 7 pieces, up to about 8 x 10 7 pieces, up to approximately 8.5 x 10 7 pieces, up to about 9 x 10 7 pieces, up to about 9.5 x 10 7 pieces, up to about 1 x 10 8 pieces, up to about 1.5 x 10 8 pieces, up to about 2 x 10 8 pieces, up to about 2.5 x 10 8 pieces, up to about 3 x 10 8 pieces, up to about 3.5 x 10 8 ...

Claims

1. Isolated CD45 ＋ A cell therapy product comprising a population of cells, the isolated CD45 ＋ A population of cells comprising: a) about 1.0 x 10 per kilogram of body weight of a human subject receiving said product ５ ~Approx. 1.0×10 ８ CD34 ＋ A dose of hematopoietic stem and progenitor cells (HSPCs), or approximately 5.0 x 10 ５ ~Approx. 1.5×10 １０ CD34 ＋ total dose of hematopoietic stem and progenitor cells (HSPCs), b) about 1.0 x 10 per kilogram of body weight of the human subject receiving the product ５ ~Approx. 1.0×10 ８ CD45RA － A dose of memory T cells (Tmem), or about 5.0 x 10 ５ ~Approx. 1.5×10 １０ CD45RA － the total dose of memory T cells (Tmem), and c) about 1.0 x 10 per kilogram of body weight of the human subject receiving the product ５ ~Approx. 2.0×10 ７ Fresh CD4 ＋ CD25 ＋ CD127 ｄｉｍ A dose of regulatory T cells (Tregs), or approximately 5.0 x 10 ５ ~Approx. 3.0×10 ９ Pieces of isolated fresh ＋ CD4 ＋ CD25 ＋ CD127 ｄｉｍ Total dose of regulatory T cells (Treg) Including, The cell therapy product is administered at a dose of about 5.0 x 10 per kilogram of body weight of the human subject receiving the product. ５ < naive conventional CD3 ＋ CD25 － CD45RA ＋ T cells (Tcon), approximately 6.0 x 10 ７ Less than 100 total naive conventional CD3 ＋ CD25 － CD45RA ＋ T cells (T), or approximately 1.0 x 10 ６ Less than 100 total naive conventional CD3 ＋ CD25 － CD45RA ＋ Naive conventional CD3 containing T cells (Tcon) ＋ CD25 － CD45RA ＋ T cells (Tcon) are depleted, and The isolated CD45 ＋ The population of cells is formulated with an excipient at neutral pH; Cell therapy products.

