Compositions and methods for hematopoietic stem cell transplantation

Abstract

The present disclosure provides different therapeutic cell populations that form pharmaceutical compositions useful for hematopoietic stem / progenitor cell transplantation. For example, the present disclosure provides a therapeutic cell population comprising an enriched population of hematopoietic stem / progenitor cells, memory T cells, regulatory T cells, and wherein the cell population depletes the primary conventional alpha beta-T cells. The present disclosure further provides methods of treatment using the therapeutic cell population. In other embodiments, the present disclosure provides methods of generating a population of therapeutic cells.

Description

[0001] Cross - reference to related applications

[0002] This application claims the benefit of the priority of U.S. Provisional Application No. 63 / 422,375, filed on November 3, 2022, and U.S. Provisional Application No. 63 / 520,234, filed on August 17, 2023, each of which is incorporated herein by reference in its entirety for all purposes. Background of the Invention

[0003] Myeloablative (MA) allogeneic hematopoietic cell transplantation (alloHCT) is the standard treatment for various hematological malignancies. However, MA - alloHCT is curative only in some patients, and better strategies for alloHCT remain a critical need to improve patient outcomes. Summary of the Invention

[0004] One aspect of the present disclosure is a pharmaceutical composition comprising one or more unit doses of a cell graft, wherein each unit dose of the cell graft comprises a therapeutic cell population per kilogram (kg) of the body weight of a subject receiving the cell graft. Each unit dose of the therapeutic cell population comprises: more than 3×10 5 hematopoietic stem / progenitor cells (HSPCs) per kilogram of the body weight of the subject receiving the cell graft, more than 3×10 5 memory T cells (Tmem) per kilogram of the body weight of the subject receiving the cell graft, more than 5×10 5 regulatory T cells (Tregs) per kilogram of the body weight of the subject receiving the cell graft, and less than 3×10 5 naive conventional αβ - T cells per kilogram of the body weight of the subject receiving the cell graft. In this regard, the subject receiving the cell graft has received a myeloablative conditioning regimen comprising thiotepa, and / or the subject receiving the cell graft is receiving or will receive a GVHD prophylaxis regimen comprising tacrolimus.

[0005] In an embodiment, the unit dose further comprises from 0.5×10 3 to 2000×10 3 invariant natural killer T (iNKT) cells per kilogram of the body weight of the subject receiving the cell graft.

[0006] In various embodiments, the HSPC is CD34+, the Tmem is CD3+CD45RA-CD45RO+, the Treg is CD4+CD25+CD127- / lo, CD45RA+ or a combination thereof, and the naive conventional αβ-T cell is CD3+CD45RA+CD25-TCR Va24Ja18-.

[0007] In some embodiments, the iNKT is CD3+Vα24Jα18+.

[0008] In embodiments, each unit dose of the therapeutic cell population comprises: 1.0×10 6 to 50×10 6 HSPCs per kg of body weight of the subject receiving the cell graft, 0.3×10 6 to 1000×10 6 Tmem per kg of body weight of the subject receiving the cell graft, 0.5×10 6 to 1000×10 6 Tregs and less than 3×10 5 naive conventional αβ-T cells per kg of body weight of the subject receiving the cell graft.

[0009] In various embodiments, the unit dose further comprises iNKT cells, wherein each unit dose of the therapeutic cell population comprises: 1.0×10 6 to 50×10 6 HSPCs per kg of body weight of the subject receiving the cell graft, 0.3×10 6 to 1000×10 6 Tmem per kg of body weight of the subject receiving the cell graft, 0.5×10 6 to 1000×10 6 Tregs, 0.5×10 3 to 2000×10 3 iNKTs per kg of body weight of the subject receiving the cell graft and less than 3×10 5 naive conventional αβ-T cells per kg of body weight of the subject receiving the cell graft.

[0010] In some embodiments, each unit dose of the therapeutic cell population comprises 0.2×10 6 to 500×10 6naive Treg cells.

[0011] In an embodiment, each unit dose of the therapeutic cell population comprises 0.2×10 6 to 500×10 6 naive Treg cells per kilogram of body weight of the subject receiving the cell graft.

[0012] In various embodiments, each unit dose of the therapeutic cell population comprises 1.0×10 6 to 50×10 6 HSPCs per kilogram of body weight of the subject receiving the cell graft.

[0013] In some embodiments, each unit dose of the therapeutic cell population comprises 1.0×10 6 to 250×10 6 Tmem per kilogram of body weight of the subject receiving the cell graft.

[0014] In an embodiment, each unit dose of the therapeutic cell population comprises less than 1×10 5 naive conventional αβ-T cells per kilogram of body weight of the subject receiving the cell graft.

[0015] In various embodiments, each unit dose of the therapeutic cell population comprises 1×10 6 to 2.5×10 6 Treg cells per kilogram of body weight of the subject receiving the cell graft.

[0016] In some embodiments, the unit dose further comprises 1×10 4 to 200×10 4 iNKT per kilogram of body weight of the subject receiving the cell graft.

[0017] In an embodiment, the pharmaceutical composition is suitable for administration to the subject receiving the cell graft.

[0018] In various embodiments, the pharmaceutical composition further comprises an excipient. In some cases, the excipient is Normosol-R. In some cases, the excipient is human serum.

[0019] In some embodiments, the HSPC is haploidentical to the subject receiving the cell graft.

[0020] In an embodiment, the Treg, Tmem, or a combination thereof is HLA-matched to the subject receiving the cell graft.

[0021] In various embodiments, at least a portion of the therapeutic cell population is autologous to the subject receiving the cell graft.

[0022] In some embodiments, the subject receiving the pharmaceutical composition or the cell graft has received a myeloablative conditioning regimen comprising thiotepa.

[0023] In an embodiment, the subject receiving the pharmaceutical composition or the cell graft is receiving a GVHD prophylaxis regimen comprising tacrolimus.

[0024] In various embodiments, the subject receiving the pharmaceutical composition or the cell graft will receive a GVHD prophylaxis regimen comprising tacrolimus.

[0025] Another aspect of the present disclosure is a pharmaceutical composition comprising a therapeutic cell population that is enriched in hematopoietic stem / progenitor cells (HSPCs), memory T cells (Tmem), and regulatory T cells (Tregs), and wherein the cell population is depleted of naive conventional αβ-T cells, and wherein the ratio of naive conventional αβ-T cells to HSPCs in the therapeutic cell population is less than 1:400, the ratio of naive conventional αβ-T cells to Tmem is less than 1:800, and the ratio of naive conventional αβ-T cells to Tregs is less than 1:5. In this regard, the subject receiving the pharmaceutical composition has received a myeloablative conditioning regimen comprising thiotepa, and / or the subject receiving the cell graft is receiving or will receive a GVHD prophylaxis regimen comprising tacrolimus.

[0026] In some embodiments, the therapeutic cell population further comprises invariant natural killer T cells (iNKTs), and the therapeutic cell population has a ratio of naive conventional αβ-T cells to iNKTs of less than 100:1.

[0027] In an embodiment, the ratio of naive conventional αβ-T cells to Tmem is less than 1:3.

[0028] In various embodiments, the therapeutic cell population has a ratio of naive conventional αβ-T cells to naive Tregs of less than 1:2.

[0029] In some embodiments, the subject receiving the pharmaceutical composition or the cell graft has received a myeloablative conditioning regimen comprising thiotepa.

[0030] In an embodiment, the subject receiving the pharmaceutical composition or the cell graft is receiving a GVHD prophylaxis regimen comprising tacrolimus.

[0031] In various embodiments, the subject receiving the pharmaceutical composition or the cell graft will receive a GVHD prophylaxis regimen that includes tacrolimus.

[0032] It should be understood that the different aspects and / or embodiments of the present disclosure can be understood individually, jointly, or in combination with each other. Any description herein regarding a particular composition and / or method applies to and can be used with any other particular composition and / or method disclosed herein. Additionally, any composition disclosed herein is applicable 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.

[0033] Certain aspects of the present disclosure relate to a cell therapy product comprising a population of cells consisting of isolated CD45 + cells, wherein the population of cells consisting of isolated CD45 + cells comprises: a) a dose of from about 1.0x10 5 to about 1.0x10 8 CD34 + hematopoietic stem and progenitor cells (HSPCs) per kilogram of body weight of a human subject receiving the product or a total dose of from about 5.0x10 5 to about 1.5x10 10 CD34 + hematopoietic stem and progenitor cells (HSPCs); b) a dose of from about 1.0x10 5 to about 1.0x10 8 CD45RA - memory T cells (Tmem) per kilogram of body weight of the human subject receiving the product or a total dose of from about 5.0x10 5 to about 1.5x10 10 CD45RA - memory T cells (Tmem); and c) a dose of from about 1.0x10 5 to about 2.0x10 7 fresh CD4 + CD25 + CD127 dim regulatory T cells (Treg) per kilogram of body weight of the human subject receiving the product or a total dose of from about 5.0x10 5 to about 3.0x10 9 isolated fresh + CD4 + CD25 + CD127 dimThe total dose of regulatory T cells (Tregs), wherein the cell therapy product has depleted naïve conventional CD3 + CD25 - CD45RA + T cells (Tcon), to comprise less than about 5.0x10 5 naïve conventional CD3 + CD25 - CD45RA + T cells (Tcon), less than about 6.0x10 7 total naïve conventional CD3 + CD25 - CD45RA + T cells (Tcon) or less than about 1.0x10 6 total naïve conventional CD3 + CD25 - CD45RA + T cells (Tcon), and wherein the population consisting of isolated CD45 + cells is formulated with an excipient at neutral pH.