2. a) the dose of HSPCs is about 1.0 x 10 per kilogram of body weight of the human subject receiving the product ５ or more HSPCs, about 2.0 x 10 per kilogram of body weight of the human subject receiving the product ５ or more HSPCs, about 3.0 x 10 per kilogram of body weight of the human subject receiving the product ５ or more HSPCs, about 4.0 x 10 per kilogram of body weight of the human subject receiving the product ５ or more HSPCs, about 5.0 x 10 per kilogram of body weight of the human subject receiving the product ５ or more than about 6.0 x 10 HSPCs per kilogram of body weight of the human subject receiving the product ５ or more HSPCs per kilogram of body weight of the human subject receiving the product, ５ or more HSPCs, about 8.0 x 10 per kilogram of body weight of the human subject receiving the product ５ or more HSPCs, about 9.0 x 10 per kilogram of body weight of the human subject receiving the product ５ or more HSPCs, about 1.0 x 10 per kilogram of body weight of the human subject receiving the product ６ or more HSPCs, about 1.5 x 10 per kilogram of body weight of the human subject receiving the product ６ or more HSPCs, about 2.0 x 10 per kilogram of body weight of the human subject receiving the product ６ or more HSPCs, about 2.5 x 10 per kilogram of body weight of the human subject receiving the product ６ or more HSPCs, about 3.0 x 10 per kilogram of body weight of the human subject receiving the product ６ or more HSPCs, about 3.5 x 10 per kilogram of body weight of the human subject receiving the product ６ or more HSPCs, about 4.0 x 10 per kilogram of body weight of the human subject receiving the product ６ or more HSPCs, about 4.5 x 10 per kilogram of body weight of the human subject receiving the product ６ or more HSPCs, about 5.0 x 10 per kilogram of body weight of the human subject receiving the product ６ or more HSPCs, about 5.5 x 10 per kilogram of body weight of the human subject receiving the product ６ or more than about 6.0 x 10 HSPCs per kilogram of body weight of the human subject receiving the product ６ or more than about 6.5 x 10 HSPCs per kilogram of body weight of the human subject receiving the product ６ or more HSPCs per kilogram of body weight of the human subject receiving the product, ６ or more HSPCs, about 7.5 x 10 per kilogram of body weight of the human subject receiving the product ６ or more HSPCs, about 8.0 x 10 per kilogram of body weight of the human subject receiving the product ６ or more HSPCs, about 8.5 x 10 per kilogram of body weight of the human subject receiving the product ６ or more HSPCs, about 9.0 x 10 per kilogram of body weight of the human subject receiving the product ６ or more HSPCs, about 9.5 x 10 per kilogram of body weight of the human subject receiving the product ６ or more HSPCs, about 1.0 x 10 per kilogram of body weight of the human subject receiving the product ７ or more HSPCs, about 1.5 x 10 per kilogram of body weight of the human subject receiving the product ７ or more HSPCs, about 2.0 x 10 per kilogram of body weight of the human subject receiving the product ７ or more HSPCs, about 2.5 x 10 per kilogram of body weight of the human subject receiving the product ７ or more HSPCs, about 3.0 x 10 per kilogram of body weight of the human subject receiving the product ７ or more HSPCs, about 3.5 x 10 per kilogram of body weight of the human subject receiving the product ７ or more HSPCs, about 4.0 x 10 per kilogram of body weight of the human subject receiving the product ７ or more HSPCs, about 4.5 x 10 per kilogram of body weight of the human subject receiving the product ７ or more HSPCs, about 5.0 x 10 per kilogram of body weight of the human subject receiving the product ７ or more HSPCs, about 5.5 x 10 per kilogram of body weight of the human subject receiving the product ７ or more than about 6.0 x 10 HSPCs per kilogram of body weight of the human subject receiving the product ７ or more than about 6.5 x 10 HSPCs per kilogram of body weight of the human subject receiving the product ７ or more HSPCs per kilogram of body weight of the human subject receiving the product, ７ or more HSPCs, about 7.5 x 10 per kilogram of body weight of the human subject receiving the product ７ or more HSPCs, about 8.0 x 10 per kilogram of body weight of the human subject receiving the product ７ or more HSPCs, about 8.5 x 10 per kilogram of body weight of the human subject receiving the product ７ or more HSPCs, about 9.0 x 10 per kilogram of body weight of the human subject receiving the product ７ or more HSPCs, about 9.5 x 10 per kilogram of body weight of the human subject receiving the product ７ or more than about 1.0 x 10 HSPCs per kilogram of body weight of the human subject receiving the product. ８ and / or b) the dose of HSPCs is about 5.0 x 10 ５ HSPCs, approximately 6.0 x 10 ５ HSPCs, approximately 7.0 x 10 ５ HSPCs, approximately 8.0 x 10 ５ HSPCs, approximately 9.0 x 10 ５ HSPCs or more, about 1.0 x 10 ６ HSPCs, approximately 1.5 x 10 ６ HSPCs, approximately 2.0 x 10 ６ HSPCs, approximately 2.5 x 10 ６ HSPCs, approximately 3.0 x 10 ６ HSPCs, approximately 3.5 x 10 ６ HSPCs, approximately 4.0 x 10 ６ HSPCs, approximately 4.5 x 10 ６ HSPCs, approximately 5.0 x 10 ６ 5.5 x 10 or more HSPCs ６ HSPCs, approximately 6.0 x 10 ６ HSPCs, approximately 6.5 x 10 ６ HSPCs, approximately 7.0 x 10 ６ HSPCs, approximately 7.5 x 10 ６ HSPCs, approximately 8.0 x 10 ６ HSPCs, approximately 8.5 x 10 ６ HSPCs, approximately 9.0 x 10 ６ HSPCs, approximately 9.5 x 10 ６ HSPCs or more, about 1.0 x 10 ７ HSPCs or more, approximately 1.5 x 10 ７ HSPCs, approximately 2.0 x 10 ７ HSPCs, approximately 2.5 x 10 ７ HSPCs, approximately 3.0 x 10 ７ HSPCs, approximately 3.5 x 10 ７ HSPCs, approximately 4.0 x 10 ７ HSPCs, approximately 4.5 x 10 ７ HSPCs, approximately 5.0 x 10 ７ 5.5 x 10 or more HSPCs ７ HSPCs, approximately 6.0 x 10 ７ HSPCs, approximately 6.5 x 10 ７ HSPCs, approximately 7.0 x 10 ７ HSPCs, approximately 7.5 x 10 ７ HSPCs, approximately 8.0 x 10 ７ HSPCs, approximately 8.5 x 10 ７ HSPCs, approximately 9.0 x 10 ７ HSPCs, approximately 9.5 x 10 ７ HSPCs or more, about 1.0 x 10 ８ HSPCs or more, approximately 1.5 x 10 ８ HSPCs, approximately 2.0 x 10 ８ HSPCs, approximately 2.5 x 10 ８ HSPCs, approximately 3.0 x 10 ８ HSPCs, approximately 3.5 x 10 ８ HSPCs, approximately 4.0 x 10 ８ HSPCs, approximately 4.5 x 10 ８ HSPCs, approximately 5.0 x 10 ８ 5.5 x 10 or more HSPCs ８ HSPCs, approximately 6.0 x 10 ８ HSPCs, approximately 6.5 x 10 ８ HSPCs, approximately 7.0 x 10 ８ HSPCs, approximately 7.5 x 10 ８ HSPCs, approximately 8.0 x 10 ８ HSPCs, approximately 8.5 x 10 ８ HSPCs, approximately 9.0 x 10 ８ HSPCs, approximately 9.5 x 10 ８ HSPCs or more, about 1.0 x 10 ９ HSPCs or more, approximately 1.5 x 10 ９ HSPCs, approximately 2.0 x 10 ９ HSPCs, approximately 2.5 x 10 ９ HSPCs, approximately 3.0 x 10 ９ HSPCs, approximately 3.5 x 10 ９ HSPCs, approximately 4.0 x 10 ９ HSPCs, approximately 4.5 x 10 ９ HSPCs, approximately 5.0 x 10 ９ 5.5 x 10 or more HSPCs ９ HSPCs, approximately 6.0 x 10 ９ HSPCs, approximately 6.5 x 10 ９ HSPCs, approximately 7.0 x 10 ９ HSPCs, approximately 7.5 x 10 ９ HSPCs, approximately 8.0 x 10 ９ HSPCs, approximately 8.5 x 10 ９ HSPCs, approximately 9.0 x 10 ９ HSPCs, approximately 9.5 x 10 ９ HSPCs or more, about 1.0 x 10 １０ HSPCs or more, or about 1.5 x 10 １０ and / or c) the dose of Tmem is about 1.0 x 10 per kilogram of body weight of the human subject receiving the product ５ or more Tmem, about 2.0 x 10 per kilogram of body weight of the human subject receiving the product ５ or more Tmem, about 3.0 x 10 per kilogram of body weight of the human subject receiving the product ５ or more Tmem, about 4.0 x 10 per kilogram of body weight of the human subject receiving the product ５ or more Tmem, about 5.0 x 10 per kilogram of body weight of the human subject receiving the product ５ or more Tmem, about 6.0 x 10 per kilogram of body weight of the human subject receiving the product ５ or more Tmem, about 7.0 x 10 per kilogram of body weight of the human subject receiving the product ５ or more Tmem, about 8.0 x 10 per kilogram of body weight of the human subject receiving the product ５ or more Tmem, about 9.0 x 10 per kilogram of body weight of the human subject receiving the product ５ or more Tmem, about 1.0 x 10 per kilogram of body weight of the human subject receiving the product ６ or more Tmem, about 1.5 x 10 per kilogram of body weight of the human subject receiving the product ６ or more Tmem, about 2.0 x 10 per kilogram of body weight of the human subject receiving the product ６ or more Tmem, about 2.5 x 10 per kilogram of body weight of the human subject receiving the product ６ or more Tmem, about 3.0 x 10 per kilogram of body weight of the human subject receiving the product ６ or more Tmem, about 3.5 x 10 per kilogram of body weight of the human subject receiving the product ６ or more Tmem, about 4.0 x 10 per kilogram of body weight of the human subject receiving the product ６ or more Tmem, about 4.5 x 10 per kilogram of body weight of the human subject receiving the product ６ or more Tmem, about 5.0 x 10 per kilogram of body weight of the human subject receiving the product ６ or more Tmem, about 5.5 x 10 per kilogram of body weight of the human subject receiving the product ６ or more Tmem, about 6.0 x 10 per kilogram of body weight of the human subject receiving the product ６ or more Tmem, about 6.5 x 10 per kilogram of body weight of the human subject receiving the product ６ or more Tmem, about 7.0 x 10 per kilogram of body weight of the human subject receiving the product ６ or more Tmem, about 7.5 x 10 per kilogram of body weight of the human subject receiving the product ６ or more Tmem, about 8.0 x 10 per kilogram of body weight of the human subject receiving the product ６ or more Tmem, about 8.5 x 10 per kilogram of body weight of the human subject receiving the product ６ or more Tmem, about 9.0 x 10 per kilogram of body weight of the human subject receiving the product ６ or more Tmem, about 9.5 x 10 per kilogram of body weight of the human subject receiving the product ６ or more Tmem, about 1.0 x 10 per kilogram of body weight of the human subject receiving the product ７ or more Tmem, about 1.5 x 10 per kilogram of body weight of the human subject receiving the product ７ or more Tmem, about 2.0 x 10 per kilogram of body weight of the human subject receiving the product ７ or more Tmem, about 2.5 x 10 per kilogram of body weight of the human subject receiving the product ７ or more Tmem, about 3.0 x 10 per kilogram of body weight of the human subject receiving the product ７ or more Tmem, about 3.5 x 10 per kilogram of body weight of the human subject receiving the product ７ or more Tmem, about 4.0 x 10 per kilogram of body weight of the human subject receiving the product ７ or more Tmem, about 4.5 x 10 per kilogram of body weight of the human subject receiving the product ７ or more Tmem, about 5.0 x 10 per kilogram of body weight of the human subject receiving the product ７ or more Tmem, about 5.5 x 10 per kilogram of body weight of the human subject receiving the product ７ or more Tmem, about 6.0 x 10 per kilogram of body weight of the human subject receiving the product ７ or more Tmem, about 6.5 x 10 per kilogram of body weight of the human subject receiving the product ７ or more Tmem, about 7.0 x 10 per kilogram of body weight of the human subject receiving the product ７ or more Tmem, about 7.5 x 10 per kilogram of body weight of the human subject receiving the product ７ or more Tmem, about 8.0 x 10 per kilogram of body weight of the human subject receiving the product ７ or more Tmem, about 8.5 x 10 per kilogram of body weight of the human subject receiving the product ７ or more Tmem, about 9.0 x 10 per kilogram of body weight of the human subject receiving the product ７ or more Tmem, about 9.5 x 10 per kilogram of body weight of the human subject receiving the product ７ or more than about 1.0 x 10 Tmem per kilogram of body weight of the human subject receiving the product. ８ and / or d) the dose of Tmem is about 5.0 x 10 ５ Tmem or more, approximately 6.0 × 10 ５ Tmem or more, approximately 7.0 × 10 ５ More than 8.0 × 10 T ５ More than 10 Tmem, approximately 9.0 × 10 ５ 1.0×10 or more Tmem ６ More than 1.5 × 10 Tmem ６ More than 10 Tmem, approximately 2.0 × 10 ６ More than 10 Tmem, approximately 2.5 × 10 ６ More than 10 Tmem, approximately 3.0 × 10 ６ More than 10 Tmem, approximately 3.5 × 10 ６ Tmem or more, approximately 4.0 × 10 ６ More than 10 Tmem, approximately 4.5 × 10 ６ Tmem or more, approximately 5.0 × 10 ６ More than 5.5×10 Tmem ６ Tmem or more, approximately 6.0 × 10 ６ More than 6.5 × 10 Tmem ６ Tmem or more, approximately 7.0 × 10 ６ More than 7.5 × 10 Tmem ６ More than 8.0 × 10 T ６ More than 8.5 × 10 Tmem ６ More than 10 Tmem, approximately 9.0 × 10 ６ More than 9.5 × 10 Tmem ６ 1.0×10 or more Tmem ７ More than 1.5 × 10 Tmem ７ More than 10 Tmem, approximately 2.0 × 10 ７ More than 10 Tmem, approximately 2.5 × 10 ７ More than 10 Tmem, approximately 3.0 × 10 ７ More than 10 Tmem, approximately 3.5 × 10 ７ Tmem or more, approximately 4.0 × 10 ７ More than 10 Tmem, approximately 4.5 × 10 ７ Tmem or more, approximately 5.0 × 10 ７ More than 5.5×10 Tmem ７ Tmem or more, approximately 6.0 × 10 ７ More than 6.5 × 10 Tmem ７ Tmem or more, approximately 7.0 × 10 ７ More than 7.5 × 10 Tmem ７ More than 8.0 × 10 T ７ More than 8.5 × 10 Tmem ７ More than 10 Tmem, approximately 9.0 × 10 ７ More than 9.5 × 10 Tmem ７ 1.0×10 or more Tmem ８ More than 1.5 × 10 Tmem ８ More than 10 Tmem, approximately 2.0 × 10 ８ More than 10 Tmem, approximately 2.5 × 10 ８ More than 10 Tmem, approximately 3.0 × 10 ８ More than 10 Tmem, approximately 3.5 × 10 ８ Tmem or more, approximately 4.0 × 10 ８ More than 10 Tmem, approximately 4.5 × 10 ８ Tmem or more, approximately 5.0 × 10 ８ More than 5.5×10 Tmem ８ Tmem or more, approximately 6.0 × 10 ８ More than 6.5 × 10 Tmem ８ Tmem or more, approximately 7.0 × 10 ８ More than 7.5 × 10 Tmem ８ More than 8.0 × 10 T ８ More than 8.5 × 10 Tmem ８ More than 10 Tmem, approximately 9.0 × 10 ８ More than 9.5 × 10 Tmem ８ 1.0×10 or more Tmem ９ More than 1.5 × 10 Tmem ９ More than 10 Tmem, approximately 2.0 × 10 ９ More than 10 Tmem, approximately 2.5 × 10 ９ More than 10 Tmem, approximately 3.0 × 10 ９ More than 10 Tmem, approximately 3.5 × 10 ９ Tmem or more, approximately 4.0 × 10 ９ More than 10 Tmem, approximately 4.5 × 10 ９ Tmem or more, approximately 5.0 × 10 ９ More than 5.5×10 Tmem ９ Tmem or more, approximately 6.0 × 10 ９ More than 6.5 × 10 Tmem ９ Tmem or more, approximately 7.0 × 10 ９ More than 7.5 × 10 Tmem ９ More than 8.0 × 10 T ９ More than 8.5 × 10 Tmem ９ More than 10 Tmem, approximately 9.0 × 10 ９ More than 9.5 × 10 Tmem ９ 1.0×10 or more Tmem １０ 10 or more Tmem, or about 1.5 x 10 １０ and / or e) the dose of fresh Tregs is about 1.0 x 10 per kilogram of body weight of the human subject receiving the product ５ or more fresh Tregs, about 2.0 x 10 per kilogram of body weight of the human subject receiving the product ５ or more fresh Tregs, about 3.0 x 10 per kilogram of body weight of the human subject receiving the product ５ or more fresh Tregs, about 4.0 x 10 per kilogram of body weight of the human subject receiving the product ５ or more fresh Tregs, about 5.0 x 10 per kilogram of body weight of the human subject receiving the product ５ or more fresh Tregs, about 6.0 x 10 per kilogram of body weight of the human subject receiving the product ５ or more fresh Tregs, about 7.0 x 10 per kilogram of body weight of the human subject receiving the product ５ or more fresh Tregs, about 8.0 x 10 per kilogram of body weight of the human subject receiving the product ５ or more fresh Tregs, about 9.0 x 10 per kilogram of body weight of the human subject receiving the product ５ or more fresh Tregs, about 1.0 x 10 per kilogram of body weight of the human subject receiving the product ６ or more fresh Tregs, about 1.5 x 10 per kilogram of body weight of the human subject receiving the product ６ or more fresh Tregs, about 2.0 x 10 per kilogram of body weight of the human subject receiving the product ６ or more fresh Tregs, about 2.5 x 10 per kilogram of body weight of the human subject receiving the product ６ or more fresh Tregs, about 3.0 x 10 per kilogram of body weight of the human subject receiving the product ６ or more fresh Tregs, about 3.5 x 10 per kilogram of body weight of the human subject receiving the product ６ or more fresh Tregs, about 4.0 x 10 per kilogram of body weight of the human subject receiving the product ６ or more fresh Tregs, about 4.5 x 10 per kilogram of body weight of the human subject receiving the product ６ or more fresh Tregs, about 5.0 x 10 per kilogram of body weight of the human subject receiving the product ６ or more fresh Tregs, about 5.5 x 10 per kilogram of body weight of the human subject receiving the product ６ or more fresh Tregs, about 6.0 x 10 per kilogram of body weight of the human subject receiving the product ６ or more fresh Tregs, about 6.5 x 10 per kilogram of body weight of the human subject receiving the product ６ or more fresh Tregs, about 7.0 x 10 per kilogram of body weight of the human subject receiving the product ６ or more fresh Tregs, about 7.5 x 10 per kilogram of body weight of the human subject receiving the product ６ or more fresh Tregs, about 8.0 x 10 per kilogram of body weight of the human subject receiving the product ６ or more fresh Tregs, about 8.5 x 10 per kilogram of body weight of the human subject receiving the product ６ or more fresh Tregs, about 9.0 x 10 per kilogram of body weight of the human subject receiving the product ６ or more fresh Tregs, about 9.5 x 10 per kilogram of body weight of the human subject receiving the product ６ or more fresh Tregs, about 1.0 x 10 per kilogram of body weight of the human subject receiving the product ７ or more fresh Tregs, about 1.5 x 10 per kilogram of body weight of the human subject receiving the product ７ or more than about 2.0 x 10 fresh Tregs per kilogram of body weight of the human subject receiving the product. ７ and / or f) the dose of fresh Tregs is about 5.0 x 10 ５ fresh Tregs, approximately 6.0 x 10 ５ fresh Tregs, approximately 7.0 x 10 ５ fresh Tregs, approximately 8.0 x 10 ５ fresh Tregs, approximately 9.0 x 10 ５ fresh Tregs, approximately 1.0 x 10 ６ fresh Tregs, approximately 1.5 x 10 ６ fresh Tregs, approximately 2.0 x 10 ６ fresh Tregs, approximately 2.5 x 10 ６ fresh Tregs, approximately 3.0 x 10 ６ fresh Tregs, approximately 3.5 x 10 ６ fresh Tregs, approximately 4.0 x 10 ６ fresh Tregs, approximately 4.5 x 10 ６ fresh Tregs, approximately 5.0 x 10 ６ fresh Tregs, approximately 5.5 x 10 ６ fresh Tregs, approximately 6.0 x 10 ６ fresh Tregs, approximately 6.5 x 10 ６ fresh Tregs, approximately 7.0 x 10 ６ fresh Tregs, approximately 7.5 x 10 ６ fresh Tregs, approximately 8.0 x 10 ６ fresh Tregs, approximately 8.5 x 10 ６ fresh Tregs, approximately 9.0 x 10 ６ fresh Tregs, approximately 9.5 x 10 ６ fresh Tregs, approximately 1.0 x 10 ７ fresh Tregs, approximately 1.5 x 10 ７ fresh Tregs, approximately 2.0 x 10 ７ fresh Tregs, approximately 2.5 x 10 ７ fresh Tregs, approximately 3.0 x 10 ７ fresh Tregs, approximately 3.5 x 10 ７ fresh Tregs, approximately 4.0 x 10 ７ fresh Tregs, approximately 4.5 x 10 ７ fresh Tregs, approximately 5.0 x 10 ７ fresh Tregs, approximately 5.5 x 10 ７ fresh Tregs, approximately 6.0 x 10 ７ fresh Tregs, approximately 6.5 x 10 ７ fresh Tregs, approximately 7.0 x 10 ７ fresh Tregs, approximately 7.5 x 10 ７ fresh Tregs, approximately 8.0 x 10 ７ fresh Tregs, approximately 8.5 x 10 ７ fresh Tregs, approximately 9.0 x 10 ７ fresh Tregs, approximately 9.5 x 10 ７ fresh Tregs, approximately 1.0 x 10 ８ fresh Tregs, approximately 1.5 x 10 ８ fresh Tregs, approximately 2.0 x 10 ８ fresh Tregs, approximately 2.5 x 10 ８ fresh Tregs, approximately 3.0 x 10 ８ fresh Tregs, approximately 3.5 x 10 ８ fresh Tregs, approximately 4.0 x 10 ８ fresh Tregs, approximately 4.5 x 10 ８ fresh Tregs, approximately 5.0 x 10 ８ fresh Tregs, approximately 5.5 x 10 ８ fresh Tregs, approximately 6.0 x 10 ８ fresh Tregs, approximately 6.5 x 10 ８ fresh Tregs, approximately 7.0 x 10 ８ fresh Tregs, approximately 7.5 x 10 ８ fresh Tregs, approximately 8.0 x 10 ８ fresh Tregs, approximately 8.5 x 10 ８ fresh Tregs, approximately 9.0 x 10 ８ fresh Tregs, approximately 9.5 x 10 ８ fresh Tregs, approximately 1.0 x 10 ９ fresh Tregs, approximately 1.5 x 10 ９ fresh Tregs, approximately 2.0 x 10 ９ fresh Tregs, approximately 2.5 x 10 ９ fresh Tregs or approximately 3.0 x 10 ９ and / or g) the cell therapy product is administered in an amount of about 5.0 x 10 cells per kilogram of body weight of the human subject receiving the product. ５ less than about 4.5 x 10 per kilogram of body weight of the human subject receiving the product ５ less than about 4.0 x 10 per kilogram of body weight of the human subject receiving the product ５ less than about 3.5 x 10 per kilogram of body weight of the human subject receiving the product ５ less than about 3.0 x 10 T per kilogram of body weight of the human subject receiving the product ５ less than about 2.5 x 10 per kilogram of body weight of the human subject receiving the product ５ less than about 2.0 x 10 per kilogram of body weight of the human subject receiving the product ５ less than about 1.5 x 10 per kilogram of body weight of the human subject receiving the product ５ less than about 1.0 x 10 per kilogram of body weight of the human subject receiving the product ５ less than about 9.5 x 10 T per kilogram of body weight of the human subject receiving the product ４ less than about 9.0 x 10 T per kilogram of body weight of the human subject receiving the product ４ less than about 8.5 x 10 per kilogram of body weight of the human subject receiving the product ４ less than about 8.0 x 10 T per kilogram of body weight of the human subject receiving the product ４ less than about 7.5 x 10 per kilogram of body weight of the human subject receiving the product ４ less than about 7.0 x 10 T per kilogram of body weight of the human subject receiving the product ４ less than about 6.5 x 10 per kilogram of body weight of the human subject receiving the product ４ less than about 6.0 x 10 per kilogram of body weight of the human subject receiving the product ４ less than about 5.5 x 10 per kilogram of body weight of the human subject receiving the product ４ less than about 5.0 x 10 T per kilogram of body weight of the human subject receiving the product ４ less than about 4.5 x 10 per kilogram of body weight of the human subject receiving the product ４ less than about 4.0 x 10 per kilogram of body weight of the human subject receiving the product ４ less than about 3.5 x 10 per kilogram of body weight of the human subject receiving the product ４ less than about 3.0 x 10 T per kilogram of body weight of the human subject receiving the product ４ less than about 2.5 x 10 per kilogram of body weight of the human subject receiving the product ４ less than about 2.0 x 10 per kilogram of body weight of the human subject receiving the product ４ less than about 1.5 x 10 per kilogram of body weight of the human subject receiving the product ４ less than about 1.0 x 10 per kilogram of body weight of the human subject receiving the product ４ less than about 9.5 x 10 T per kilogram of body weight of the human subject receiving the product ３ less than about 9.0 x 10 T per kilogram of body weight of the human subject receiving the product ３ less than about 8.5 x 10 per kilogram of body weight of the human subject receiving the product ３ less than about 8.0 x 10 T per kilogram of body weight of the human subject receiving the product ３ less than about 7.5 x 10 per kilogram of body weight of the human subject receiving the product ３ less than about 7.0 x 10 T per kilogram of body weight of the human subject receiving the product ３ less than about 6.5 x 10 per kilogram of body weight of the human subject receiving the product ３ less than about 6.0 x 10 per kilogram of body weight of the human subject receiving the product ３ less than about 5.5 x 10 per kilogram of body weight of the human subject receiving the product ３ less than about 5.0 x 10 T per kilogram of body weight of the human subject receiving the product ３ less than about 4.5 x 10 per kilogram of body weight of the human subject receiving the product ３ less than about 4.0 x 10 per kilogram of body weight of the human subject receiving the product ３ less than about 3.5 x 10 per kilogram of body weight of the human subject receiving the product ３ less than about 3.0 x 10 T per kilogram of body weight of the human subject receiving the product ３ less than about 2.5 x 10 per kilogram of body weight of the human subject receiving the product ３ less than about 2.0 x 10 per kilogram of body weight of the human subject receiving the product ３ less than about 1.5 x 10 per kilogram of body weight of the human subject receiving the product ３ or less than about 1.0 x 10 per kilogram of body weight of the human subject receiving the product. ３ contains fewer than Tcon; and / or h) the cell therapy product is about 6.0 x 10 ７ Total Tcon less than about 5.5 x 10 ７ Total Tcon less than about 5.0 x 10 ７ Total Tcon less than 4.5 x 10 ７ Total Tcon less than about 4.0 x 10 ７ Total Tcon less than 3.5 x 10 ７ Total Tcon less than about 3.0 x 10 ７ Total Tcon less than about 2.5 x 10 ７ Total Tcon less than about 2.0 x 10 ７ Total Tcon less than about 1.5 x 10 ７ Total Tcon less than about 1.0 x 10 ７ Total Tcon less than about 9.5 x 10 ６ Total Tcon of less than about 9.0 x 10 ６ Total Tcon less than about 8.5 x 10 ６ Total Tcon less than about 8.0 x 10 ６ Total Tcon less than about 7.5 x 10 ６ Total Tcon less than about 7.0 x 10 ６ Total Tcon less than about 6.5 x 10 ６ Total Tcon less than about 6.0 x 10 ６ Total Tcon less than about 5.5 x 10 ６ Total Tcon less than about 5.0 x 10 ６ Total Tcon less than 4.5 x 10 ６ Total Tcon less than about 4.0 x 10 ６ Total Tcon less than 3.5 x 10 ６ Total Tcon less than about 3.0 x 10 ６ Total Tcon less than about 2.5 x 10 ６ Total Tcon less than about 2.0 x 10 ６ Total Tcon less than about 1.5 x 10 ６ A total Tcon of less than 1.0 x 10 ６ including less than 10 total Tcon, The cell therapy product of claim 1.

3. a) the isolated CD45 ＋ the population of cells is formulated in a volume ranging from about 5 mL to about 1 L; and / or b) the isolated CD45 ＋ The cell population may be about 5 mL, about 10 mL, about 15 mL, about 20 mL, about 25 mL, about 30 mL, about 35 mL, about 40 mL, about 45 mL, about 50 mL, about 55 mL, about 60 mL, about 65 mL, about 70 mL, about 75 mL, about 80 mL, about 85 mL, about 90 mL, about 95 mL, about 100 mL, about 125 mL, about 150 mL, about 175 mL, about 200 mL, about 225 mL, about 250 mL, about 275 mL, about 300 mL, about 325 mL, about 350 mL, about 375 mL, about 400 mL, about 450 mL, about 500 mL, about 550 mL, about 600 mL, about 650 mL, about 700 mL, about 750 mL, about 800 mL, about 850 mL, about 900 mL, about 950 mL, about 1000 mL, about 1250 mL, about 1500 mL, about 1750 mL, about 2000 mL, about 2250 mL, about 2500 mL, about 2750 mL, about 3000 mL, about 3250 mL, about 3500 mL, about 3750 mL, about 4000 mL, about 45 ... and / or is formulated in a volume of 5 mL, about 400 mL, about 425 mL, about 450 mL, about 475 mL, about 500 mL, about 525 mL, about 550 mL, about 575 mL, about 600 mL, about 625 mL, about 650 mL, about 675 mL, about 700 mL, about 725 mL, about 750 mL, about 775 mL, about 800 mL, about 825 mL, about 850 mL, about 875 mL, about 900 mL, about 925 mL, about 950 mL, about 975 mL, or about 1 L; and / or c) the neutral pH is in the range of about 6.8 to about 7.6; and / or d) the excipient comprises a transport buffer, optionally comprising about 120 to about 160 mEq sodium, and / or the transport buffer comprising a total of about 270 to about 320 mOsmol / L, optionally the transport buffer is selected from the group consisting of phosphate buffered saline (PBS), human serum, Plasmalyte, Normosol-R, and any combination thereof, optionally the transport buffer further comprises about 0.1% v / v to about 10% v / v of a human carrier protein, optionally the human carrier protein is selected from the group consisting of human serum albumin (HSA), intravenous immunoglobulin (IVIG), AB serum, and any combination thereof; and / or e) the isolated CD45 ＋ the population of cells is formulated in a single-dose transfer bag, optionally said single-dose transfer bag being a polyvinyl chloride (PVC) transfer bag or an ethylene vinyl acetate (EVA) transfer bag; and / or f) the isolated CD45 ＋ the population of cells is enriched for HSPCs, Tmems, and Tregs; and / or g) the isolated CD45 ＋ The cell population is less than 1:3, less than 1:5, less than 1:10, less than 1:20, less than 1:30, less than 1:40, less than 1:50, less than 1:60, less than 1:70, less than 1:80, less than 1:90, less than 1:100, less than 1:200, less than 1:300, less than 1:400, less than 1:500, less than 1:600, less than 1:700, less than 1:800, less than 1:900, less than 1:1,000, less than 1:1,500 Less than 0, Less than 1:2,000, Less than 1:2,500, Less than 1:3,000, Less than 1:3,500, Less than 1:4,000, Less than 1:4,500, Less than 1:5,000, Less than 1:5,500, Less than 1:6,000, Less than 1:6,500, Less than 1:7,000, Less than 1:7,500, Less than 1:8,000, Less than 1:8,500, Less than 1:9,000, Less than 1:9,500, Less than 1:10,000 less than 1:15,000, less than 1:20,000, less than 1:25,000, less than 1:30,000, less than 1:35,000, less than 1:40,000, less than 1:45,000, less than 1:50,000, less than 1:55,000, less than 1:60,000, less than 1:65,000, less than 1:70,000, less than 1:75,000, less than 1:80,000, less than 1:85,000, and / or comprising a ratio of Tcon to HSPC of less than 1:90,000, less than 1:95,000, less than 1:100,000, less than 1:200,000, less than 1:300,000, less than 1:400,000, less than 1:500,000, less than 1:600,000, less than 1:700,000, less than 1:800,000, less than 1:900,000, or less than 1:1,000,000; and / or h) the isolated CD45 ＋ The population of cells is less than 1:10, less than 1:20, less than 1:30, less than 1:40, less than 1:50, less than 1:60, less than 1:70, less than 1:80, less than 1:90, less than 1:100, less than 1:200, less than 1:300, less than 1:400, less than 1:500, less than 1:600, less than 1:700, less than 1:800, less than 1:900, less than 1:1,000, less than 1:1,500, less than 1:2,000, less than 1:2,500, less than 1:3,000, less than 1:3,500, less than 1:4,000, less than 1:4,500, less than 1: and / or comprising a ratio of Tcon to Tmem of less than 5,000, less than 1:5,500, less than 1:6,000, less than 1:6,500, less than 1:7,000, less than 1:7,500, less than 1:8,000, less than 1:8,500, less than 1:9,000, less than 1:9,500, less than 1:10,000, less than 1:15,000, less than 1:20,000, less than 1:25,000, less than 1:30,000, less than 1:35,000, less than 1:40,000, less than 1:45,000, or less than 1:50,000; and / or i) the isolated CD45 ＋ The population of cells is less than 1:1, less than 1:2, less than 1:3, less than 1:4, less than 1:5, less than 1:6, less than 1:7, less than 1:8, less than 1:9, less than 1:10, less than 1:11, less than 1:12, less than 1:13, less than 1:14, less than 1:15, less than 1:16, less than 1:17, less than 1:18, less than 1:19, less than 1:20, less than 1:30, less than 1:40, less than 1:50, less than 1:60, less than 1:70, less than 1:80, less than 1:90, less than 1:100, less than 1:200, less than 1:300, less than 1:400, less than 1:500, less than 1:600, less than 1:700, less than 1:800, less than 1:900, less than 1:1,000, less than 1:1,500, less than 1:2 ,000, Less than 1:2,500, Less than 1:3,000, Less than 1:3,500, Less than 1:4,000, Less than 1:4,500, Less than 1:5,000, Less than 1:5,500, Less than 1:6,000, Less than 1:6,500, Less than 1:7,000, Less than 1:7,500, Less than 1:8,000, Less than 1:8,500, Less than 1:9, and / or comprising a Tcon to Treg ratio of less than 1:000, less than 1:9,500, less than 1:10,000, less than 1:15,000, less than 1:20,000, less than 1:25,000, less than 1:30,000, less than 1:35,000, less than 1:40,000, less than 1:45,000, or less than 1:50,000; and / or j) the isolated CD45 ＋ the population of cells comprises a ratio of HSPCs to Tmems of about 500:1 to about 1:1,000; and / or k) the isolated CD45 ＋ the population of cells comprises a ratio of HSPCs to Tregs of about 100:1 to about 1:30; and / or l) the isolated CD45 ＋ the population of cells comprises a Tmem to Treg ratio of about 2000:1 to about 1:10; and / or m) the isolated CD45 ＋ A population of cells expressing TCR Vα24Jα18 ＋ CD127 ＋ and optionally, said isolated CD45 ＋ The population of cells is about 5.0 x 10 per kilogram of body weight of the human subject receiving the product. ２ ~Approx. 2.0×10 ６ a dose of iNKT, or approximately 2.0 x 10 ３ ~Approx. 4.0×10 ８ and optionally, the dose of iNKT is about 5.0 x 10 per kilogram of body weight of the human subject receiving the product. ２ or more iNKTs, about 6.0 x 10 per kilogram of body weight of said human subject receiving said product ２ or more iNKTs, about 7.0 x 10 per kilogram of body weight of said human subject receiving said product ２ or more iNKTs, about 8.0 x 10 per kilogram of body weight of said human subject receiving said product ２ or more iNKTs, about 9.0 x 10 per kilogram of body weight of said human subject receiving said product ２ or more iNKTs, about 1.0 x 10 per kilogram of body weight of said human subject receiving said product ３ or more iNKTs, about 2.0 x 10 per kilogram of body weight of said human subject receiving said product ３ or more iNKTs, about 3.0 x 10 per kilogram of body weight of said human subject receiving said product ３ or more iNKTs, about 4.0 x 10 per kilogram of body weight of said human subject receiving said product ３ or more iNKTs, about 5.0 x 10 per kilogram of body weight of said human subject receiving said product ３ or more iNKTs, about 6.0 x 10 per kilogram of body weight of said human subject receiving said product ３ or more iNKTs, about 7.0 x 10 per kilogram of body weight of said human subject receiving said product ３ or more iNKTs, about 8.0 x 10 per kilogram of body weight of said human subject receiving said product ３ or more iNKTs, about 9.0 x 10 per kilogram of body weight of said human subject receiving said product ３ or more iNKTs, about 1.0 x 10 per kilogram of body weight of said human subject receiving said product ４ or more iNKTs, about 2.0 x 10 per kilogram of body weight of said human subject receiving said product ４ or more iNKTs, about 3.0 x 10 per kilogram of body weight of said human subject receiving said product ４ or more iNKTs, about 4.0 x 10 per kilogram of body weight of said human subject receiving said product ４ or more iNKTs, about 5.0 x 10 per kilogram of body weight of said human subject receiving said product ４ or more iNKTs, about 6.0 x 10 per kilogram of body weight of said human subject receiving said product ４ or more iNKTs, about 7.0 x 10 per kilogram of body weight of said human subject receiving said product ４ or more iNKTs, about 8.0 x 10 per kilogram of body weight of said human subject receiving said product ４ or more iNKTs, about 9.0 x 10 per kilogram of body weight of said human subject receiving said product ４ or more iNKTs, about 1.0 x 10 per kilogram of body weight of said human subject receiving said product ５ or more iNKTs, about 2.0 x 10 per kilogram of body weight of said human subject receiving said product ５ or more iNKTs, about 3.0 x 10 per kilogram of body weight of said human subject receiving said product ５ or more iNKTs, about 4.0 x 10 per kilogram of body weight of said human subject receiving said product ５ or more iNKTs, about 5.0 x 10 per kilogram of body weight of said human subject receiving said product ５ or more iNKTs, about 6.0 x 10 per kilogram of body weight of said human subject receiving said product ５ or more iNKTs, about 7.0 x 10 per kilogram of body weight of said human subject receiving said product ５ or more iNKTs, about 8.0 x 10 per kilogram of body weight of said human subject receiving said product ５ or more iNKTs, about 9.0 x 10 per kilogram of body weight of said human subject receiving said product ５ or more iNKTs, about 1.0 x 10 per kilogram of body weight of said human subject receiving said product ６ or more iNKTs, about 1.5 x 10 per kilogram of body weight of said human subject receiving said product ６ or more than about 2.0 x 10 iNKTs per kilogram of body weight of said human subject receiving said product. ６ or more doses of iNKT, optionally wherein said dose of iNKT is about 2.0 x 10 ３ More than 3.0 x 10 iNKTs ３ More than 4.0 x 10 iNKTs ３ More than 5.0 x 10 iNKTs ３ More than 6.0 x 10 iNKTs ３ More than 7.0 x 10 iNKTs ３ More than 8.0 x 10 iNKTs ３ More than 9.0 x 10 iNKTs ３ More than 1.0 x 10 iNKTs ４ More than 2.0 x 10 iNKTs ４ More than 3.0 x 10 iNKTs ４ More than 4.0 x 10 iNKTs ４ More than 5.0 x 10 iNKTs ４ More than 6.0 x 10 iNKTs ４ More than 7.0 x 10 iNKTs ４ More than 8.0 x 10 iNKTs ４ More than 9.0 x 10 iNKTs ４ More than 1.0 x 10 iNKTs ５ More than 2.0 x 10 iNKTs ５ More than 3.0 x 10 iNKTs ５ More than 4.0 x 10 iNKTs ５ More than 5.0 x 10 iNKTs ５ More than 6.0 x 10 iNKTs ５ More than 7.0 x 10 iNKTs ５ More than 8.0 x 10 iNKTs ５ More than 9.0 x 10 iNKTs ５ More than 1.0 x 10 iNKTs ６ More than 1.5 x 10 iNKTs ６ More than 2.0 x 10 iNKTs ６ More than 2.5 x 10 iNKTs ６ More than 3.0 x 10 iNKTs ６ More than 3.5 x 10 iNKTs ６ More than 4.0 x 10 iNKTs ６ More than 4.5 x 10 iNKTs ６ More than 5.0 x 10 iNKTs ６ More than 5.5 x 10 iNKTs ６ More than 6.0 x 10 iNKTs ６ More than 6.5 x 10 iNKTs ６ More than 7.0 x 10 iNKTs ６ More than 7.5 x 10 iNKTs ６ More than 8.0 x 10 iNKTs ６ More than 8.5 x 10 iNKTs ６ More than 9.0 x 10 iNKTs ６ More than 9.5 x 10 iNKTs ６ More than 1.0 x 10 iNKTs ７ More than 1.5 x 10 iNKTs ７ More than 2.0 x 10 iNKTs ７ More than 2.5 x 10 iNKTs ７ More than 3.0 x 10 iNKTs ７ More than 3.5 x 10 iNKTs ７ More than 4.0 x 10 iNKTs ７ More than 4.5 x 10 iNKTs ７ More than 5.0 x 10 iNKTs ７ More than 5.5 x 10 iNKTs ７ More than 6.0 x 10 iNKTs ７ More than 6.5 x 10 iNKTs ７ More than 7.0 x 10 iNKTs ７ More than 7.5 x 10 iNKTs ７ More than 8.0 x 10 iNKTs ７ More than 8.5 x 10 iNKTs ７ More than 9.0 x 10 iNKTs ７ More than 9.5 x 10 iNKTs ７ More than 1.0 x 10 iNKTs ８ More than 1.5 x 10 iNKTs ８ More than 2.0 x 10 iNKTs ８ More than 2.5 x 10 iNKTs ８ More than 3.0 x 10 iNKTs ８ More than 3.5 x 10 iNKTs ８ or more iNKTs, or approximately 4.0 x 10 ８ and optionally, said isolated CD45 ＋ The population of cells comprises a ratio of HSPC to iNKT of about 1:2 to about 500,000:1, and optionally, the isolated CD45 ＋ The population of cells comprises an iNKT to Tcon ratio of less than 1:1, less than 1:2, less than 1:3, less than 1:4, less than 1:5, less than 1:6, less than 1:7, less than 1:8, less than 1:9, less than 1:10, less than 1:20, less than 1:30, less than 1:40, less than 1:50, less than 1:60, less than 1:70, less than 1:80, less than 1:90, or less than 1:100, and optionally, said isolated CD45 ＋ The population of cells comprises a ratio of iNKT to Tmem of about 5:1 to about 1:1,000,000, and optionally said iNKT is CD1d-tet ＋ , 6B11 ＋ , or CD1d-tet ＋ 6B11 ＋ and / or n) the HSPC is cKIT ＋ , CD133 ＋ , CD90 ＋ , CD38 － , CD45RA － , Lin － , CD19 － , TCRα － or any combination thereof, and / or o) the Tmem is CD3 ＋ CD45RO ＋ and / or p) The Tmem is a T central memory cell (T ＣＭ ), a population of T effector memory cells (T ＥＭ ) population, T stem center memory cells (T ＳＣＭ ), or any combination thereof, and optionally, ＣＭ is CD4 ＋ CD45RO ＋ or CD8 ＋ CD45RO ＋ and / or the T ＣＭ is CD45RA － , CD62L ＋ , CCR7 ＋ or any combination thereof, and optionally, ＥＭ is CD4 ＋ , CD45RO ＋ , CD45RA － , CD62L － , CCR7 － or any combination thereof, and optionally, ＳＣＭ is CD4 ＋ CD45RA ＋ or CD8 ＋ CD45RA ＋ and / or the T ＳＣＭ is CD95 ＋ , CD122 ＋ , CXCR3 ＋ , LFA-1 ＋ or any combination thereof, and / or q) The Treg is FoxP3 ＋ and / or r) the Tregs comprise a population of naive Treg cells, a population of memory Treg cells, or a population of naive and memory Treg cells, and optionally the naive Treg cells are CD4 ＋ CD25 ＋ CD127 ｄｉｍ FoxP3 ＋ CD45RA ＋ CD45RO － and optionally, the dose of Tregs is about 2.0 x 10 per kilogram of body weight of the human subject receiving the product. ５ ~Approx. 5.0×10 ８ a dose of naive Treg cells, or approximately 8.0 x 10 ５ ~Approx. 1.0×10 １１ a total dose of naive Treg cells, and optionally, the isolated CD45 ＋ The population of cells comprises a ratio of HSPCs to naive Tregs that is about 1:500 to about 100:1, and optionally, the isolated CD45 ＋ The population of cells comprises a ratio of Tmem to naive Treg of about 3:1 to about 1:10, and optionally, the isolated CD45 ＋ The population of cells comprises a ratio of Tcon to naive Treg of less than 1:1, less than 1:2, less than 1:3, less than 1:4, less than 1:5, less than 1:6, less than 1:7, less than 1:8, less than 1:9, or less than 1:10, and optionally said memory Treg cells are CD4 ＋ CD25 ＋ CD127 ｄｉｍ FoxP3 ＋ CD45RA － CD45RO ＋ and optionally, the dose of Tregs is about 5.0 x 10 per kilogram of body weight of the human subject receiving the product. ４ ~Approx. 5.0×10 ８ a dose of memory Treg cells, or about 2.0 x 10 ５ ~Approx. 1.0×10 １１ a total dose of memory Treg cells, and optionally, said isolated CD45 ＋ The population of cells comprises a ratio of HSPCs to memory Tregs of about 1:500 to about 10,000:1, and optionally, the isolated CD45 ＋ The population of cells comprises a ratio of Tmem to memory Treg of about 27:1 to about 9:10, and optionally, the isolated CD45 ＋ the population of cells comprises a ratio of Tcon to memory Treg of less than 1:1, less than 1:2, less than 1:3, less than 1:4, less than 1:5, less than 1:6, less than 1:7, less than 1:8, less than 1:9, less than 1:10, less than 1:20, less than 1:30, less than 1:40, less than 1:50, less than 1:60, less than 1:70, less than 1:80, less than 1:90, or less than 1:100; and / or s) the Tcon is TCRα ＋ , TCRβ ＋ , or TCRα ＋ TCRβ ＋ and / or said Tcon is CD25 － , CD127 ＋ , or CD25 － CD127 ＋ and / or said Tcon is TCRα ＋ TCRβ ＋ CD45RA ＋ CD45RO － CD25 － CD95 － IL-2Rβ － CD127 ＋ and / or t) the isolated CD45 ＋ the population of cells contains less than about 5 EU to less than about 0.5 EU endotoxin per mL of formulation; and / or u) the weight of the human subject receiving the product is an actual weight or the weight of the human subject receiving the product is an ideal weight; 3. The cell therapy product of claim 1 or 2.