[0034] In some embodiments, the dose of the HSPCs comprises the following doses: about 1.0x10 5 or more HSPCs per kilogram of body weight of the human subject receiving the product, about 2.0x10 5 or more HSPCs per kilogram of body weight of the human subject receiving the product, about 3.0x10 5 or more HSPCs per kilogram of body weight of the human subject receiving the product, about 4.0x10 5 or more HSPCs per kilogram of body weight of the human subject receiving the product, about 5.0x10 5 or more HSPCs per kilogram of body weight of the human subject receiving the product, about 6.0x10 5 or more HSPCs per kilogram of body weight of the human subject receiving the product, about 7.0x10 5 or more HSPCs per kilogram of body weight of the human subject receiving the product, about 8.0x10 5 or more HSPCs per kilogram of body weight of the human subject receiving the product, about 9.0x10 5 or more HSPCs per kilogram of body weight of the human subject receiving the product, about 1.0x10 6one or more HSPCs, approximately 1.5x10 per kilogram of body weight of the human subject receiving the product 6 one or more HSPCs, approximately 2.0x10 per kilogram of body weight of the human subject receiving the product 6 one or more HSPCs, approximately 2.5x10 per kilogram of body weight of the human subject receiving the product 6 one or more HSPCs, approximately 3.0x10 per kilogram of body weight of the human subject receiving the product 6 one or more HSPCs, approximately 3.5x10 per kilogram of body weight of the human subject receiving the product 6 one or more HSPCs, approximately 4.0x10 per kilogram of body weight of the human subject receiving the product 6 one or more HSPCs, approximately 4.5x10 per kilogram of body weight of the human subject receiving the product 6 one or more HSPCs, approximately 5.0x10 per kilogram of body weight of the human subject receiving the product 6 one or more HSPCs, approximately 5.5x10 per kilogram of body weight of the human subject receiving the product 6 one or more HSPCs, approximately 6.0x10 per kilogram of body weight of the human subject receiving the product 6 one or more HSPCs, approximately 6.5x10 per kilogram of body weight of the human subject receiving the product 6 one or more HSPCs, approximately 7.0x10 per kilogram of body weight of the human subject receiving the product 6 one or more HSPCs, approximately 7.5x10 per kilogram of body weight of the human subject receiving the product 6 one or more HSPCs, approximately 8.0x10 per kilogram of body weight of the human subject receiving the product 6 one or more HSPCs, approximately 8.5x10 per kilogram of body weight of the human subject receiving the product 6 one or more HSPCs, approximately 9.0x10 per kilogram of body weight of the human subject receiving the product 6 one or more HSPCs, approximately 9.5x10 per kilogram of body weight of the human subject receiving the product 6 one or more HSPCs, approximately 1.0x10 per kilogram of body weight of the human subject receiving the product 7 one or more HSPCs, approximately 1.5x10 per kilogram of body weight of the human subject receiving the product 7one or more HSPCs, about 2.0x10 per kilogram of body weight of the human subject receiving the product 7 one or more HSPCs, about 2.5x10 per kilogram of body weight of the human subject receiving the product 7 one or more HSPCs, about 3.0x10 per kilogram of body weight of the human subject receiving the product 7 one or more HSPCs, about 3.5x10 per kilogram of body weight of the human subject receiving the product 7 one or more HSPCs, about 4.0x10 per kilogram of body weight of the human subject receiving the product 7 one or more HSPCs, about 4.5x10 per kilogram of body weight of the human subject receiving the product 7 one or more HSPCs, about 5.0x10 per kilogram of body weight of the human subject receiving the product 7 one or more HSPCs, about 5.5x10 per kilogram of body weight of the human subject receiving the product 7 one or more HSPCs, about 6.0x10 per kilogram of body weight of the human subject receiving the product 7 one or more HSPCs, about 6.5x10 per kilogram of body weight of the human subject receiving the product 7 one or more HSPCs, about 7.0x10 per kilogram of body weight of the human subject receiving the product 7 one or more HSPCs, about 7.5x10 per kilogram of body weight of the human subject receiving the product 7 one or more HSPCs, about 8.0x10 per kilogram of body weight of the human subject receiving the product 7 one or more HSPCs, about 8.5x10 per kilogram of body weight of the human subject receiving the product 7 one or more HSPCs, about 9.0x10 per kilogram of body weight of the human subject receiving the product 7 one or more HSPCs, about 9.5x10 per kilogram of body weight of the human subject receiving the product 7 one or more HSPCs or about 1.0x10 per kilogram of body weight of the human subject receiving the product 8 one or more HSPCs. In some embodiments that can be combined with any of the foregoing embodiments, the dose of the HSPCs comprises the following total dose: about 5.0x10 5 one or more HSPCs, about 6.0x10 5 one or more HSPCs, about 7.0x10 5one or more HSPCs, approximately 8.0x10 5 one or more HSPCs, approximately 9.0x10 5 one or more HSPCs, approximately 1.0x10 6 one or more HSPCs, approximately 1.5x10 6 one or more HSPCs, approximately 2.0x10 6 one or more HSPCs, approximately 2.5x10 6 one or more HSPCs, approximately 3.0x10 6 one or more HSPCs, approximately 3.5x10 6 one or more HSPCs, approximately 4.0x10 6 one or more HSPCs, approximately 4.5x10 6 one or more HSPCs, approximately 5.0x10 6 one or more HSPCs, approximately 5.5x10 6 one or more HSPCs, approximately 6.0x10 6 one or more HSPCs, approximately 6.5x10 6 one or more HSPCs, approximately 7.0x10 6 one or more HSPCs, approximately 7.5x10 6 one or more HSPCs, approximately 8.0x10 6 one or more HSPCs, approximately 8.5x10 6 one or more HSPCs, approximately 9.0x10 6 one or more HSPCs, approximately 9.5x10 6 one or more HSPCs, approximately 1.0x10 7 one or more HSPCs, approximately 1.5x10 7 one or more HSPCs, approximately 2.0x10 7 one or more HSPCs, approximately 2.5x10 7 one or more HSPCs, approximately 3.0x10 7 one or more HSPCs, approximately 3.5x10 7 one or more HSPCs, approximately 4.0x10 7 one or more HSPCs, approximately 4.5x10 7 one or more HSPCs, approximately 5.0x10 7 one or more HSPCs, approximately 5.5x10 7 one or more HSPCs, approximately 6.0x10 7 one or more HSPCs, approximately 6.5x10 7one or more HSPCs, approximately 7.0x10 7 one or more HSPCs, approximately 7.5x10 7 one or more HSPCs, approximately 8.0x10 7 one or more HSPCs, approximately 8.5x10 7 one or more HSPCs, approximately 9.0x10 7 one or more HSPCs, approximately 9.5x10 7 one or more HSPCs, approximately 1.0x10 8 one or more HSPCs, approximately 1.5x10 8 one or more HSPCs, approximately 2.0x10 8 one or more HSPCs, approximately 2.5x10 8 one or more HSPCs, approximately 3.0x10 8 one or more HSPCs, approximately 3.5x10 8 one or more HSPCs, approximately 4.0x10 8 one or more HSPCs, approximately 4.5x10 8 one or more HSPCs, approximately 5.0x10 8 one or more HSPCs, approximately 5.5x10 8 one or more HSPCs, approximately 6.0x10 8 one or more HSPCs, approximately 6.5x10 8 one or more HSPCs, approximately 7.0x10 8 one or more HSPCs, approximately 7.5x10 8 one or more HSPCs, approximately 8.0x10 8 one or more HSPCs, approximately 8.5x10 8 one or more HSPCs, approximately 9.0x10 8 one or more HSPCs, approximately 9.5x10 8 one or more HSPCs, approximately 1.0x10 9 one or more HSPCs, approximately 1.5x10 9 one or more HSPCs, approximately 2.0x10 9 one or more HSPCs, approximately 2.5x10 9 one or more HSPCs, approximately 3.0x10 9 one or more HSPCs, approximately 3.5x10 9 one or more HSPCs, approximately 4.0x10 9 one or more HSPCs, approximately 4.5x10 9one or more HSPCs, approximately 5.0x10 9 one or more HSPCs, approximately 5.5x10 9 one or more HSPCs, approximately 6.0x10 9 one or more HSPCs, approximately 6.5x10 9 one or more HSPCs, approximately 7.0x10 9 one or more HSPCs, approximately 7.5x10 9 one or more HSPCs, approximately 8.0x10 9 one or more HSPCs, approximately 8.5x10 9 one or more HSPCs, approximately 9.0x10 9 one or more HSPCs, approximately 9.5x10 9 one or more HSPCs, approximately 1.0x10 10 one or more HSPCs or approximately 1.5x10 10 one or more HSPCs. In some embodiments that can be combined with any of the foregoing embodiments, the dose of the Tmem comprises the following doses: approximately 1.0x10 5 per kilogram of body weight of the human subject receiving the product, one or more Tmem, approximately 2.0x10 5 per kilogram of body weight of the human subject receiving the product, one or more Tmem, approximately 3.0x10 5 per kilogram of body weight of the human subject receiving the product, one or more Tmem, approximately 4.0x10 5 per kilogram of body weight of the human subject receiving the product, one or more Tmem, approximately 5.0x10 5 per kilogram of body weight of the human subject receiving the product, one or more Tmem, approximately 6.0x10 5 per kilogram of body weight of the human subject receiving the product, one or more Tmem, approximately 7.0x10 5 per kilogram of body weight of the human subject receiving the product, one or more Tmem, approximately 8.0x10 5 per kilogram of body weight of the human subject receiving the product, one or more Tmem, approximately 9.0x10 5 per kilogram of body weight of the human subject receiving the product, one or more Tmem, approximately 1.0x10 6 per kilogram of body weight of the human subject receiving the product, one or more Tmem, approximately 1.5x10 6one or more Tmems, about 2.0x10 per kilogram of body weight of the human subject receiving the product 6 one or more Tmems, about 2.5x10 per kilogram of body weight of the human subject receiving the product 6 one or more Tmems, about 3.0x10 per kilogram of body weight of the human subject receiving the product 6 one or more Tmems, about 3.5x10 per kilogram of body weight of the human subject receiving the product 6 one or more Tmems, about 4.0x10 per kilogram of body weight of the human subject receiving the product 6 one or more Tmems, about 4.5x10 per kilogram of body weight of the human subject receiving the product 6 one or more Tmems, about 5.0x10 per kilogram of body weight of the human subject receiving the product 6 one or more Tmems, about 5.5x10 per kilogram of body weight of the human subject receiving the product 6 one or more Tmems, about 6.0x10 per kilogram of body weight of the human subject receiving the product 6 one or more Tmems, about 6.5x10 per kilogram of body weight of the human subject receiving the product 6 one or more Tmems, about 7.0x10 per kilogram of body weight of the human subject receiving the product 6 one or more Tmems, about 7.5x10 per kilogram of body weight of the human subject receiving the product 6 one or more Tmems, about 8.0x10 per kilogram of body weight of the human subject receiving the product 6 one or more Tmems, about 8.5x10 per kilogram of body weight of the human subject receiving the product 6 one or more Tmems, about 9.0x10 per kilogram of body weight of the human subject receiving the product 6 one or more Tmems, about 9.5x10 per kilogram of body weight of the human subject receiving the product 6 one or more Tmems, about 1.0x10 per kilogram of body weight of the human subject receiving the product 7 one or more Tmems, about 1.5x10 per kilogram of body weight of the human subject receiving the product 7 one or more Tmems, about 2.0x10 per kilogram of body weight of the human subject receiving the product 7one or more Tmem, about 2.5x10 per kilogram of body weight of the human subject receiving the product 7 one or more Tmem, about 3.0x10 per kilogram of body weight of the human subject receiving the product 7 one or more Tmem, about 3.5x10 per kilogram of body weight of the human subject receiving the product 7 one or more Tmem, about 4.0x10 per kilogram of body weight of the human subject receiving the product 7 one or more Tmem, about 4.5x10 per kilogram of body weight of the human subject receiving the product 7 one or more Tmem, about 5.0x10 per kilogram of body weight of the human subject receiving the product 7 one or more Tmem, about 5.5x10 per kilogram of body weight of the human subject receiving the product 7 one or more Tmem, about 6.0x10 per kilogram of body weight of the human subject receiving the product 7 one or more Tmem, about 6.5x10 per kilogram of body weight of the human subject receiving the product 7 one or more Tmem, about 7.0x10 per kilogram of body weight of the human subject receiving the product 7 one or more Tmem, about 7.5x10 per kilogram of body weight of the human subject receiving the product 7 one or more Tmem, about 8.0x10 per kilogram of body weight of the human subject receiving the product 7 one or more Tmem, about 8.5x10 per kilogram of body weight of the human subject receiving the product 7 one or more Tmem, about 9.0x10 per kilogram of body weight of the human subject receiving the product 7 one or more Tmem, about 9.5x10 per kilogram of body weight of the human subject receiving the product 7 one or more Tmem or about 1.0x10 per kilogram of body weight of the human subject receiving the product 8 one or more Tmem. In some embodiments that can be combined with any of the foregoing embodiments, the dose of the Tmem comprises the following total doses: about 5.0x10 5 one or more Tmem, about 6.0x10 5 one or more Tmem, about 7.0x10 5 one or more Tmem, about 8.0x10 5 one or more Tmem, about 9.0x105 one or more Tmem, approximately 1.0x10 6 one or more Tmem, approximately 1.5x10 6 one or more Tmem, approximately 2.0x10 6 one or more Tmem, approximately 2.5x10 6 one or more Tmem, approximately 3.0x10 6 one or more Tmem, approximately 3.5x10 6 one or more Tmem, approximately 4.0x10 6 one or more Tmem, approximately 4.5x10 6 one or more Tmem, approximately 5.0x10 6 one or more Tmem, approximately 5.5x10 6 one or more Tmem, approximately 6.0x10 6 one or more Tmem, approximately 6.5x10 6 one or more Tmem, approximately 7.0x10 6 one or more Tmem, approximately 7.5x10 6 one or more Tmem, approximately 8.0x10 6 one or more Tmem, approximately 8.5x10 6 one or more Tmem, approximately 9.0x10 6 one or more Tmem, approximately 9.5x10 6 one or more Tmem, approximately 1.0x10 7 one or more Tmem, approximately 1.5x10 7 one or more Tmem, approximately 2.0x10 7 one or more Tmem, approximately 2.5x10 7 one or more Tmem, approximately 3.0x10 7 one or more Tmem, approximately 3.5x10 7 one or more Tmem, approximately 4.0x10 7 one or more Tmem, approximately 4.5x10 7 one or more Tmem, approximately 5.0x10 7 one or more Tmem, approximately 5.5x10 7 one or more Tmem, approximately 6.0x10 7 one or more Tmem, approximately 6.5x10 7 one or more Tmem, approximately 7.0x10 7 one or more Tmem, approximately 7.5x10 7one or more Tmem, approximately 8.0x10 7 one or more Tmem, approximately 8.5x10 7 one or more Tmem, approximately 9.0x10 7 one or more Tmem, approximately 9.5x10 7 one or more Tmem, approximately 1.0x10 8 one or more Tmem, approximately 1.5x10 8 one or more Tmem, approximately 2.0x10 8 one or more Tmem, approximately 2.5x10 8 one or more Tmem, approximately 3.0x10 8 one or more Tmem, approximately 3.5x10 8 one or more Tmem, approximately 4.0x10 8 one or more Tmem, approximately 4.5x10 8 one or more Tmem, approximately 5.0x10 8 one or more Tmem, approximately 5.5x10 8 one or more Tmem, approximately 6.0x10 8 one or more Tmem, approximately 6.5x10 8 one or more Tmem, approximately 7.0x10 8 one or more Tmem, approximately 7.5x10 8 one or more Tmem, approximately 8.0x10 8 one or more Tmem, approximately 8.5x10 8 one or more Tmem, approximately 9.0x10 8 one or more Tmem, approximately 9.5x10 8 one or more Tmem, approximately 1.0x10 9 one or more Tmem, approximately 1.5x10 9 one or more Tmem, approximately 2.0x10 9 one or more Tmem, approximately 2.5x10 9 one or more Tmem, approximately 3.0x10 9 one or more Tmem, approximately 3.5x10 9 one or more Tmem, approximately 4.0x10 9 one or more Tmem, approximately 4.5x10 9 one or more Tmem, approximately 5.0x10 9 one or more Tmem, approximately 5.5x10 9one or more Tmem, approximately 6.0x10 9 one or more Tmem, approximately 6.5x10 9 one or more Tmem, approximately 7.0x10 9 one or more Tmem, approximately 7.5x10 9 one or more Tmem, approximately 8.0x10 9 one or more Tmem, approximately 8.5x10 9 one or more Tmem, approximately 9.0x10 9 one or more Tmem, approximately 9.5x10 9 one or more Tmem, approximately 1.0x10 10 one or more Tmem or approximately 1.5x10 10 one or more Tmem. In some embodiments that can be combined with any of the foregoing embodiments, the dose of the fresh Tregs comprises the following doses: approximately 1.0x10 5 or more fresh Tregs per kilogram of body weight of the human subject receiving the product, approximately 2.0x10 5 or more fresh Tregs per kilogram of body weight of the human subject receiving the product, approximately 3.0x10 5 or more fresh Tregs per kilogram of body weight of the human subject receiving the product, approximately 4.0x10 5 or more fresh Tregs per kilogram of body weight of the human subject receiving the product, approximately 5.0x10 5 or more fresh Tregs per kilogram of body weight of the human subject receiving the product, approximately 6.0x10 5 or more fresh Tregs per kilogram of body weight of the human subject receiving the product, approximately 7.0x10 5 or more fresh Tregs per kilogram of body weight of the human subject receiving the product, approximately 8.0x10 5 or more fresh Tregs per kilogram of body weight of the human subject receiving the product, approximately 9.0x10 5 or more fresh Tregs per kilogram of body weight of the human subject receiving the product, approximately 1.0x10 6 or more fresh Tregs per kilogram of body weight of the human subject receiving the product, approximately 1.5x10 6 or more fresh Tregs per kilogram of body weight of the human subject receiving the product, approximately 2.0x10 6One or more fresh Tregs, approximately 2.5x10 per kilogram of body weight of the human subject receiving the product 6 One or more fresh Tregs, approximately 3.0x10 per kilogram of body weight of the human subject receiving the product 6 One or more fresh Tregs, approximately 3.5x10 per kilogram of body weight of the human subject receiving the product 6 One or more fresh Tregs, approximately 4.0x10 per kilogram of body weight of the human subject receiving the product 6 One or more fresh Tregs, approximately 4.5x10 per kilogram of body weight of the human subject receiving the product 6 One or more fresh Tregs, approximately 5.0x10 per kilogram of body weight of the human subject receiving the product 6 One or more fresh Tregs, approximately 5.5x10 per kilogram of body weight of the human subject receiving the product 6 One or more fresh Tregs, approximately 6.0x10 per kilogram of body weight of the human subject receiving the product 6 One or more fresh Tregs, approximately 6.5x10 per kilogram of body weight of the human subject receiving the product 6 One or more fresh Tregs, approximately 7.0x10 per kilogram of body weight of the human subject receiving the product 6 One or more fresh Tregs, approximately 7.5x10 per kilogram of body weight of the human subject receiving the product 6 One or more fresh Tregs, approximately 8.0x10 per kilogram of body weight of the human subject receiving the product 6 One or more fresh Tregs, approximately 8.5x10 per kilogram of body weight of the human subject receiving the product 6 One or more fresh Tregs, approximately 9.0x10 per kilogram of body weight of the human subject receiving the product 6 One or more fresh Tregs, approximately 9.5x10 per kilogram of body weight of the human subject receiving the product 6 One or more fresh Tregs, approximately 1.0x10 per kilogram of body weight of the human subject receiving the product 7 One or more fresh Tregs, approximately 1.5x10 per kilogram of body weight of the human subject receiving the product 7 One or more fresh Tregs or approximately 2.0x10 per kilogram of body weight of the human subject receiving the product 7one or more fresh Tregs. In some embodiments that may be combined with any of the foregoing embodiments, the dose of the fresh Tregs comprises the following total doses: about 5.0x10 5 one or more fresh Tregs, about 6.0x10 5 one or more fresh Tregs, about 7.0x10 5 one or more fresh Tregs, about 8.0x10 5 one or more fresh Tregs, about 9.0x10 5 one or more fresh Tregs, about 1.0x10 6 one or more fresh Tregs, about 1.5x10 6 one or more fresh Tregs, about 2.0x10 6 one or more fresh Tregs, about 2.5x10 6 one or more fresh Tregs, about 3.0x10 6 one or more fresh Tregs, about 3.5x10 6 one or more fresh Tregs, about 4.0x10 6 one or more fresh Tregs, about 4.5x10 6 one or more fresh Tregs, about 5.0x10 6 one or more fresh Tregs, about 5.5x10 6 one or more fresh Tregs, about 6.0x10 6 one or more fresh Tregs, about 6.5x10 6 one or more fresh Tregs, about 7.0x10 6 one or more fresh Tregs, about 7.5x10 6 one or more fresh Tregs, about 8.0x10 6 one or more fresh Tregs, about 8.5x10 6 one or more fresh Tregs, about 9.0x10 6 one or more fresh Tregs, about 9.5x10 6 one or more fresh Tregs, about 1.0x10 7 one or more fresh Tregs, about 1.5x10 7 one or more fresh Tregs, about 2.0x10 7 one or more fresh Tregs, about 2.5x10 7 one or more fresh Tregs, about 3.0x10 7 one or more fresh Tregs, about 3.5x10 7One or more fresh Tregs, approximately 4.0x10 7 One or more fresh Tregs, approximately 4.5x10 7 One or more fresh Tregs, approximately 5.0x10 7 One or more fresh Tregs, approximately 5.5x10 7 One or more fresh Tregs, approximately 6.0x10 7 One or more fresh Tregs, approximately 6.5x10 7 One or more fresh Tregs, approximately 7.0x10 7 One or more fresh Tregs, approximately 7.5x10 7 One or more fresh Tregs, approximately 8.0x10 7 One or more fresh Tregs, approximately 8.5x10 7 One or more fresh Tregs, approximately 9.0x10 7 One or more fresh Tregs, approximately 9.5x10 7 One or more fresh Tregs, approximately 1.0x10 8 One or more fresh Tregs, approximately 1.5x10 8 One or more fresh Tregs, approximately 2.0x10 8 One or more fresh Tregs, approximately 2.5x10 8 One or more fresh Tregs, approximately 3.0x10 8 One or more fresh Tregs, approximately 3.5x10 8 One or more fresh Tregs, approximately 4.0x10 8 One or more fresh Tregs, approximately 4.5x10 8 One or more fresh Tregs, approximately 5.0x10 8 One or more fresh Tregs, approximately 5.5x10 8 One or more fresh Tregs, approximately 6.0x10 8 One or more fresh Tregs, approximately 6.5x10 8 One or more fresh Tregs, approximately 7.0x10 8 One or more fresh Tregs, approximately 7.5x10 8 One or more fresh Tregs, approximately 8.0x10 8 One or more fresh Tregs, approximately 8.5x10 8 One or more fresh Tregs, approximately 9.0x10 8 One or more fresh Tregs, approximately 9.5x10 8one or more fresh Tregs, about 1.0x10 9 one or more fresh Tregs, about 1.5x10 9 one or more fresh Tregs, about 2.0x10 9 one or more fresh Tregs, about 2.5x10 9 one or more fresh Tregs or about 3.0x10 9 one or more fresh Tregs. In some embodiments that can be combined with any of the foregoing embodiments, the cell therapy product comprises less than about 5.0x10 5 Tcons per kilogram of body weight of the human subject receiving the product, less than about 4.5x10 5 Tcons per kilogram of body weight of the human subject receiving the product, less than about 4.0x10 5 Tcons per kilogram of body weight of the human subject receiving the product, less than about 3.5x10 5 Tcons per kilogram of body weight of the human subject receiving the product, less than about 3.0x10 5 Tcons per kilogram of body weight of the human subject receiving the product, less than about 2.5x10 5 Tcons per kilogram of body weight of the human subject receiving the product, less than about 2.0x10 5 Tcons per kilogram of body weight of the human subject receiving the product, less than about 1.5x10 5 Tcons per kilogram of body weight of the human subject receiving the product, less than about 1.0x10 5 Tcons per kilogram of body weight of the human subject receiving the product, less than about 9.5x10 4 Tcons per kilogram of body weight of the human subject receiving the product, less than about 9.0x10 4 Tcons per kilogram of body weight of the human subject receiving the product, less than about 8.5x10 4 Tcons per kilogram of body weight of the human subject receiving the product, less than about 8.0x10 4 Tcons per kilogram of body weight of the human subject receiving the product, less than about 7.5x10 4 Tcons per kilogram of body weight of the human subject receiving the product, less than about 7.0x10 4 Tcons per kilogram of body weight of the human subject receiving the product, less than about 6.5x10 4Tcons, less than about 6.0x10 per kg of body weight of the human subject receiving the product 4 Tcons, less than about 5.5x10 per kg of body weight of the human subject receiving the product 4 Tcons, less than about 5.0x10 per kg of body weight of the human subject receiving the product 4 Tcons, less than about 4.5x10 per kg of body weight of the human subject receiving the product 4 Tcons, less than about 4.0x10 per kg of body weight of the human subject receiving the product 4 Tcons, less than about 3.5x10 per kg of body weight of the human subject receiving the product 4 Tcons, less than about 3.0x10 per kg of body weight of the human subject receiving the product 4 Tcons, less than about 2.5x10 per kg of body weight of the human subject receiving the product 4 Tcons, less than about 2.0x10 per kg of body weight of the human subject receiving the product 4 Tcons, less than about 1.5x10 per kg of body weight of the human subject receiving the product 4 Tcons, less than about 1.0x10 per kg of body weight of the human subject receiving the product 4 Tcons, less than about 9.5x10 per kg of body weight of the human subject receiving the product 3 Tcons, less than about 9.0x10 per kg of body weight of the human subject receiving the product 3 Tcons, less than about 8.5x10 per kg of body weight of the human subject receiving the product 3 Tcons, less than about 8.0x10 per kg of body weight of the human subject receiving the product 3 Tcons, less than about 7.5x10 per kg of body weight of the human subject receiving the product 3 Tcons, less than about 7.0x10 per kg of body weight of the human subject receiving the product 3 Tcons, less than about 6.5x10 per kg of body weight of the human subject receiving the product 3 Tcons, less than about 6.0x10 per kg of body weight of the human subject receiving the product 3 Tcons, less than about 5.5x10 per kg of body weight of the human subject receiving the product 3Tcons, less than about 5.0x10 per kg body weight of the human subject receiving the product 3 Tcons, less than about 4.5x10 per kg body weight of the human subject receiving the product 3 Tcons, less than about 4.0x10 per kg body weight of the human subject receiving the product 3 Tcons, less than about 3.5x10 per kg body weight of the human subject receiving the product 3 Tcons, less than about 3.0x10 per kg body weight of the human subject receiving the product 3 Tcons, less than about 2.5x10 per kg body weight of the human subject receiving the product 3 Tcons, less than about 2.0x10 per kg body weight of the human subject receiving the product 3 Tcons, less than about 1.5x10 per kg body weight of the human subject receiving the product 3 Tcons or less than about 1.0x10 per kg body weight of the human subject receiving the product 3 Tcons. In some embodiments that can be combined with any of the foregoing embodiments, the cell therapy product comprises less than about 6.0x10 7 total Tcons, less than about 5.5x10 7 total Tcons, less than about 5.0x10 7 total Tcons, less than about 4.5x10 7 total Tcons, less than about 4.0x10 7 total Tcons, less than about 3.5x10 7 total Tcons, less than about 3.0x10 7 total Tcons, less than about 2.5x10 7 total Tcons, less than about 2.0x10 7 total Tcons, less than about 1.5x10 7 total Tcons, less than about 1.0x10 7 total Tcons, less than about 9.5x10 6 total Tcons, less than about 9.0x10 6 total Tcons, less than about 8.5x10 6 total Tcons, less than about 8.0x10 6 total Tcons, less than about 7.5x10 6 total Tcons, less than about 7.0x10 6 total Tcons, less than about 6.5x106 total Tcons, less than about 6.0x10 6 total Tcons, less than about 5.5x10 6 total Tcons, less than about 5.0x10 6 total Tcons, less than about 4.5x10 6 total Tcons, less than about 4.0x10 6 total Tcons, less than about 3.5x10 6 total Tcons, less than about 3.0x10 6 total Tcons, less than about 2.5x10 6 total Tcons, less than about 2.0x10 6 total Tcons, less than about 1.5x10 6 total Tcons or less than about 1.0x10 6 total Tcons. In some embodiments that can be combined with any of the foregoing embodiments, the population consisting of isolated CD45 + cells is formulated in a volume ranging from about 5 mL to about 1 L. In some embodiments that can be combined with any of the foregoing embodiments, the population consisting of isolated CD45 +Populations of cells are formulated in the following volumes: 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 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 combinable with any of the foregoing embodiments, the neutral pH ranges from about 6.8 to about 7.6. In some embodiments combinable with any of the foregoing embodiments, the excipient comprises a transfer buffer. In some embodiments combinable with any of the foregoing embodiments, the transfer buffer comprises from about 120 mEq to about 160 mEq of sodium. In some embodiments combinable with any of the foregoing embodiments, the transfer buffer comprises a total of from about 270 mOsmol / L to about 320 mOsmol / L. In some embodiments combinable with any of the foregoing embodiments, the transfer buffer is selected from: phosphate buffered saline (PBS), human serum, PlasmaLyte, Normosol-R, and any combination thereof. In some embodiments combinable with any of the foregoing embodiments, the transfer buffer further comprises from about 0.1% by volume to about 10% by volume of a human carrier protein. In some embodiments combinable with any of the foregoing embodiments, the human carrier protein is selected from: human serum albumin (HSA), intravenous immunoglobulin (IVIG), AB serum, and any combination thereof. In some embodiments combinable with any of the foregoing embodiments, the isolated CD45 +A population of cells is dispensed in a single-dose transfer bag. In some embodiments that can be combined with any of the foregoing 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 can be combined with any of the foregoing embodiments, the population of + cells separated by CD45 + enriches HSPC, Tmem, and Treg. In some embodiments that can be combined with any of the foregoing embodiments, the population of +Populations of cells comprise the following ratios of Tcon to Tmem: 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 1:6,500, 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 can be combined with any of the foregoing embodiments, the isolated CD45 +A population composed of cells has a ratio of Tcon to Treg 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 1:9,000, 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 can be combined with any of the foregoing embodiments, the population composed of isolated CD45 + A population composed of cells has a ratio of HSPC to Tmem from about 500:1 to about 1:1,000. In some embodiments that can be combined with any of the foregoing embodiments, the population composed of isolated CD45 + A population composed of cells has a ratio of HSPC to Treg from about 100:1 to about 1:30. In some embodiments that can be combined with any of the foregoing embodiments, the population composed of isolated CD45 + A population composed of cells has a ratio of Tmem to Treg from about 2,000:1 to about 1:10. In some embodiments that can be combined with any of the foregoing embodiments, the population composed of isolated CD45 + The population composed of cells further comprises an enriched population composed of TCR Vα24Jα18 + CD127 + invariant natural killer T cells (iNKT). In some embodiments that can be combined with any of the foregoing embodiments, the population composed of isolated CD45 +The population of cells comprises from about 5.0×10 2 to about 2.0×10 6 iNKTs per kilogram of body weight of the human subject receiving the product, or a total dose of from about 2.0x10 3 to about 4.0x10 8 iNKTs. In some embodiments that can be combined with any of the foregoing embodiments, the dose of iNKTs comprises the following doses: about 5.0x10 2 or more iNKTs per kilogram of body weight of the human subject receiving the product, about 6.0x10 2 or more iNKTs per kilogram of body weight of the human subject receiving the product, about 7.0x10 2 or more iNKTs per kilogram of body weight of the human subject receiving the product, about 8.0x10 2 or more iNKTs per kilogram of body weight of the human subject receiving the product, about 9.0x10 2 or more iNKTs per kilogram of body weight of the human subject receiving the product, about 1.0x10 3 or more iNKTs per kilogram of body weight of the human subject receiving the product, about 2.0x10 3 or more iNKTs per kilogram of body weight of the human subject receiving the product, about 3.0x10 3 or more iNKTs per kilogram of body weight of the human subject receiving the product, about 4.0x10 3 or more iNKTs per kilogram of body weight of the human subject receiving the product, about 5.0x10 3 or more iNKTs per kilogram of body weight of the human subject receiving the product, about 6.0x10 3 or more iNKTs per kilogram of body weight of the human subject receiving the product, about 7.0x10 3 or more iNKTs per kilogram of body weight of the human subject receiving the product, about 8.0x10 3 or more iNKTs per kilogram of body weight of the human subject receiving the product, about 9.0x10 3 or more iNKTs per kilogram of body weight of the human subject receiving the product, about 1.0x10 4 or more iNKTs per kilogram of body weight of the human subject receiving the product, about 2.0x10 4or more iNKTs, approximately 3.0x10 per kilogram of the body weight of the human subject receiving the product 4 or more iNKTs, approximately 4.0x10 per kilogram of the body weight of the human subject receiving the product 4 or more iNKTs, approximately 5.0x10 per kilogram of the body weight of the human subject receiving the product 4 or more iNKTs, approximately 6.0x10 per kilogram of the body weight of the human subject receiving the product 4 or more iNKTs, approximately 7.0x10 per kilogram of the body weight of the human subject receiving the product 4 or more iNKTs, approximately 8.0x10 per kilogram of the body weight of the human subject receiving the product 4 or more iNKTs, approximately 9.0x10 per kilogram of the body weight of the human subject receiving the product 4 or more iNKTs, approximately 1.0x10 per kilogram of the body weight of the human subject receiving the product 5 or more iNKTs, approximately 2.0x10 per kilogram of the body weight of the human subject receiving the product 5 or more iNKTs, approximately 3.0x10 per kilogram of the body weight of the human subject receiving the product 5 or more iNKTs, approximately 4.0x10 per kilogram of the body weight of the human subject receiving the product 5 or more iNKTs, approximately 5.0x10 per kilogram of the body weight of the human subject receiving the product 5 or more iNKTs, approximately 6.0x10 per kilogram of the body weight of the human subject receiving the product 5 or more iNKTs, approximately 7.0x10 per kilogram of the body weight of the human subject receiving the product 5 or more iNKTs, approximately 8.0x10 per kilogram of the body weight of the human subject receiving the product 5 or more iNKTs, approximately 9.0x10 per kilogram of the body weight of the human subject receiving the product 5 or more iNKTs, approximately 1.0x10 per kilogram of the body weight of the human subject receiving the product 6 or more iNKTs, approximately 1.5x10 per kilogram of the body weight of the human subject receiving the product 6 or more iNKTs or approximately 2.0x10 per kilogram of the body weight of the human subject receiving the product 6one or more iNKTs. In some embodiments that can be combined with any of the foregoing embodiments, the dose of the iNKTs comprises the following total doses: approximately 2.0x10 3 one or more iNKTs, approximately 3.0x10 3 one or more iNKTs, approximately 4.0x10 3 one or more iNKTs, approximately 5.0x10 3 one or more iNKTs, approximately 6.0x10 3 one or more iNKTs, approximately 7.0x10 3 one or more iNKTs, approximately 8.0x10 3 one or more iNKTs, approximately 9.0x10 3 one or more iNKTs, approximately 1.0x10 4 one or more iNKTs, approximately 2.0x10 4 one or more iNKTs, approximately 3.0x10 4 one or more iNKTs, approximately 4.0x10 4 one or more iNKTs, approximately 5.0x10 4 one or more iNKTs, approximately 6.0x10 4 one or more iNKTs, approximately 7.0x10 4 one or more iNKTs, approximately 8.0x10 4 one or more iNKTs, approximately 9.0x10 4 one or more iNKTs, approximately 1.0x10 5 one or more iNKTs, approximately 2.0x10 5 one or more iNKTs, approximately 3.0x10 5 one or more iNKTs, approximately 4.0x10 5 one or more iNKTs, approximately 5.0x10 5 one or more iNKTs, approximately 6.0x10 5 one or more iNKTs, approximately 7.0x10 5 one or more iNKTs, approximately 8.0x10 5 one or more iNKTs, approximately 9.0x10 5 one or more iNKTs, approximately 1.0x10 6 one or more iNKTs, approximately 1.5x10 6 one or more iNKTs, approximately 2.0x10 6 one or more iNKTs, approximately 2.5x10 6 one or more iNKTs, approximately 3.0x10 6One or more iNKTs, approximately 3.5x10 6 One or more iNKTs, approximately 4.0x10 6 One or more iNKTs, approximately 4.5x10 6 One or more iNKTs, approximately 5.0x10 6 One or more iNKTs, approximately 5.5x10 6 One or more iNKTs, approximately 6.0x10 6 One or more iNKTs, approximately 6.5x10 6 One or more iNKTs, approximately 7.0x10 6 One or more iNKTs, approximately 7.5x10 6 One or more iNKTs, approximately 8.0x10 6 One or more iNKTs, approximately 8.5x10 6 One or more iNKTs, approximately 9.0x10 6 One or more iNKTs, approximately 9.5x10 6 One or more iNKTs, approximately 1.0x10 7 One or more iNKTs, approximately 1.5x10 7 One or more iNKTs, approximately 2.0x10 7 One or more iNKTs, approximately 2.5x10 7 One or more iNKTs, approximately 3.0x10 7 One or more iNKTs, approximately 3.5x10 7 One or more iNKTs, approximately 4.0x10 7 One or more iNKTs, approximately 4.5x10 7 One or more iNKTs, approximately 5.0x10 7 One or more iNKTs, approximately 5.5x10 7 One or more iNKTs, approximately 6.0x10 7 One or more iNKTs, approximately 6.5x10 7 One or more iNKTs, approximately 7.0x10 7 One or more iNKTs, approximately 7.5x10 7 One or more iNKTs, approximately 8.0x10 7 One or more iNKTs, approximately 8.5x10 7 One or more iNKTs, approximately 9.0x10 7 One or more iNKTs, approximately 9.5x10 7 One or more iNKTs, approximately 1.0x10 8one or more iNKTs, about 1.5x10 8 one or more iNKTs, about 2.0x10 8 one or more iNKTs, about 2.5x10 8 one or more iNKTs, about 3.0x10 8 one or more iNKTs, about 3.5x10 8 one or more iNKTs or about 4.0x10 8 one or more iNKTs. In some embodiments that can be combined with any of the foregoing embodiments, the population consisting of isolated CD45 + cells has a ratio of HSPC to iNKT of about 1:2 to about 500,000:1. In some embodiments that can be combined with any of the foregoing embodiments, the population consisting of isolated CD45 + cells has a ratio of iNKT to Tcon that 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 1:20, 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 can be combined with any of the foregoing embodiments, the population consisting of isolated CD45 + cells has a ratio of iNKT to Tmem of about 5:1 to about 1:1,000,000. In some embodiments that can be combined with any of the foregoing embodiments, the HSPC is cKIT + , CD133 + , CD90 + , CD38 - , CD45RA - , Lin - , CD19 - , TCRα - or any combination thereof. In some embodiments that can be combined with any of the foregoing embodiments, the Tmem is CD3 + CD45RO + . In some embodiments that can be combined with any of the foregoing embodiments, the Tmem comprises a population consisting of T central memory cells (T CM ), a population consisting of T effector memory cells (T EM ), a population consisting of T stem cell central memory cells (T SCM ) or any combination thereof. In some embodiments that can be combined with any of the foregoing embodiments, the T CM is CD4 +CD45RO + or CD8 + CD45RO + 。In some embodiments that can be combined with any of the foregoing embodiments, the T CM is CD45RA - , CD62L + , CCR7 + or any combination thereof. In some embodiments that can be combined with any of the foregoing embodiments, the T EM is CD4 + , CD45RO + , CD45RA - , CD62L - , CCR7 - or any combination thereof. In some embodiments that can be combined with any of the foregoing embodiments, the T SCM is CD4 + CD45RA + or CD8 + CD45RA + 。In some embodiments that can be combined with any of the foregoing embodiments, the T SCM is CD95 + , CD122 + , CXCR3 + , LFA-1 + or any combination thereof. In some embodiments that can be combined with any of the foregoing embodiments, the Treg is FoxP3 + 。In some embodiments that can be combined with any of the foregoing embodiments, the Treg comprises a population consisting of naive Treg cells, a population consisting of memory Treg cells, or a population consisting of naive Treg cells and memory Treg cells. In some embodiments that can be combined with any of the foregoing embodiments, the naive Treg cells are CD4 + CD25 + CD127 dim FoxP3 + CD45RA + CD45RO - 。In some embodiments that can be combined with any of the foregoing embodiments, the dose of the Treg comprises from about 2.0x10 5 to about 5.0x10 8 naive Treg cells per kilogram of body weight of the human subject receiving the product or from about 8.0x10 5 to about 1.0x10 11The total dose of naïve Treg cells. In some embodiments that can be combined with any of the foregoing embodiments, the population of isolated CD45 + cells comprises an HSPC to naïve Treg ratio of from about 1:500 to about 100:1. In some embodiments that can be combined with any of the foregoing embodiments, the population of isolated CD45 + cells comprises a Tmem to naïve Treg ratio of from about 3:1 to about 1:10. In some embodiments that can be combined with any of the foregoing embodiments, the population of isolated CD45 + cells comprises a Tcon to naïve Treg ratio that 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, or less than 1:10. In some embodiments that can be combined with any of the foregoing embodiments, the memory Treg cells are CD4 + CD25 + CD127 dim FoxP3 + CD45RA - CD45RO + . In some embodiments that can be combined with any of the foregoing embodiments, the dose of Tregs comprises from about 5.0x10 4 to about 5.0x10 8 memory Treg cells per kilogram of body weight of the human subject receiving the product, or a total dose of from about 2.0x10 5 to about 1.0x10 11 memory Treg cells. In some embodiments that can be combined with any of the foregoing embodiments, the population of isolated CD45 + cells comprises an HSPC to memory Treg ratio of from about 1:500 to about 10,000:1. In some embodiments that can be combined with any of the foregoing embodiments, the population of isolated CD45 + cells comprises a Tmem to memory Treg ratio of from about 27:1 to about 9:10. In some embodiments that can be combined with any of the foregoing embodiments, the population of isolated CD45 +A population composed of cells has a ratio of Tcon to memory Treg 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 can be combined with any of the foregoing embodiments, the Tcon is TCRα + , TCRβ + or TCRα + TCRβ + . In some embodiments that can be combined with any of the foregoing embodiments, the Tcon is CD25 - , CD127 + or CD25 - CD127 + . In some embodiments that can be combined with any of the foregoing embodiments, the Tcon is TCRα + TCRβ + CD45RA + CD45RO - CD25 - CD95 - IL-2Rβ - CD127 + . In some embodiments that can be combined with any of the foregoing embodiments, the iNKT is CD1d-tet + , 6B11 + or CD1d-tet + 6B11 + . In some embodiments that can be combined with any of the foregoing embodiments, the product further comprises a pharmaceutical composition, and the pharmaceutical composition comprises one or more doses of a graft-versus-host disease (GVHD) prophylactic agent. In some embodiments that can be combined with any of the foregoing embodiments, the GVHD prophylactic agent is tacrolimus. In some embodiments that can be combined with any of the foregoing embodiments, 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 the human subject receiving the product. In some embodiments that can be combined with any of the foregoing embodiments, the dose of tacrolimus comprised in the pharmaceutical composition ranges from about 0.01 mg per kilogram of body weight of the human subject receiving the product twice a day to about 0.50 mg per kilogram of body weight of the human subject receiving the product. In some embodiments that can be combined with any of the foregoing embodiments, upon administration of the isolated CD45 +After a population of cells, the tacrolimus is administered in an amount to maintain a target blood level of about 1 ng / mL to about 10 ng / mL in the human subject receiving the product or is administered in an amount to maintain the target blood level in the human subject receiving the product for about 20 days or longer, about 25 days or longer, about 30 days or longer, about 35 days or longer, about 40 days or longer, about 45 days or longer, about 50 days or longer, about 55 days or longer, about 60 days or longer, about 65 days or longer, about 70 days or longer, about 75 days or longer, about 80 days or longer, about 85 days or longer, about 90 days or longer, about 95 days or longer, about 100 days or longer, about 110 days or longer, about 120 days or longer, about 130 days or longer, about 140 days or longer or about 150 days. In some embodiments that can be combined with any of the foregoing embodiments, the population of isolated CD45 + cells in the formulation contains less than about 5 EU to less than about 0.5 EU of endotoxin per mL.