4. the article of manufacture further comprises a pharmaceutical composition comprising one or more doses of a graft-versus-host disease (GVHD) prophylactic agent; Optionally, the GVHD prophylactic agent is tacrolimus; Optionally, one or more doses of tacrolimus are provided to maintain a trough blood level of about 5 ng / mL to about 10 ng / mL in said human subject receiving said product; Optionally, the pharmaceutical composition comprises tacrolimus at a dose ranging from about 0.01 mg per kilogram of body weight of the human subject receiving the product to about 0.50 mg per kilogram of body weight of the human subject receiving the product twice daily; Optionally, said tacrolimus is ＋ or about 150 days after administration of the population of cells, A cell therapy product according to any one of claims 1 to 3.

5. a) the HSPCs, the Tmems, the Tregs, or any combination thereof are obtained from an allogeneic donor that is HLA-matched relative to the human subject receiving the product, and / or the isolated CD45 ＋ the population of cells is derived from an allogeneic donor that is HLA-matched relative to the human subject receiving the product; or b) the HSPCs, the Tmems, the Tregs, or any combination thereof are obtained from an allogeneic donor with at least one HLA mismatch compared to the human subject receiving the product, and / or the isolated CD45 ＋ The population of cells is derived from an allogeneic donor with at least one HLA mismatch relative to the human subject receiving the product, and optionally, the at least one HLA mismatch is at an allele selected from the group consisting of HLA-A, HLA-B, HLA-C, HLA-DRB1, and any combination thereof, and optionally, the cells with at least one HLA mismatch are derived from a donor that is 6 / 8 HLA mismatched relative to the human subject receiving the product, or 7 / 8 HLA mismatched relative to the human subject receiving the product. The cells are derived from an HLA-mismatched donor, and optionally the cells with at least one HLA mismatch are derived from a donor that is 7 / 8 HLA-mismatched relative to the human subject receiving the product, and optionally the donor that is 7 / 8 HLA-mismatched relative to the human subject receiving the product has a mismatch in HLA-A, and optionally the donor that is 7 / 8 HLA-mismatched relative to the human subject receiving the product has a mismatch in HLA-B, and optionally the donor that is 7 / 8 HLA-mismatched relative to the human subject receiving the product. The donor who is a match has a mismatch at HLA-C, and optionally a 7 / 8 HLA mismatch compared to the human subject receiving the product, has a mismatch at HLA-DRB1, and optionally a donor who has at least one HLA mismatch compared to the human subject receiving the product because the donor is homozygous for the HLA allele but the human subject receiving the product is heterozygous for the HLA allele, and optionally a donor who is heterozygous for the HLA allele because the human subject receiving the product is heterozygous for the HLA allele. the donor having at least one HLA mismatch compared to the subject has a mismatched HLA allele because the donor is heterozygous for the HLA allele, but the human subject receiving the product is homozygous for the HLA allele; optionally, the donor having at least one HLA mismatch compared to the human subject receiving the product has a mismatched HLA allele because both the donor and the human subject receiving the product are heterozygous for the HLA allele; or c) the HSPCs, the Tmems, the Tregs, or any combination thereof are obtained from a half-matched allogeneic donor relative to the human subject receiving the product, or the isolated CD45 ＋ the population of cells is derived from a half-matched allogeneic donor relative to the human subject receiving the product; Optionally, the allogeneic donor is related to the human subject receiving the product, or the allogeneic donor is unrelated to the human subject receiving the product. A cell therapy product according to any one of claims 1 to 4.

6. below: a) a method of treating a human subject having or suspected of having a hematological malignancy, optionally wherein said hematological malignancy is selected from the group consisting of leukemia, acute leukemia, acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), mixed phenotype acute leukemia (MPAL), chronic myelogenous leukemia (CML), multiple myeloma, lymphoma, Hodgkin's lymphoma, non-Hodgkin's lymphoma, myelodysplastic syndrome (MDS), myeloproliferative syndrome, myelofibrosis, and blastic plasmacytoid dendritic cell neoplasm (BPDCN), optionally wherein said acute leukemia is in complete remission, and optionally wherein said acute leukemia is active acute leukemia; and / or b) A method of treating a human subject having or suspected of having an autoimmune disorder, optionally wherein the autoimmune disorder is multiple sclerosis, and optionally wherein the multiple sclerosis is primary progressive multiple sclerosis (PPMS). A cell therapy product according to any one of claims 1 to 5 for use in