[0035] In some embodiments that can be combined with any of the foregoing embodiments, the HSPC, the Tmem, the Treg, or any combination thereof is obtained from an allogeneic donor that is HLA-matched to the human subject receiving the product. In some embodiments that can be combined with any of the foregoing embodiments, the population of isolated CD45 + cells is from an allogeneic donor that is HLA-matched to the human subject receiving the product. In some embodiments that can be combined with any of the foregoing embodiments, the HSPC, the Tmem, the Treg, or any combination thereof is obtained from an allogeneic donor that has at least one HLA mismatch relative to the human subject receiving the product. In some embodiments that can be combined with any of the foregoing embodiments, the population of isolated CD45 + cells is from an allogeneic donor that has at least one HLA mismatch relative to the human subject receiving the product. In some embodiments that can be combined with any of the foregoing 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 can be combined with any of the foregoing embodiments, the cells having at least one HLA mismatch are from a donor that is 6 / 8 HLA-mismatched to the human subject receiving the product, or the cells having at least one HLA mismatch are from a donor that is 7 / 8 HLA-mismatched to the human subject receiving the product.

[0036] In some embodiments that can be combined with any of the foregoing embodiments, the cells having at least one HLA mismatch are from a donor that is 7 / 8 HLA mismatched relative to the human subject receiving the product. In some embodiments that can be combined with any of the foregoing 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 can be combined with any of the foregoing 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 can be combined with any of the foregoing 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 can be combined with any of the foregoing 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 can be combined with any of the foregoing embodiments, the donor having the 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 while the human subject receiving the product is heterozygous for the HLA allele. In some embodiments that can be combined with any of the foregoing embodiments, the donor having the 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 while the human subject receiving the product is homozygous for the HLA allele. In some embodiments that can be combined with any of the foregoing embodiments, the donor having the at least one HLA mismatch relative 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. In some embodiments that can be combined with any of the foregoing embodiments, the HSPC, the Tmem, the Treg, or any combination thereof is obtained from an allogeneic donor that is haploidentical relative to the human subject receiving the product. In some embodiments that can be combined with any of the foregoing embodiments, the separated CD45 +The population of cells is from an allogeneic donor who is haploidentical to the human subject receiving the product. In some embodiments that can be combined with any of the foregoing embodiments, the allogeneic donor is related to the human subject receiving the product. In some embodiments that can be combined with any of the foregoing embodiments, the allogeneic donor is unrelated to the human subject receiving the product. In some embodiments that can be combined with any of the foregoing embodiments, the weight of the human subject receiving the product is the actual weight. In some embodiments that can be combined with any of the foregoing embodiments, the weight of the human subject receiving the product is the ideal weight. In some embodiments, the cell therapy product of any of the foregoing embodiments or any combination thereof is used in a method for treating a human subject having or suspected of having a hematological malignancy. In some embodiments, the hematological malignancy is selected from: leukemia, acute leukemia, acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), mixed phenotype acute leukemia (MPAL), chronic myelogenous leukemia (CML), multiple myeloma, lymphoma, Hodgkin's lymphoma, non-Hodgkin lymphoma, myelodysplastic syndrome (MDS), myeloproliferative syndrome, myelofibrosis, and blastic plasmacytoid dendritic cell neoplasm (BPDCN). In some embodiments, the cell therapy product of any of the foregoing embodiments or any combination thereof is used in a method for treating a human subject having or suspected of having an autoimmune disorder. In some embodiments, the autoimmune disorder is multiple sclerosis.