7. 1. A method of treating a human subject, comprising: a) the human subject has or is suspected of having acute leukemia that is in complete remission, and the method comprises administering to the subject an isolated CD45 ＋ administering to said human subject a cell therapy product comprising a population of said isolated CD45 cells. ＋ The cell population is CD34 ＋ Enriched population of hematopoietic stem and progenitor cells (HSPCs), CD45RA － Enriched populations of memory T cells (Tmem) and fresh CD4 ＋ CD25 ＋ CD127 ｄｉｍ an enriched population of regulatory T cells (Tregs), and ＋ The population of cells is about 5.0 x 10 per kilogram of body weight of the human subject receiving the product. ５ < naive conventional CD3 ＋ CD25 － CD45RA ＋ T cells (Tcon), approximately 6.0 x 10 ７ Less than 100 total naive conventional CD3 ＋ CD25 － CD45RA ＋ T cells (Tcon), or approximately 1.0 x 10 ６ Less than 100 total naive conventional CD3 ＋ CD25 － CD45RA ＋ Naive conventional CD3 containing T cells (Tcon) ＋ CD25 － CD45RA ＋ T cells (Tcon) are depleted, Optionally, the human subject has a blast load of about 5% or less in their bone marrow, optionally, there are no circulating blasts and / or blasts with Auer rods in the human subject, optionally there is no extramedullary disease in the human subject, and optionally the human subject has a blast load of about 1.0 x 10 ９ / L or greater, and optionally the human subject has an absolute neutrophil count (ANC) of about 1.0 x 10 １１ / L or greater, optionally the human subject is red blood cell transfusion independent, and optionally the acute leukemia is in complete remission with incomplete hematologic recovery, and optionally the human subject has residual neutropenia, and optionally the human subject has a platelet count of about 1.0 x 10 ９ / L or less, and optionally the human subject has residual thrombocytopenia, and optionally the human subject has a blood count of about 1.0 x 10 １１ / L or less, or b) the human subject has or is suspected of having active acute leukemia, and the method comprises administering isolated CD45 ＋ administering to said human subject a cell therapy product comprising a population of said isolated CD45 cells. ＋ The cell population is CD34 ＋ Enriched population of hematopoietic stem and progenitor cells (HSPCs), CD45RA － Enriched populations of memory T cells (Tmem) and fresh CD4 ＋ CD25 ＋ CD127 ｄｉｍ an enriched population of regulatory T cells (Tregs), and ＋ The population of cells is about 5.0 x 10 per kilogram of body weight of the human subject receiving the product. ５ < naive conventional CD3 ＋ CD25 － CD45RA ＋ T cells (Tcon), approximately 6.0 x 10 ７ Less than 100 total naive conventional CD3 ＋ CD25 － CD45RA ＋ T cells (Tcon), or approximately 1.0 x 10 ６ Less than 100 total naive conventional CD3 ＋ CD25 － CD45RA ＋ Naive conventional CD3 containing T cells (Tcon) ＋ CD25 － CD45RA ＋ T cells (Tcon) are depleted, and optionally the human subject has a leukemic blast infiltration of about 10% or less of the bone marrow, and optionally the acute leukemia is acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), and / or mixed phenotype acute leukemia (MPAL), or c) the human subject has or is suspected of having chronic myeloid leukemia (CML), and the method comprises administering to the subject an isolated CD45 ＋ administering to said human subject a cell therapy product comprising a population of said isolated CD45 cells. ＋ The cell population is CD34 ＋ Enriched population of hematopoietic stem and progenitor cells (HSPCs), CD45RA － Enriched populations of memory T cells (Tmem) and fresh CD4 ＋ CD25 ＋ CD127 ｄｉｍ an enriched population of regulatory T cells (Tregs), and ＋ The population of cells is about 5.0 x 10 per kilogram of body weight of the human subject receiving the product. ５ < naive conventional CD3 ＋ CD25 － CD45RA ＋ T cells (Tcon), approximately 6.0 x 10 ７ Less than 100 total naive conventional CD3 ＋ CD25 － CD45RA ＋ T cells (Tcon), or approximately 1.0 x 10 ６ Less than 100 total naive conventional CD3 ＋ CD25 － CD45RA ＋ Naive conventional CD3 containing T cells (Tcon) ＋ CD25 － CD45RA ＋ T cells (Tcon) are depleted, and optionally the human subject is in a myeloblastic and / or lymphoblastic blast crisis, optionally the blastic crisis is in complete remission, optionally the blastic crisis is in complete remission with incomplete hematologic recovery, and optionally the CML is in accelerated phase, or the CML is in chronic phase, and optionally the chronic phase CML is resistant to or intolerant to one or more first or second generation tyrosine kinase inhibitors (TKIs), or d) the human subject has or is suspected of having high-risk or very high-risk myelodysplastic syndrome (MDS), and the method comprises administering isolated CD45 ＋ administering to said human subject a cell therapy product comprising a population of said isolated CD45 cells. ＋ The cell population is CD34 ＋ Enriched population of hematopoietic stem and progenitor cells (HSPCs), CD45RA － Enriched populations of memory T cells (Tmem) and fresh CD4 ＋ CD25 ＋ CD127 ｄｉｍ an enriched population of regulatory T cells (Tregs), and ＋ The population of cells is about 5.0 x 10 per kilogram of body weight of the human subject receiving the product. ５ < naive conventional CD3 ＋ CD25 － CD45RA ＋ T cells (Tcon), approximately 6.0 x 10 ７ Less than 100 total naive conventional CD3 ＋ CD25 － CD45RA ＋ T cells (Tcon), or approximately 1.0 x 10 ６ Less than 100 total naive conventional CD3 ＋ CD25 － CD45RA ＋ Naive conventional CD3 containing T cells (Tcon) ＋ CD25 － CD45RA ＋ T cells (Tcon) are depleted, and optionally the human subject has a blast load of about 10% or less in their bone marrow; or e) the human subject has or is suspected of having myelofibrosis, and the method comprises administering to the subject an isolated CD45 ＋ administering to said human subject a cell therapy product comprising a population of said isolated CD45 cells. ＋ The cell population is CD34 ＋ Enriched population of hematopoietic stem and progenitor cells (HSPCs), CD45RA － Enriched populations of memory T cells (Tmem) and fresh CD4 ＋ CD25 ＋ CD127 ｄｉｍ an enriched population of regulatory T cells (Tregs), and ＋ The population of cells is about 5.0 x 10 per kilogram of body weight of the human subject receiving the product. ５ < naive conventional CD3 ＋ CD25 － CD45RA ＋ T cells (Tcon), approximately 6.0 x 10 ７ Less than 100 total naive conventional CD3 ＋ CD25 － CD45RA ＋ T cells (Tcon), or approximately 1.0 x 10 ６ Less than 100 total naive conventional CD3 ＋ CD25 － CD45RA ＋ Naive conventional CD3 containing T cells (Tcon) ＋ CD25 － CD45RA ＋ T cells (Tcon) are depleted, and optionally the myelofibrosis is eligible for standard myeloablative allogeneic hematopoietic stem cell transplantation (alloHSCT), and optionally the myelofibrosis is intermediate-2 risk or high-risk myelofibrosis, and optionally the myelofibrosis is intermediate-1 risk myelofibrosis associated with high symptom burden, low platelet count, and / or complex cytogenetics. method.