[0037] Other aspects of the disclosure relate to a method of treating a human subject having or suspected of having acute leukemia in a state of complete remission, the method comprising administering to the human subject a cell therapy product comprising a population of cells consisting of isolated CD45 + wherein the population of cells consisting of isolated CD45 + cells comprises an enriched population of CD34 + hematopoietic stem and progenitor cells (HSPCs), an enriched population of CD45RA - memory T cells (Tmem), and an enriched population of fresh CD4 + CD25 + CD127 dim regulatory T cells (Tregs), and wherein the population of cells consisting of isolated CD45 + cells has been depleted of naive conventional CD3 + CD25 - CD45RA +T cells (Tcon), less than about 5.0x10 per kilogram of body weight of the human subject receiving the product 5 naive conventional CD3 + CD25 - CD45RA + T cells (Tcon), less than about 6.0x10 7 total naive conventional CD3 + CD25 - CD45RA + T cells (Tcon) or less than about 1.0x10 6 total naive conventional CD3 + CD25 - CD45RA + T cells (Tcon). Other aspects of the present disclosure relate to a method of treating a human subject having or suspected of having acute leukemia in a state of complete remission, the method comprising administering to the human subject a cell therapy product of the present disclosure. In some embodiments that can be combined with any of the foregoing embodiments, the human subject has a blastic burden of about 5% or less in their bone marrow. In some embodiments that can be combined with any of the foregoing embodiments, there are no circulating blasts and / or blasts with Auer rods in the human subject. In some embodiments that can be combined with any of the foregoing embodiments, there is no extramedullary disease in the human subject. In some embodiments that can be combined with any of the foregoing embodiments, the absolute neutrophil count (ANC) of the human subject is about 1.0x10 9 / L or higher. In some embodiments that can be combined with any of the foregoing embodiments, the platelet count of the human subject is about 1.0x10 11 / L or higher. In some embodiments that can be combined with any of the foregoing embodiments, the human subject is not dependent on red blood cell transfusions. In some embodiments that can be combined with any of the foregoing embodiments, the acute leukemia is in a state of complete remission and hematological incomplete recovery. In some embodiments that can be combined with any of the foregoing embodiments, the human subject has residual neutropenia. In some embodiments that can be combined with any of the foregoing embodiments, the absolute neutrophil count (ANC) of the human subject is about 1.0x10 9 / L or lower. In some embodiments that can be combined with any of the foregoing embodiments, the human subject has residual thrombocytopenia. In some embodiments that can be combined with any of the foregoing embodiments, the platelet count of the human subject is about 1.0x10 11 / L or lower.