8. a) the method further comprises administering one or more doses of a graft-versus-host disease (GVHD) prophylactic agent, optionally wherein the GVHS prophylactic agent is tacrolimus, optionally wherein the tacrolimus is provided in an amount sufficient to maintain a trough blood level of about 5 ng / mL to about 10 ng / mL in the human subject, optionally wherein the tacrolimus is provided twice daily at a dose ranging from about 0.01 mg per kilogram of body weight of the human subject to about 0.50 mg per kilogram of body weight of the human subject, optionally wherein the tacrolimus inhibits CD45 ＋ or about 20 days or more, about 25 days or more, about 30 days or more, about 35 days or more, about 40 days or more, about 55 days or more, about 50 days or more, about 55 days or more, about 60 days or more, about 65 days or more, about 770 days or more, about 75 days or more, about 80 days or more, about 85 days or more, about 90 days or more, about 95 days or more, about 100 days or more, about 110 days or more, about 120 days or more, about 130 days or more, about 140 days or more, or about 1 in an amount to maintain or maintain a target blood level of about 1 ng / mL to about 10 ng / mL in the human subject for 50 days, optionally wherein the tacrolimus is initially administered between about 12 hours and 24 hours after administration of the cell therapy product, and optionally wherein the administration of the tacrolimus begins to taper about 90 days after the initial administration of the tacrolimus; and / or b) said administering comprises administering to said isolated CD45 ＋ injecting a population of cells into said human subject; and / or c) the isolated CD45 ＋ the population of cells is about 1.0 x 10 per kilogram of body weight of said human subject ５ ~Approx. 1.0×10 ８ HSPCs, or approximately 5.0 x 10 ５ ~Approx. 1.5×10 １０ HSPCs; and / or d) the isolated CD45 ＋ the population of cells is about 1.0 x 10 per kilogram of body weight of said human subject ５ or more than about 2.0 x 10 HSPCs per kilogram of body weight of the human subject ５ or more than about 3.0 x 10 HSPCs per kilogram of body weight of the human subject ５ or more than about 4.0 x 10 HSPCs per kilogram of body weight of the human subject ５ or more than about 5.0 x 10 HSPCs per kilogram of body weight of the human subject ５ or more than about 6.0 x 10 HSPCs per kilogram of body weight of the human subject ５ or more than about 7.0 x 10 HSPCs per kilogram of body weight of the human subject ５ or more than about 8.0 x 10 HSPCs per kilogram of body weight of the human subject ５ or more than about 9.0 x 10 HSPCs per kilogram of body weight of the human subject ５ or more than about 1.0 x 10 HSPCs per kilogram of body weight of the human subject ６ or more than about 1.5 x 10 HSPCs per kilogram of body weight of the human subject ６ or more than about 2.0 x 10 HSPCs per kilogram of body weight of the human subject ６ or more than about 2.5 x 10 HSPCs per kilogram of body weight of the human subject ６ or more than about 3.0 x 10 HSPCs per kilogram of body weight of the human subject ６ or more than about 3.5 x 10 HSPCs per kilogram of body weight of the human subject ６ or more than about 4.0 x 10 HSPCs per kilogram of body weight of the human subject ６ or more than about 4.5 x 10 HSPCs per kilogram of body weight of the human subject ６ or more than about 5.0 x 10 HSPCs per kilogram of body weight of the human subject ６ or more than about 5.5 x 10 HSPCs per kilogram of body weight of the human subject ６ or more than about 6.0 x 10 HSPCs per kilogram of body weight of the human subject ６ or more than about 6.5 x 10 HSPCs per kilogram of body weight of the human subject ６ or more than about 7.0 x 10 HSPCs per kilogram of body weight of the human subject ６ or more than about 7.5 x 10 HSPCs per kilogram of body weight of the human subject ６ or more than about 8.0 x 10 HSPCs per kilogram of body weight of the human subject ６ or more than about 8.5 x 10 HSPCs per kilogram of body weight of the human subject ６ or more than about 9.0 x 10 HSPCs per kilogram of body weight of the human subject ６ or more than about 9.5 x 10 HSPCs per kilogram of body weight of the human subject ６ or more than about 1.0 x 10 HSPCs per kilogram of body weight of the human subject ７ or more than about 1.5 x 10 HSPCs per kilogram of body weight of the human subject ７ or more than about 2.0 x 10 HSPCs per kilogram of body weight of the human subject ７ or more than about 2.5 x 10 HSPCs per kilogram of body weight of the human subject ７ or more than about 3.0 x 10 HSPCs per kilogram of body weight of the human subject ７ or more than about 3.5 x 10 HSPCs per kilogram of body weight of the human subject ７ or more than about 4.0 x 10 HSPCs per kilogram of body weight of the human subject ７ or more than about 4.5 x 10 HSPCs per kilogram of body weight of the human subject ７ or more than about 5.0 x 10 HSPCs per kilogram of body weight of the human subject ７ or more than about 5.5 x 10 HSPCs per kilogram of body weight of the human subject ７ or more than about 6.0 x 10 HSPCs per kilogram of body weight of the human subject ７ or more than about 6.5 x 10 HSPCs per kilogram of body weight of the human subject ７ or more than about 7.0 x 10 HSPCs per kilogram of body weight of the human subject ７ or more than about 7.5 x 10 HSPCs per kilogram of body weight of the human subject ７ or more than about 8.0 x 10 HSPCs per kilogram of body weight of the human subject ７ or more than about 8.5 x 10 HSPCs per kilogram of body weight of the human subject ７ or more than about 9.0 x 10 HSPCs per kilogram of body weight of the human subject ７ or more than about 9.5 x 10 HSPCs per kilogram of body weight of the human subject ７ or more than about 1.0 x 10 HSPCs per kilogram of body weight of the human subject ８ and / or e) the isolated CD45 ＋ The cell population was approximately 5.0 x 10 ５ HSPCs, approximately 6.0 x 10 ５ HSPCs, approximately 7.0 x 10 ５ HSPCs, approximately 8.0 x 10 ５ HSPCs, approximately 9.0 x 10 ５ HSPCs or more, about 1.0 x 10 ６ HSPCs or more, approximately 1.5 x 10 ６ HSPCs, approximately 2.0 x 10 ６ HSPCs, approximately 2.5 x 10 ６ HSPCs, approximately 3.0 x 10 ６ HSPCs, approximately 3.5 x 10 ６ HSPCs, approximately 4.0 x 10 ６ HSPCs, approximately 4.5 x 10 ６ HSPCs, approximately 5.0 x 10 ６ 5.5 x 10 or more HSPCs ６ HSPCs, approximately 6.0 x 10 ６ HSPCs, approximately 6.5 x 10 ６ HSPCs, approximately 7.0 x 10 ６ HSPCs, approximately 7.5 x 10 ６ HSPCs, approximately 8.0 x 10 ６ HSPCs, approximately 8.5 x 10 ６ HSPCs, approximately 9.0 x 10 ６ HSPCs, approximately 9.5 x 10 ６ HSPCs or more, about 1.0 x 10 ７ HSPCs or more, approximately 1.5 x 10 ７ HSPCs, approximately 2.0 x 10 ７ HSPCs, approximately 2.5 x 10 ７ HSPCs, approximately 3.0 x 10 ７ HSPCs, approximately 3.5 x 10 ７ HSPCs, approximately 4.0 x 10 ７ HSPCs, approximately 4.5 x 10 ７ HSPCs, approximately 5.0 x 10 ７ 5.5 x 10 or more HSPCs ７ HSPCs, approximately 6.0 x 10 ７ HSPCs, approximately 6.5 x 10 ７ HSPCs, approximately 7.0 x 10 ７ HSPCs, approximately 7.5 x 10 ７ HSPCs, approximately 8.0 x 10 ７ HSPCs, approximately 8.5 x 10 ７ HSPCs, approximately 9.0 x 10 ７ HSPCs, approximately 9.5 x 10 ７ HSPCs or more, about 1.0 x 10 ８ HSPCs or more, approximately 1.5 x 10 ８ HSPCs, approximately 2.0 x 10 ８ HSPCs, approximately 2.5 x 10 ８ HSPCs, approximately 3.0 x 10 ８ HSPCs, approximately 3.5 x 10 ８ HSPCs, approximately 4.0 x 10 ８ HSPCs, approximately 4.5 x 10 ８ HSPCs, approximately 5.0 x 10 ８ 5.5 x 10 or more HSPCs ８ HSPCs, approximately 6.0 x 10 ８ HSPCs, approximately 6.5 x 10 ８ HSPCs, approximately 7.0 x 10 ８ HSPCs, approximately 7.5 x 10 ８ HSPCs, approximately 8.0 x 10 ８ HSPCs, approximately 8.5 x 10 ８ HSPCs, approximately 9.0 x 10 ８ HSPCs, approximately 9.5 x 10 ８ HSPCs or more, about 1.0 x 10 ９ HSPCs or more, approximately 1.5 x 10 ９ HSPCs, approximately 2.0 x 10 ９ HSPCs, approximately 2.5 x 10 ９ HSPCs, approximately 3.0 x 10 ９ HSPCs, approximately 3.5 x 10 ９ HSPCs, approximately 4.0 x 10 ９ HSPCs, approximately 4.5 x 10 ９ HSPCs, approximately 5.0 x 10 ９ 5.5 x 10 or more HSPCs ９ HSPCs, approximately 6.0 x 10 ９ HSPCs, approximately 6.5 x 10 ９ HSPCs, approximately 7.0 x 10 ９ HSPCs, approximately 7.5 x 10 ９ HSPCs, approximately 8.0 x 10 ９ HSPCs, approximately 8.5 x 10 ９ HSPCs, approximately 9.0 x 10 ９ HSPCs, approximately 9.5 x 10 ９ HSPCs or more, about 1.0 x 10 １０ HSPCs or more, or about 1.5 x 10 １０ and / or f) the isolated CD45 ＋ The cell population was approximately 5.0 x 10 ５ ~Approx. 1.5×10 １０ about 1.0 x 10 Tmem per kilogram of body weight of the human subject receiving the product ５ ~Approx. 1.0×10 ８ and / or g) the isolated CD45 ＋ The population of cells is about 1.0 x 10 per kilogram of body weight of the human subject receiving the product. ５ or more Tmem, about 2.0 x 10 per kilogram of body weight of the human subject receiving the product ５ or more Tmem, about 3.0 x 10 per kilogram of body weight of the human subject receiving the product ５ or more Tmem, about 4.0 x 10 per kilogram of body weight of the human subject receiving the product ５ or more Tmem, about 5.0 x 10 per kilogram of body weight of the human subject receiving the product ５ or more Tmem, about 6.0 x 10 per kilogram of body weight of the human subject receiving the product ５ or more Tmem, about 7.0 x 10 per kilogram of body weight of the human subject receiving the product ５ or more Tmem, about 8.0 x 10 per kilogram of body weight of the human subject receiving the product ５ or more Tmem, about 9.0 x 10 per kilogram of body weight of the human subject receiving the product ５ or more Tmem, about 1.0 x 10 per kilogram of body weight of the human subject receiving the product ６ or more Tmem, about 1.5 x 10 per kilogram of body weight of the human subject receiving the product ６ or more Tmem, about 2.0 x 10 per kilogram of body weight of the human subject receiving the product ６ or more Tmem, about 2.5 x 10 per kilogram of body weight of the human subject receiving the product ６ or more Tmem, about 3.0 x 10 per kilogram of body weight of the human subject receiving the product ６ or more Tmem, about 3.5 x 10 per kilogram of body weight of the human subject receiving the product ６ or more Tmem, about 4.0 x 10 per kilogram of body weight of the human subject receiving the product ６ or more Tmem, about 4.5 x 10 per kilogram of body weight of the human subject receiving the product ６ or more Tmem, about 5.0 x 10 per kilogram of body weight of the human subject receiving the product ６ or more Tmem, about 5.5 x 10 per kilogram of body weight of the human subject receiving the product ６ or more Tmem, about 6.0 x 10 per kilogram of body weight of the human subject receiving the product ６ or more Tmem, about 6.5 x 10 per kilogram of body weight of the human subject receiving the product ６ or more Tmem, about 7.0 x 10 per kilogram of body weight of the human subject receiving the product ６ or more Tmem, about 7.5 x 10 per kilogram of body weight of the human subject receiving the product ６ or more Tmem, about 8.0 x 10 per kilogram of body weight of the human subject receiving the product ６ or more Tmem, about 8.5 x 10 per kilogram of body weight of the human subject receiving the product ６ or more Tmem, about 9.0 x 10 per kilogram of body weight of the human subject receiving the product ６ or more Tmem, about 9.5 x 10 per kilogram of body weight of the human subject receiving the product ６ or more Tmem, about 1.0 x 10 per kilogram of body weight of the human subject receiving the product ７ or more Tmem, about 1.5 x 10 per kilogram of body weight of the human subject receiving the product ７ or more Tmem, about 2.0 x 10 per kilogram of body weight of the human subject receiving the product ７ or more Tmem, about 2.5 x 10 per kilogram of body weight of the human subject receiving the product ７ or more Tmem, about 3.0 x 10 per kilogram of body weight of the human subject receiving the product ７ or more Tmem, about 3.5 x 10 per kilogram of body weight of the human subject receiving the product ７ or more Tmem, about 4.0 x 10 per kilogram of body weight of the human subject receiving the product ７ or more Tmem, about 4.5 x 10 per kilogram of body weight of the human subject receiving the product ７ or more Tmem, about 5.0 x 10 per kilogram of body weight of the human subject receiving the product ７ or more Tmem, about 5.5 x 10 per kilogram of body weight of the human subject receiving the product ７ or more Tmem, about 6.0 x 10 per kilogram of body weight of the human subject receiving the product ７ or more Tmem, about 6.5 x 10 per kilogram of body weight of the human subject receiving the product ７ or more Tmem, about 7.0 x 10 per kilogram of body weight of the human subject receiving the product ７ or more Tmem, about 7.5 x 10 per kilogram of body weight of the human subject receiving the product ７ or more Tmem, about 8.0 x 10 per kilogram of body weight of the human subject receiving the product ７ or more Tmem, about 8.5 x 10 per kilogram of body weight of the human subject receiving the product ７ or more Tmem, about 9.0 x 10 per kilogram of body weight of the human subject receiving the product ７ or more Tmem, about 9.5 x 10 per kilogram of body weight of the human subject receiving the product ７ or more than about 1.0 x 10 Tmem per kilogram of body weight of the human subject receiving the product. ８ and / or h) the isolated CD45 ＋ The cell population was approximately 5.0 x 10 ５ Tmem or more, approximately 6.0 × 10 ５ Tmem or more, approximately 7.0 × 10 ５ More than 8.0 × 10 T ５ More than 10 Tmem, approximately 9.0 × 10 ５ 1.0×10 or more Tmem ６ More than 1.5 × 10 Tmem ６ More than 10 Tmem, approximately 2.0 × 10 ６ More than 10 Tmem, approximately 2.5 × 10 ６ More than 10 Tmem, approximately 3.0 × 10 ６ More than 10 Tmem, approximately 3.5 × 10 ６ Tmem or more, approximately 4.0 × 10 ６ More than 10 Tmem, approximately 4.5 × 10 ６ Tmem or more, approximately 5.0 × 10 ６ More than 5.5×10 Tmem ６ Tmem or more, approximately 6.0 × 10 ６ More than 6.5 × 10 Tmem ６ Tmem or more, approximately 7.0 × 10 ６ More than 7.5 × 10 Tmem ６ More than 8.0 × 10 T ６ More than 8.5 × 10 Tmem ６ More than 10 Tmem, approximately 9.0 × 10 ６ More than 9.5 × 10 Tmem ６ 1.0×10 or more Tmem ７ More than 1.5 × 10 Tmem ７ More than 10 Tmem, approximately 2.0 × 10 ７ More than 10 Tmem, approximately 2.5 × 10 ７ More than 10 Tmem, approximately 3.0 × 10 ７ More than 10 Tmem, approximately 3.5 × 10 ７ Tmem or more, approximately 4.0 × 10 ７ More than 10 Tmem, approximately 4.5 × 10 ７ Tmem or more, approximately 5.0 × 10 ７ More than 5.5×10 Tmem ７ Tmem or more, approximately 6.0 × 10 ７ More than 6.5 × 10 Tmem ７ Tmem or more, approximately 7.0 × 10 ７ More than 7.5 × 10 Tmem ７ More than 8.0 × 10 T ７ More than 8.5 × 10 Tmem ７ More than 10 Tmem, approximately 9.0 × 10 ７ More than 9.5 × 10 Tmem ７ 1.0×10 or more Tmem ８ More than 1.5 × 10 Tmem ８ More than 10 Tmem, approximately 2.0 × 10 ８ More than 10 Tmem, approximately 2.5 × 10 ８ More than 10 Tmem, approximately 3.0 × 10 ８ More than 10 Tmem, approximately 3.5 × 10 ８ Tmem or more, approximately 4.0 × 10 ８ More than 10 Tmem, approximately 4.5 × 10 ８ Tmem or more, approximately 5.0 × 10 ８ More than 5.5×10 Tmem ８ Tmem or more, approximately 6.0 × 10 ８ More than 6.5 × 10 Tmem ８ Tmem or more, approximately 7.0 × 10 ８ More than 7.5 × 10 Tmem ８ More than 8.0 × 10 T ８ More than 8.5 × 10 Tmem ８ More than 10 Tmem, approximately 9.0 × 10 ８ More than 9.5 × 10 Tmem ８ 1.0×10 or more Tmem ９ More than 1.5 × 10 Tmem ９ More than 10 Tmem, approximately 2.0 × 10 ９ More than 10 Tmem, approximately 2.5 × 10 ９ More than 10 Tmem, approximately 3.0 × 10 ９ More than 10 Tmem, approximately 3.5 × 10 ９ Tmem or more, approximately 4.0 × 10 ９ More than 10 Tmem, approximately 4.5 × 10 ９ Tmem or more, approximately 5.0 × 10 ９ More than 5.5×10 Tmem ９ Tmem or more, approximately 6.0 × 10 ９ More than 6.5 × 10 Tmem ９ Tmem or more, approximately 7.0 × 10 ９ More than 7.5 × 10 Tmem ９ More than 8.0 × 10 T ９ More than 8.5 × 10 Tmem ９ More than 10 Tmem, approximately 9.0 × 10 ９ More than 9.5 × 10 Tmem ９ 1.0×10 or more Tmem １０ 10 or more Tmem, or about 1.5 x 10 １０ and / or i) the isolated CD45 ＋ the population of cells is about 1.0 x 10 per kilogram of body weight of said human subject ５ ~Approx. 2.0×10 ７ fresh Tregs, or approximately 5.0 x 10 ５ ~Approx. 3.0×10 ９ fresh Tregs; and / or j) the isolated CD45 ＋ the population of cells is about 1.0 x 10 per kilogram of body weight of said human subject ５ or more fresh Tregs, about 2.0 x 10 per kilogram of body weight of the human subject ５ or more fresh Tregs, about 3.0 x 10 per kilogram of body weight of the human subject ５ or more fresh Tregs, about 4.0 x 10 per kilogram of body weight of the human subject ５ or more fresh Tregs, about 5.0 x 10 per kilogram of body weight of the human subject ５ or more fresh Tregs, about 6.0 x 10 per kilogram of body weight of the human subject ５ or more fresh Tregs, about 7.0 x 10 per kilogram of body weight of the human subject ５ or more fresh Tregs, about 8.0 x 10 per kilogram of body weight of the human subject ５ or more fresh Tregs, about 9.0 x 10 per kilogram of body weight of the human subject ５ or more fresh Tregs, about 1.0 x 10 per kilogram of body weight of the human subject ６ or more fresh Tregs, about 1.5 x 10 per kilogram of body weight of the human subject ６ or more fresh Tregs, about 2.0 x 10 per kilogram of body weight of the human subject ６ or more fresh Tregs, about 2.5 x 10 per kilogram of body weight of the human subject ６ or more fresh Tregs, about 3.0 x 10 per kilogram of body weight of the human subject ６ or more fresh Tregs, about 3.5 x 10 per kilogram of body weight of the human subject ６ or more fresh Tregs, about 4.0 x 10 per kilogram of body weight of the human subject ６ or more fresh Tregs, about 4.5 x 10 per kilogram of body weight of the human subject ６ or more fresh Tregs, about 5.0 x 10 per kilogram of body weight of the human subject ６ or more fresh Tregs, about 5.5 x 10 per kilogram of body weight of the human subject ６ or more fresh Tregs, about 6.0 x 10 per kilogram of body weight of the human subject ６ or more fresh Tregs, about 6.5 x 10 per kilogram of body weight of the human subject ６ or more fresh Tregs, about 7.0 x 10 per kilogram of body weight of the human subject ６ or more fresh Tregs, about 7.5 x 10 per kilogram of body weight of the human subject ６ or more fresh Tregs, about 8.0 x 10 per kilogram of body weight of the human subject ６ or more fresh Tregs, about 8.5 x 10 per kilogram of body weight of the human subject ６ or more fresh Tregs, about 9.0 x 10 per kilogram of body weight of the human subject ６ or more fresh Tregs, about 9.5 x 10 per kilogram of body weight of the human subject ６ or more fresh Tregs, about 1.0 x 10 per kilogram of body weight of the human subject ７ or more fresh Tregs, about 1.5 x 10 per kilogram of body weight of the human subject ７ or more than about 2.0 x 10 fresh Tregs per kilogram of body weight of the human subject ７ and / or k) the isolated CD45 ＋ The cell population was approximately 5.0 x 10 ５ fresh Tregs, approximately 6.0 x 10 ５ fresh Tregs, approximately 7.0 x 10 ５ fresh Tregs, approximately 8.0 x 10 ５ fresh Tregs, approximately 9.0 x 10 ５ fresh Tregs, approximately 1.0 x 10 ６ fresh Tregs, approximately 1.5 x 10 ６ fresh Tregs, approximately 2.0 x 10 ６ fresh Tregs, approximately 2.5 x 10 ６ fresh Tregs, approximately 3.0 x 10 ６ fresh Tregs, approximately 3.5 x 10 ６ fresh Tregs, approximately 4.0 x 10 ６ fresh Tregs, approximately 4.5 x 10 ６ fresh Tregs, approximately 5.0 x 10 ６ fresh Tregs, approximately 5.5 x 10 ６ fresh Tregs, approximately 6.0 x 10 ６ fresh Tregs, approximately 6.5 x 10 ６ fresh Tregs, approximately 7.0 x 10 ６ fresh Tregs, approximately 7.5 x 10 ６ fresh Tregs, approximately 8.0 x 10 ６ fresh Tregs, approximately 8.5 x 10 ６ fresh Tregs, approximately 9.0 x 10 ６ fresh Tregs, approximately 9.5 x 10 ６ fresh Tregs, approximately 1.0 x 10 ７ fresh Tregs, approximately 1.5 x 10 ７ fresh Tregs, approximately 2.0 x 10 ７ fresh Tregs, approximately 2.5 x 10 ７ fresh Tregs, approximately 3.0 x 10 ７ fresh Tregs, approximately 3.5 x 10 ７ fresh Tregs, approximately 4.0 x 10 ７ fresh Tregs, approximately 4.5 x 10 ７ fresh Tregs, approximately 5.0 x 10 ７ fresh Tregs, approximately 5.5 x 10 ７ fresh Tregs, approximately 6.0 x 10 ７ fresh Tregs, approximately 6.5 x 10 ７ fresh Tregs, approximately 7.0 x 10 ７ fresh Tregs, approximately 7.5 x 10 ７ fresh Tregs, approximately 8.0 x 10 ７ fresh Tregs, approximately 8.5 x 10 ７ fresh Tregs, approximately 9.0 x 10 ７ fresh Tregs, approximately 9.5 x 10 ７ fresh Tregs, approximately 1.0 x 10 ８ fresh Tregs, approximately 1.5 x 10 ８ fresh Tregs, approximately 2.0 x 10 ８ fresh Tregs, approximately 2.5 x 10 ８ fresh Tregs, approximately 3.0 x 10 ８ fresh Tregs, approximately 3.5 x 10 ８ fresh Tregs, approximately 4.0 x 10 ８ fresh Tregs, approximately 4.5 x 10 ８ fresh Tregs, approximately 5.0 x 10 ８ fresh Tregs, approximately 5.5 x 10 ８ fresh Tregs, approximately 6.0 x 10 ８ fresh Tregs, approximately 6.5 x 10 ８ fresh Tregs, approximately 7.0 x 10 ８ fresh Tregs, approximately 7.5 x 10 ８ fresh Tregs, approximately 8.0 x 10 ８ fresh Tregs, approximately 8.5 x 10 ８ fresh Tregs, approximately 9.0 x 10 ８ fresh Tregs, approximately 9.5 x 10 ８ fresh Tregs, approximately 1.0 x 10 ９ fresh Tregs, approximately 1.5 x 10 ９ fresh Tregs, approximately 2.0 x 10 ９ fresh Tregs, approximately 2.5 x 10 ９ fresh Tregs or approximately 3.0 x 10 ９ and / or l) the isolated CD45 ＋ The population of cells is about 5.0 x 10 per kilogram of body weight of the human subject receiving the product. ５ less than about 4.5 x 10 per kilogram of body weight of the human subject receiving the product ５ less than about 4.0 x 10 per kilogram of body weight of the human subject receiving the product ５ less than about 3.5 x 10 per kilogram of body weight of the human subject receiving the product ５ less than about 3.0 x 10 T per kilogram of body weight of the human subject receiving the product ５ less than about 2.5 x 10 per kilogram of body weight of the human subject receiving the product ５ less than about 2.0 x 10 per kilogram of body weight of the human subject receiving the product ５ less than about 1.5 x 10 per kilogram of body weight of the human subject receiving the product ５ less than about 1.0 x 10 per kilogram of body weight of the human subject receiving the product ５ less than about 9.5 x 10 T per kilogram of body weight of the human subject receiving the product ４ less than about 9.0 x 10 T per kilogram of body weight of the human subject receiving the product ４ less than about 8.5 x 10 per kilogram of body weight of the human subject receiving the product ４ less than about 8.0 x 10 T per kilogram of body weight of the human subject receiving the product ４ less than about 7.5 x 10 per kilogram of body weight of the human subject receiving the product ４ less than about 7.0 x 10 T per kilogram of body weight of the human subject receiving the product ４ less than about 6.5 x 10 per kilogram of body weight of the human subject receiving the product ４ less than about 6.0 x 10 per kilogram of body weight of the human subject receiving the product ４ less than about 5.5 x 10 per kilogram of body weight of the human subject receiving the product ４ less than about 5.0 x 10 T per kilogram of body weight of the human subject receiving the product ４ less than about 4.5 x 10 per kilogram of body weight of the human subject receiving the product ４ less than about 4.0 x 10 per kilogram of body weight of the human subject receiving the product ４ less than about 3.5 x 10 per kilogram of body weight of the human subject receiving the product ４ less than about 3.0 x 10 T per kilogram of body weight of the human subject receiving the product ４ less than about 2.5 x 10 per kilogram of body weight of the human subject receiving the product ４ less than about 2.0 x 10 per kilogram of body weight of the human subject receiving the product ４ less than about 1.5 x 10 per kilogram of body weight of the human subject receiving the product ４ less than about 1.0 x 10 per kilogram of body weight of the human subject receiving the product ４ less than about 9.5 x 10 T per kilogram of body weight of the human subject receiving the product ３ less than about 9.0 x 10 T per kilogram of body weight of the human subject receiving the product ３ less than about 8.5 x 10 per kilogram of body weight of the human subject receiving the product ３ less than about 8.0 x 10 T per kilogram of body weight of the human subject receiving the product ３ less than about 7.5 x 10 per kilogram of body weight of the human subject receiving the product ３ less than about 7.0 x 10 T per kilogram of body weight of the human subject receiving the product ３ less than about 6.5 x 10 per kilogram of body weight of the human subject receiving the product ３ less than about 6.0 x 10 per kilogram of body weight of the human subject receiving the product ３ less than about 5.5 x 10 per kilogram of body weight of the human subject receiving the product ３ less than about 5.0 x 10 T per kilogram of body weight of the human subject receiving the product ３ less than about 4.5 x 10 per kilogram of body weight of the human subject receiving the product ３ less than about 4.0 x 10 per kilogram of body weight of the human subject receiving the product ３ less than about 3.5 x 10 per kilogram of body weight of the human subject receiving the product ３ less than about 3.0 x 10 T per kilogram of body weight of the human subject receiving the product ３ less than about 2.5 x 10 per kilogram of body weight of the human subject receiving the product ３ less than about 2.0 x 10 per kilogram of body weight of the human subject receiving the product ３ less than about 1.5 x 10 per kilogram of body weight of the human subject receiving the product ３ or less than about 1.0 x 10 per kilogram of body weight of the human subject receiving the product. ３ contains fewer than Tcon; and / or m) the isolated CD45 ＋ The cell population was approximately 6.0 x 10 ７ Tcon less than about 5.5×10 ７ Tcon less than about 5.0 x 10 ７ Tcon less than about 4.5×10 ７ Tcon less than about 4.0 x 10 ７ Tcon less than about 3.5×10 ７ Tcon less than about 3.0 x 10 ７ Tcon less than about 2.5×10 ７ Tcon less than about 2.0 x 10 ７ Tcon less than about 1.5×10 ７ Tcon less than about 1.0 x 10 ７ Tcon less than about 9.5×10 ６ Tcon less than about 9.0 x 10 ６ Tcon less than about 8.5×10 ６ Tcon less than about 8.0 x 10 ６ Tcon less than about 7.5×10 ６ Tcon less than about 7.0 x 10 ６ Tcon less than about 6.5×10 ６ Tcon less than about 6.0 x 10 ６ Tcon less than about 5.5×10 ６ Tcon less than about 5.0 x 10 ６ Tcon less than about 4.5×10 ６ Tcon less than about 4.0 x 10 ６ Tcon less than about 3.5×10 ６ Tcon less than about 3.0 x 10 ６ Tcon less than about 2.5×10 ６ Tcon less than about 2.0 x 10 ６ Tcon less than about 1.5×10 ６ Less than Tcon, or about 1.0 x 10 ６ contains fewer than Tcon; and / or n) the isolated CD45 ＋ A population of cells expressing TCR Vα24Jα18 ＋ CD127 ＋ and optionally, said isolated CD45 ＋ The population of cells is about 5.0 x 10 per kilogram of body weight of the human subject receiving the product. ２ ~Approx. 2.0×10 ６ iNKTs, or approximately 2.0 x 10 ３ ~Approx. 4.0×10 ８ iNKTs, and optionally, said isolated CD45 ＋ The population of cells is about 5.0 x 10 per kilogram of body weight of the human subject receiving the product. ２ or more iNKTs, about 6.0 x 10 per kilogram of body weight of said human subject receiving said product ２ or more iNKTs, about 7.0 x 10 per kilogram of body weight of said human subject receiving said product ２ or more iNKTs, about 8.0 x 10 per kilogram of body weight of said human subject receiving said product ２ or more iNKTs, about 9.0 x 10 per kilogram of body weight of said human subject receiving said product ２ or more iNKTs, about 1.0 x 10 per kilogram of body weight of said human subject receiving said product ３ or more iNKTs, about 2.0 x 10 per kilogram of body weight of said human subject receiving said product ３ or more iNKTs, about 3.0 x 10 per kilogram of body weight of said human subject receiving said product ３ or more iNKTs, about 4.0 x 10 per kilogram of body weight of said human subject receiving said product ３ or more iNKTs, about 5.0 x 10 per kilogram of body weight of said human subject receiving said product ３ or more iNKTs, about 6.0 x 10 per kilogram of body weight of said human subject receiving said product ３ or more iNKTs, about 7.0 x 10 per kilogram of body weight of said human subject receiving said product ３ or more iNKTs, about 8.0 x 10 per kilogram of body weight of said human subject receiving said product ３ or more iNKTs, about 9.0 x 10 per kilogram of body weight of said human subject receiving said product ３ or more iNKTs, about 1.0 x 10 per kilogram of body weight of said human subject receiving said product ４ or more iNKTs, about 2.0 x 10 per kilogram of body weight of said human subject receiving said product ４ or more iNKTs, about 3.0 x 10 per kilogram of body weight of said human subject receiving said product ４ or more iNKTs, about 4.0 x 10 per kilogram of body weight of said human subject receiving said product ４ or more iNKTs, about 5.0 x 10 per kilogram of body weight of said human subject receiving said product ４ or more iNKTs, about 6.0 x 10 per kilogram of body weight of said human subject receiving said product ４ or more iNKTs, about 7.0 x 10 per kilogram of body weight of said human subject receiving said product ４ or more iNKTs, about 8.0 x 10 per kilogram of body weight of said human subject receiving said product ４ or more iNKTs, about 9.0 x 10 per kilogram of body weight of said human subject receiving said product ４ or more iNKTs, about 1.0 x 10 per kilogram of body weight of said human subject receiving said product ５ or more iNKTs, about 2.0 x 10 per kilogram of body weight of said human subject receiving said product ５ or more iNKTs, about 3.0 x 10 per kilogram of body weight of said human subject receiving said product ５ or more iNKTs, about 4.0 x 10 per kilogram of body weight of said human subject receiving said product ５ or more iNKTs, about 5.0 x 10 per kilogram of body weight of said human subject receiving said product ５ or more iNKTs, about 6.0 x 10 per kilogram of body weight of said human subject receiving said product ５ or more iNKTs, about 7.0 x 10 per kilogram of body weight of said human subject receiving said product ５ or more iNKTs, about 8.0 x 10 per kilogram of body weight of said human subject receiving said product ５ or more iNKTs, about 9.0 x 10 per kilogram of body weight of said human subject receiving said product ５ or more iNKTs, about 1.0 x 10 per kilogram of body weight of said human subject receiving said product ６ or more iNKTs, about 1.5 x 10 per kilogram of body weight of said human subject receiving said product ６ or more than about 2.0 x 10 iNKTs per kilogram of body weight of said human subject receiving said product. ６ and optionally, said isolated CD45 ＋ The cell population was approximately 2.0 x 10 ３ More than 3.0 x 10 iNKTs ３ More than 4.0 x 10 iNKTs ３ More than 5.0 x 10 iNKTs ３ More than 6.0 x 10 iNKTs ３ More than 7.0 x 10 iNKTs ３ More than 8.0 x 10 iNKTs ３ More than 9.0 x 10 iNKTs ３ More than 1.0 x 10 iNKTs ４ More than 2.0 x 10 iNKTs ４ More than 3.0 x 10 iNKTs ４ More than 4.0 x 10 iNKTs ４ More than 5.0 x 10 iNKTs ４ More than 6.0 x 10 iNKTs ４ More than 7.0 x 10 iNKTs ４ More than 8.0 x 10 iNKTs ４ More than 9.0 x 10 iNKTs ４ More than 1.0 x 10 iNKTs ５ More than 2.0 x 10 iNKTs ５ More than 3.0 x 10 iNKTs ５ More than 4.0 x 10 iNKTs ５ More than 5.0 x 10 iNKTs ５ More than 6.0 x 10 iNKTs ５ More than 7.0 x 10 iNKTs ５ More than 8.0 x 10 iNKTs ５ More than 9.0 x 10 iNKTs ５ More than 1.0 x 10 iNKTs ６ More than 1.5 x 10 iNKTs ６ More than 2.0 x 10 iNKTs ６ More than 2.5 x 10 iNKTs ６ More than 3.0 x 10 iNKTs ６ More than 3.5 x 10 iNKTs ６ More than 4.0 x 10 iNKTs ６ More than 4.5 x 10 iNKTs ６ More than 5.0 x 10 iNKTs ６ More than 5.5 x 10 iNKTs ６ More than 6.0 x 10 iNKTs ６ More than 6.5 x 10 iNKTs ６ More than 7.0 x 10 iNKTs ６ More than 7.5 x 10 iNKTs ６ More than 8.0 x 10 iNKTs ６ More than 8.5 x 10 iNKTs ６ More than 9.0 x 10 iNKTs ６ More than 9.5 x 10 iNKTs ６ More than 1.0 x 10 iNKTs ７ More than 1.5 x 10 iNKTs ７ More than 2.0 x 10 iNKTs ７ More than 2.5 x 10 iNKTs ７ More than 3.0 x 10 iNKTs ７ More than 3.5 x 10 iNKTs ７ More than 4.0 x 10 iNKTs ７ More than 4.5 x 10 iNKTs ７ More than 5.0 x 10 iNKTs ７ More than 5.5 x 10 iNKTs ７ More than 6.0 x 10 iNKTs ７ More than 6.5 x 10 iNKTs ７ More than 7.0 x 10 iNKTs ７ More than 7.5 x 10 iNKTs ７ More than 8.0 x 10 iNKTs ７ More than 8.5 x 10 iNKTs ７ More than 9.0 x 10 iNKTs ７ More than 9.5 x 10 iNKTs ７ More than 1.0 x 10 iNKTs ８ More than 1.5 x 10 iNKTs ８ More than 2.0 x 10 iNKTs ８ More than 2.5 x 10 iNKTs ８ More than 3.0 x 10 iNKTs ８ More than 3.5 x 10 iNKTs ８ or more iNKTs, or approximately 4.0 x 10 ８ or more iNKTs, optionally wherein said iNKTs are CD1d-tet ＋ , 6B11 ＋ , or CD1d-tet ＋ 6B11 ＋ and / or o) the isolated CD45 ＋ the population of cells is derived from an allogeneic donor with at least one HLA mismatch compared to said human subject; and / or p) the HSPC is cKIT ＋ , CD133 ＋ , CD90 ＋ , CD38 － , CD45RA － , Lin － , CD19 － , TCRα － or any combination thereof, and / or q) the Tmem is CD3 ＋ CD45RO ＋ and / or r) the Tmem is a T central memory cell (T ＣＭ ), a population of T effector memory cells (T ＥＭ ) population, T stem center memory cells (T ＳＣＭ ), or any combination thereof, and optionally, ＣＭ is CD4 ＋ CD45RO ＋ or CD8 ＋ CD45RO ＋ and / or the T ＣＭ is CD45RA － , CD62L ＋ , CCR7 ＋ or any combination thereof, and optionally, ＥＭ is CD4 ＋ , CD45RO ＋ , CD45RA － , CD62L － , CCR7 － or any combination thereof, and optionally, ＳＣＭ is CD4 ＋ CD45RA ＋ or CD8 ＋ CD45RA ＋ and / or the T ＳＣＭ is CD95 ＋ , CD122 ＋ , CXCR3 ＋ , LFA-1 ＋ or any combination thereof, and / or s) the Treg is FOXP3 ＋ and / or t) said Tregs comprise a population of naive Treg cells, a population of memory Treg cells, or a population of naive and memory Treg cells, and optionally said naive Treg cells are CD4 ＋ CD25 ＋ CD127 ｄｉｍ FoxP3 ＋ CD45RA ＋ CD45RO － and optionally the Tregs are about 2.0 x 10 per kilogram of body weight of the human subject receiving the product. ５ pieces ~ approx. 5.0 x 10 ８ naive Treg cells, or approximately 8.0 x 10 ５ pieces ~ approx. 1.0×10 １１ naive Treg cells, and optionally, said memory Treg cells are CD4 ＋ CD25 ＋ CD127 ｄｉｍ FoxP3 ＋ CD45RA － CD45RO ＋ and optionally the Tregs are about 5.0 x 10 per kilogram of body weight of the human subject receiving the product. ４ pieces ~ approx. 5.0 x 10 ８ memory Treg cells, or approximately 2.0 x 10 ５ pieces ~ approx. 1.0×10 １１ memory Treg cells; and / or u) the Tcon is TCRα ＋ , TCRβ ＋ , or TCRα ＋ TCRβ ＋ and / or said Tcon is CD25 － , CD127 ＋ , or CD25 － CD127 ＋ and / or said Tcon is TCRα ＋ TCRβ ＋ CD45RA ＋ CD45RO － CD25 － CD95 － IL-2Rβ － CD127 ＋ and / or v) the isolated CD45 ＋ the population of cells contains less than about 5 EU to less than about 0.5 EU endotoxin per mL of formulation; and / or w) the HSPCs, the Tmems, the Tregs, or any combination thereof are obtained from an allogeneic donor that is HLA-matched relative to the human subject receiving the product, or the isolated CD45 ＋ the population of cells is derived from an allogeneic donor that is HLA-matched relative to the human subject receiving the product; and / or x) the HSPCs, the Tmems, the Tregs, or any combination thereof are obtained from an allogeneic donor having at least one HLA mismatch compared to the human subject receiving the product, or the isolated CD45 ＋ The population of cells is derived from an allogeneic donor having at least one HLA mismatch relative to the human subject receiving the product, and optionally the at least one HLA mismatch is at an allele selected from the group consisting of HLA-A, HLA-B, HLA-C, HLA-DRB1, and any combination thereof, and optionally the cells with at least one HLA mismatch are derived from a donor that is 6 / 8 HLA mismatched relative to the human subject receiving the product, or 7 / 8 HLA mismatched relative to the human subject receiving the product. The cells are derived from a donor that is 7 / 8 HLA-mismatched relative to the human subject receiving the product, and optionally the cells having at least one HLA mismatch are derived from a donor that is 7 / 8 HLA-mismatched relative to the human subject receiving the product, and optionally the donor that is 7 / 8 HLA-mismatched relative to the human subject receiving the product has a mismatch in HLA-A, and optionally the donor that is 7 / 8 HLA-mismatched relative to the human subject receiving the product has a mismatch in HLA-B, and optionally the donor that is 7 / 8 HLA-mismatched relative to the human subject receiving the product. the donor has a mismatch at HLA-C, and optionally is a 7 / 8 HLA mismatch compared to the human subject receiving the product; the donor has a mismatch at HLA-DRB1, and optionally is a 7 / 8 HLA mismatch compared to the human subject receiving the product; the donor has a mismatch at HLA-DRB1, and optionally is a 7 / 8 HLA mismatch compared to the human subject receiving the product; the donor has a mismatched HLA allele because the donor is homozygous for the HLA allele but the human subject receiving the product is heterozygous for the HLA allele; and optionally is a 7 / 8 HLA mismatch compared to the human subject receiving the product; the donor has at least one HLA mismatch compared to the human subject receiving the product because the donor is heterozygous for the HLA allele, but the human subject receiving the product is homozygous for the HLA allele; optionally, the donor has at least one HLA mismatch compared to the human subject receiving the product because both the donor and the human subject receiving the product are heterozygous for the HLA allele; and / or y) the HSPCs, the Tmems, the Tregs, or any combination thereof are obtained from a half-matched allogeneic donor compared to the human subject receiving the product, or the isolated CD45 ＋ the population of cells is derived from a half-matched allogeneic donor relative to the human subject receiving the product; and / or z) the allogeneic donor is related to the human subject receiving the product, or the allogeneic donor is unrelated to the human subject receiving the product; and / or aa) an overall survival rate of at least 12 months after administration of the cell therapy product ranging from about 75% to about 100%; and / or bb) the overall survival of the human subject is increased after administration of the cell therapy product compared to a corresponding human subject receiving standard myeloablative allogeneic hematopoietic stem cell transplant (alloHSCT); and / or cc) a GVHD- and relapse-free survival (GFRS) rate of at least 12 months after administration of the cell therapy product is in the range of about 65% to about 100%; and / or dd) the human subject's GVHD- and relapse-free survival (GFRS) is increased after administration of the cell therapy product compared to a corresponding human subject receiving standard myeloablative allogeneic hematopoietic stem cell transplant (alloHSCT); and / or ee) recurrence-free survival at least 12 months after administration of the cell therapy product is in the range of about 70% to about 100%; and / or ff) relapse-free survival of said human subject is increased after administration of said cell therapy product compared to a corresponding human subject receiving standard myeloablative allogeneic hematopoietic stem cell transplant (alloHSCT); and / or gg) the incidence of acute GVHD for 100 days or more after administration of the cell therapy product ranges from about 9% to about 31%; and / or hh) the incidence of chronic GVHD for 100 days or more after administration of the cell therapy product ranges from about 1% to about 10%; and / or ii) the incidence of post-transplant lymphoproliferative disorder (PTLD) for 100 days or more after administration of the cell therapy product ranges from about 1% to about 10%; and / or jj) the incidence of Grade 2 or higher infections during the 100 days or more following administration of the cell therapy product ranges from about 23% to about 31%. The method of claim 7.

9. The method further comprises administering a conditioning regimen prior to administration of the cell therapy product, optionally wherein the conditioning regimen is administered from about two days to about ten days prior to administration of the multicomponent cell therapy, and optionally wherein the conditioning regimen is a total body irradiation-based (TBI-based) regimen or a total lymphatic irradiation-based (TLI-based) regimen, and optionally wherein the TBI-based regimen comprises fractionated total body irradiation, and optionally wherein the fractionated total body irradiation is administered in two or more, three or more, four or more, five or more, six or more, seven or more, eight ... and optionally, the fractionated total body irradiation comprises a total dose in the range of about 500 to about 1600 cGy; and optionally, the TBI-based regimen further comprises one or more transplant conditioning reagents, and optionally, the one or more transplant conditioning reagents are selected from the group consisting of cyclophosphamide, etoposide, fludarabine, thiotepa, antithymocyte globulin (ATG), and any combination thereof. and optionally, the myeloablative conditioning regimen is a myeloablative conditioning regimen, optionally comprising one or more conditioning reagents, optionally wherein the one or more conditioning reagents are selected from the group consisting of thiotepa, busulfan, melphalan, fludarabine, cyclophosphamide, antithymocyte globulin (ATG), and any combination thereof; and optionally, the myeloablative conditioning regimen comprises three or more conditioning reagents, at least one of which is selected from the group consisting of thiotepa, busulfan, melphalan, fludarabine, cyclophosphamide, antithymocyte globulin (ATG), and any combination thereof.