[0038] Other aspects of the disclosure relate to a method of treating a human subject having or suspected of having active acute leukemia, the method comprising administering to the human subject a cell therapy product comprising a population of cells consisting of isolated CD45 + cells, wherein the population of isolated CD45 + cells comprises an enriched population of CD34 + hematopoietic stem and progenitor cells (HSPCs), an enriched population of CD45RA - memory T cells (Tmem), and an enriched population of freshly isolated CD4 + CD25 + CD127 dim regulatory T cells (Tregs), and wherein the population of isolated CD45 + cells has been depleted of naive conventional CD3 + CD25 - CD45RA + T cells (Tcon) to comprise less than about 5.0 x 10 5 naive conventional CD3 + CD25 - CD45RA + T cells (Tcon) per kilogram of body weight of the human subject receiving the product, less than about 6.0 x 10 7 total naive conventional CD3 + CD25 - CD45RA + T cells (Tcon), or less than about 1.0 x 10 6 total naive conventional CD3 + CD25 - CD45RA + T cells (Tcon). Other aspects of the disclosure relate to a method of treating a human subject having or suspected of having active acute leukemia, the method comprising administering to the human subject a cell therapy product of the disclosure. In some embodiments, which may be combined with any of the foregoing embodiments, the human subject has a bone marrow leukemic blast infiltration of about 10% or less. In some embodiments, which may be combined with any of the foregoing embodiments, the acute leukemia is acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and / or mixed phenotype acute leukemia (MPAL).