9. The method of claim 7 or claim 8, wherein the myeloablative conditioning regimen comprises otepa, and optionally comprises one or more doses of busulfan, fludarabine, and thiotepa, wherein the one or more doses of busulfan, fludarabine, and thiotepa comprise about 5 to about 12 mg of thiotepa per kilogram of body weight of the human subject, about 7 to about 11 mg of busulfan per kilogram of body weight of the human subject, and about 100 to about 200 mg of fludarabine per square meter of body surface area, respectively.

10. The method further comprises collecting one or more mobilized peripheral blood donations from the donor, optionally the peripheral blood donations have been mobilized with granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), plerixafor, or any combination thereof; optionally, at least one of the mobilized peripheral blood donations is processed and sorted using one or more immunoseparation particles (ISPs) to enrich for HSPCs, Tmems, and Tregs; optionally, the one or more ISPs comprise affinity reagents; optionally, the affinity reagents are immunomagnetic separation particles; optionally, the immunomagnetic separation particles are antibodies each bound to an iron-containing particle; optionally, the affinity reagents comprise a plurality of CD34 reagents that bind to CD34 on HSPCs; and optionally, the isolated CD45 ＋ the average number of ISPs per HSPC in the population of cells is about 20,000 or less, and optionally, said isolated CD45 ＋ The average number of ISPs per HSPC in the population of cells is about 1,000 to about 20,000; optionally, the affinity reagent comprises a plurality of CD45RA reagents that bind to one or more CD45RA receptors on Tmems; optionally, the affinity reagent comprises a plurality of CD25 reagents that bind to one or more CD25 receptors on Tregs; and optionally, the isolated CD45 ＋ the average number of ISPs per Treg in the population of cells is about 4000 or less, and optionally, said isolated CD45 ＋ The method of any one of claims 7 to 9, wherein the average number of ISPs per Treg in the population of cells is about 1500 to about 2500.

11. a) the human subject is about 3 months of age or older, and / or b) the human subject is between about 3 months and about 18 years of age; and / or c) the human subject is about 12 years of age or older; and / or d) the human subject is between about 12 and about 65 years of age; and / or e) the human subject is between about 18 and about 65 years of age; and / or f) the human subject is between about 12 and about 75 years of age; and / or g) the human subject is between about 65 and about 75 years of age; and / or h) the human subject is between about 3 months and about 75 years of age; and / or i) the human subject has received one to five prior lines of therapy; The method according to any one of claims 7 to 10.

12. 10. A cell therapy kit comprising the cell therapy product of any one of claims 1-6, optionally further comprising written instructions for using the cell therapy to treat a malignant hematological disease in a human subject, optionally wherein the malignant hematological disease is selected from the group consisting of leukemia, acute leukemia, acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), mixed phenotype acute leukemia (MPAL), chronic myelogenous leukemia (CML), multiple myeloma, lymphoma, Hodgkin's lymphoma, non-Hodgkin's lymphoma, myelodysplastic syndrome (MDS), myeloproliferative syndrome, myelofibrosis, and blastic plasmacytoid dendritic cell neoplasm (BPDCN).

13. Optionally, said isolated CD45 ＋ 7. A unit dose comprising the cell therapy product of any one of claims 1 to 6, wherein the population of cells further comprises one or more excipients.

14. 10. An article of manufacture comprising the cell therapy product of any one of claims 1-6, optionally further comprising instructions for administering the article of manufacture to a human subject to be treated for a hematological malignancy, optionally wherein the hematological malignancy is selected from the group consisting of leukemia, acute leukemia, acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), mixed phenotype acute leukemia (MPAL), chronic myelogenous leukemia (CML), multiple myeloma, lymphoma, Hodgkin's lymphoma, non-Hodgkin's lymphoma, myelodysplastic syndrome (MDS), myeloproliferative syndrome, myelofibrosis, and blastic plasmacytoid dendritic cell neoplasm (BPDCN).

15. A container comprising the cell therapy product of any one of claims 1 to 6.

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