[0039] Other aspects of the disclosure relate to a method of treating a human subject having or suspected of having chronic myelogenous leukemia (CML), the method comprising administering to the human subject a cell therapy product comprising a population of cells consisting of isolated CD45 +A cell therapy product of a population of cells, wherein the population of isolated CD45 + cells comprises an enriched population of CD34 + hematopoietic stem and progenitor cells (HSPCs), an enriched population of CD45RA - memory T cells (Tmem), and an enriched population of fresh CD4 + CD25 + CD127 dim regulatory T cells (Tregs), and wherein the population of isolated CD45 + cells has depleted naïve conventional CD3 + CD25 - CD45RA + T cells (Tcon) to contain less than about 5.0 x 10 5 naïve conventional CD3 + CD25 - CD45RA + T cells (Tcon) per kilogram of body weight of the human subject receiving the product, less than about 6.0 x 10 7 total naïve conventional CD3 + CD25 - CD45RA + T cells (Tcon), or less than about 1.0 x 10 6 total naïve conventional CD3 + CD25 - CD45RA + T cells (Tcon). Other aspects of the disclosure relate to a method of treating a human subject having or suspected of having chronic myelogenous leukemia (CML), the method comprising administering to the human subject the cell therapy product of the disclosure. In some embodiments that can be combined with any of the foregoing embodiments, the human subject is in myeloid blast crisis and / or lymphoid blast crisis. In some embodiments that can be combined with any of the foregoing embodiments, the blast crisis is in a state of complete remission. In some embodiments that can be combined with any of the foregoing embodiments, the blast crisis is in a state of complete remission and incomplete hematological recovery. In some embodiments that can be combined with any of the foregoing embodiments, the CML is in the accelerated phase. In some embodiments that can be combined with any of the foregoing embodiments, the CML is in the chronic phase. In some embodiments that can be combined with any of the foregoing embodiments, the chronic phase CML is resistant or intolerant to one or more first-generation or second-generation tyrosine kinase inhibitors (TKIs).

[0040] Other aspects of the present disclosure relate 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 the human subject a cell therapy product comprising a population of cells consisting of isolated CD45 + cells, wherein the population of cells consisting of isolated CD45 + cells comprises an enriched population of CD34 + hematopoietic stem and progenitor cells (HSPCs), an enriched population of CD45RA - memory T cells (Tmem), and an enriched population of freshly isolated CD4 + CD25 + CD127 dim regulatory T cells (Tregs), and wherein the population of cells consisting of isolated CD45 + cells has been depleted of naive conventional CD3 + CD25 - CD45RA + T cells (Tcon) to comprise less than about 5.0 x 10 5 naive conventional CD3 + CD25 - CD45RA + T cells (Tcon) per kilogram of body weight of the human subject receiving the product, less than about 6.0 x 10 7 total naive conventional CD3 + CD25 - CD45RA + T cells (Tcon), or less than about 1.0 x 10 6 total naive conventional CD3 + CD25 - CD45RA + T cells (Tcon). Other aspects of the present disclosure relate to a method of treating a human subject having or suspected of having myelofibrosis, the method comprising administering to the human subject a cell therapy product comprising a population of cells consisting of isolated CD45

[0041] cells, wherein the population of cells consisting of isolated CD45 + cells comprises an enriched population of CD34 + cells comprises an enriched population of CD34 +A population composed of hematopoietic stem and progenitor cells (HSPCs), an enriched population composed of CD45RA - memory T cells (Tmem), and an enriched population composed of fresh CD4 + CD25 + CD127 dim regulatory T cells (Tregs), and wherein the population composed of isolated CD45 + cells has depleted naive conventional CD3 + CD25 - CD45RA + T cells (Tcon), to comprise less than about 5.0 x 10 5 naive conventional CD3 + CD25 - CD45RA + T cells (Tcon), less than about 6.0 x 10 7 total naive conventional CD3 + CD25 - CD45RA + T cells (Tcon), or less than about 1.0 x 10 6 total naive conventional CD3 + CD25 - CD45RA + T cells (Tcon). Other aspects of the present disclosure relate to a method of treating a human subject having or suspected of having myelofibrosis, the method comprising administering to the human subject a cell therapy product of the present disclosure. In some embodiments that can be combined with any of the foregoing embodiments, the myelofibrosis is eligible for standard myeloablative allogeneic hematopoietic stem cell transplantation (alloHSCT). In some embodiments that can be combined with any of the foregoing embodiments, the myelofibrosis is intermediate-risk-2 myelofibrosis or high-risk myelofibrosis. In some embodiments that can be combined with any of the foregoing embodiments, the myelofibrosis is intermediate-risk-1 myelofibrosis associated with high symptom burden, low platelet count, and / or complex cytogenetics.

[0042] Other aspects of the present disclosure relate to a method of treating a human subject having or suspected of having a hematological malignancy, the method comprising administering to the human subject a cell therapy product comprising a population of cells composed of isolated CD45 + cells, wherein the population of cells composed of isolated CD45 + cells comprises an enriched population composed of CD34 + hematopoietic stem and progenitor cells (HSPCs), an enriched population composed of CD45RA -A population consisting of memory T cells (Tmem) and an enriched population consisting of fresh CD4 + CD25 + CD127 dim regulatory T cells (Treg), and wherein the population consisting of isolated CD45 + cells has been depleted of naive conventional CD3 + CD25 - CD45RA + T cells (Tcon), to contain less than about 5.0 x 10 5 naive conventional CD3 + CD25 - CD45RA + T cells (Tcon), less than about 6.0 x 10 7 total naive conventional CD3 + CD25 - CD45RA + T cells (Tcon) or less than about 1.0 x 10 6 total naive conventional CD3 + CD25 - CD45RA + T cells (Tcon).

[0043] In some embodiments that can be combined with any of the foregoing embodiments, the cell therapy product comprises the cell therapy product of the present disclosure. In some embodiments that can be combined with any of the foregoing embodiments, the hematological malignancy is selected from: leukemia, acute leukemia, acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), mixed phenotype acute leukemia (MPAL), chronic myelogenous leukemia (CML), multiple myeloma, lymphoma, Hodgkin's lymphoma, non-Hodgkin lymphoma, myelodysplastic syndrome (MDS), myeloproliferative syndrome, myelofibrosis, and blastic plasmacytoid dendritic cell neoplasm (BPDCN). In some embodiments that can be combined with any of the foregoing embodiments, the method further comprises administering one or more doses of a graft-versus-host disease (GVHD) prophylactic agent. In some embodiments that can be combined with any of the foregoing embodiments, the GVHS prophylactic agent is tacrolimus. In some embodiments that can be combined with any of the foregoing embodiments, the tacrolimus is provided in an amount sufficient to maintain a trough blood level of from about 5 ng / mL to about 10 ng / mL in the human subject. In some embodiments that can be combined with any of the foregoing embodiments, the tacrolimus is provided in a dose ranging from about 0.01 mg to 0.50 mg per kilogram of the body weight of the human subject twice daily. In some embodiments that can be combined with any of the foregoing embodiments, upon administration by CD45 +After a third population of cells, the tacrolimus is administered in an amount to maintain a target blood level of about 1 ng / mL to about 10 ng / mL in the human subject or is administered for about 20 days or longer, about 25 days or longer, about 30 days or longer, about 35 days or longer, about 40 days or longer, about 55 days or longer, about 50 days or longer, about 55 days or longer, about 60 days or longer, about 65 days or longer, about 770 days or longer, about 75 days or longer, about 80 days or longer, about 85 days or longer, about 90 days or longer, about 95 days or longer, about 100 days or longer, about 110 days or longer, about 120 days or longer, about 130 days or longer, about 140 days or longer or about 150 days in an amount to maintain the target blood level in the human subject. In some embodiments that can be combined with any of the foregoing embodiments, the tacrolimus is administered starting about 12 hours to about 24 hours after administration of the cell therapy product. In some embodiments that can be combined with any of the foregoing embodiments, the administration of the tacrolimus is tapered starting about 90 days after the initial administration of the tacrolimus. In some embodiments that can be combined with any of the foregoing embodiments, the administration comprises infusing the population of cells consisting of isolated CD45 + into the human subject. In some embodiments that can be combined with any of the foregoing embodiments, the population of cells consisting of isolated CD45 + comprises about 1.0 x 10 5 to about 1.0 x 10 8 HSPCs per kilogram of the human subject's body weight or about 5.0 x 10 5 to about 1.5 x 10 10 HSPCs. In some embodiments that can be combined with any of the foregoing embodiments, the population of cells consisting of isolated CD45 + comprises about 1.0 x 10 5 or more HSPCs per kilogram of the human subject's body weight, about 2.0 x 10 5 or more HSPCs per kilogram of the human subject's body weight, about 3.0 x 10 5 or more HSPCs per kilogram of the human subject's body weight, about 4.0 x 10 5 or more HSPCs per kilogram of the human subject's body weight, about 5.0 x 10 5 or more HSPCs per kilogram of the human subject's body weight, about 6.0 x 10 5one or more HSPCs, about 7.0x10 per kilogram of the body weight of the human subject 5 one or more HSPCs, about 8.0x10 per kilogram of the body weight of the human subject 5 one or more HSPCs, about 9.0x10 per kilogram of the body weight of the human subject 5 one or more HSPCs, about 1.0x10 per kilogram of the body weight of the human subject 6 one or more HSPCs, about 1.5x10 per kilogram of the body weight of the human subject 6 one or more HSPCs, about 2.0x10 per kilogram of the body weight of the human subject 6 one or more HSPCs, about 2.5x10 per kilogram of the body weight of the human subject 6 one or more HSPCs, about 3.0x10 per kilogram of the body weight of the human subject 6 one or more HSPCs, about 3.5x10 per kilogram of the body weight of the human subject 6 one or more HSPCs, about 4.0x10 per kilogram of the body weight of the human subject 6 one or more HSPCs, about 4.5x10 per kilogram of the body weight of the human subject 6 one or more HSPCs, about 5.0x10 per kilogram of the body weight of the human subject 6 one or more HSPCs, about 5.5x10 per kilogram of the body weight of the human subject 6 one or more HSPCs, about 6.0x10 per kilogram of the body weight of the human subject 6 one or more HSPCs, about 6.5x10 per kilogram of the body weight of the human subject 6 one or more HSPCs, about 7.0x10 per kilogram of the body weight of the human subject 6 one or more HSPCs, about 7.5x10 per kilogram of the body weight of the human subject 6 one or more HSPCs, about 8.0x10 per kilogram of the body weight of the human subject 6 one or more HSPCs, about 8.5x10 per kilogram of the body weight of the human subject 6 one or more HSPCs, about 9.0x10 per kilogram of the body weight of the human subject 6 one or more HSPCs, about 9.5x10 per kilogram of the body weight of the human subject 6 one or more HSPCs, about 1.0x10 per kilogram of the body weight of the human subject 7 one or more HSPCs, about 1.5x10 per kilogram of the body weight of the human subject7 One or more HSPCs, about 2.0x10 per kilogram of the body weight of the human subject 7 One or more HSPCs, about 2.5x10 per kilogram of the body weight of the human subject 7 One or more HSPCs, about 3.0x10 per kilogram of the body weight of the human subject 7 One or more HSPCs, about 3.5x10 per kilogram of the body weight of the human subject 7 One or more HSPCs, about 4.0x10 per kilogram of the body weight of the human subject 7 One or more HSPCs, about 4.5x10 per kilogram of the body weight of the human subject 7 One or more HSPCs, about 5.0x10 per kilogram of the body weight of the human subject 7 One or more HSPCs, about 5.5x10 per kilogram of the body weight of the human subject 7 One or more HSPCs, about 6.0x10 per kilogram of the body weight of the human subject 7 One or more HSPCs, about 6.5x10 per kilogram of the body weight of the human subject 7 One or more HSPCs, about 7.0x10 per kilogram of the body weight of the human subject 7 One or more HSPCs, about 7.5x10 per kilogram of the body weight of the human subject 7 One or more HSPCs, about 8.0x10 per kilogram of the body weight of the human subject 7 One or more HSPCs, about 8.5x10 per kilogram of the body weight of the human subject 7 One or more HSPCs, about 9.0x10 per kilogram of the body weight of the human subject 7 One or more HSPCs, about 9.5x10 per kilogram of the body weight of the human subject 7 One or more HSPCs or about 1.0x10 per kilogram of the body weight of the human subject 8 One or more HSPCs. In some embodiments that can be combined with any of the foregoing embodiments, the population consisting of isolated CD45 + cells contains about 5.0x10 5 One or more HSPCs, about 6.0x10 5 One or more HSPCs, about 7.0x10 5 One or more HSPCs, about 8.0x10 5 One or more HSPCs, about 9.0x10 5 One or more HSPCs, about 1.0x10 6One or more HSPCs, approximately 1.5x10 6 One or more HSPCs, approximately 2.0x10 6 One or more HSPCs, approximately 2.5x10 6 One or more HSPCs, approximately 3.0x10 6 One or more HSPCs, approximately 3.5x10 6 One or more HSPCs, approximately 4.0x10 6 One or more HSPCs, approximately 4.5x10 6 One or more HSPCs, approximately 5.0x10 6 One or more HSPCs, approximately 5.5x10 6 One or more HSPCs, approximately 6.0x10 6 One or more HSPCs, approximately 6.5x10 6 One or more HSPCs, approximately 7.0x10 6 One or more HSPCs, approximately 7.5x10 6 One or more HSPCs, approximately 8.0x10 6 One or more HSPCs, approximately 8.5x10 6 One or more HSPCs, approximately 9.0x10 6 One or more HSPCs, approximately 9.5x10 6 One or more HSPCs, approximately 1.0x10 7 One or more HSPCs, approximately 1.5x10 7 One or more HSPCs, approximately 2.0x10 7 One or more HSPCs, approximately 2.5x10 7 One or more HSPCs, approximately 3.0x10 7 One or more HSPCs, approximately 3.5x10 7 One or more HSPCs, approximately 4.0x10 7 One or more HSPCs, approximately 4.5x10 7 One or more HSPCs, approximately 5.0x10 7 One or more HSPCs, approximately 5.5x10 7 One or more HSPCs, approximately 6.0x10 7 One or more HSPCs, approximately 6.5x10 7 One or more HSPCs, approximately 7.0x10 7 One or more HSPCs, approximately 7.5x10 7 One or more HSPCs, approximately 8.0x10 7One or more HSPCs, approximately 8.5x10 7 One or more HSPCs, approximately 9.0x10 7 One or more HSPCs, approximately 9.5x10 7 One or more HSPCs, approximately 1.0x10 8 One or more HSPCs, approximately 1.5x10 8 One or more HSPCs, approximately 2.0x10 8 One or more HSPCs, approximately 2.5x10 8 One or more HSPCs, approximately 3.0x10 8 One or more HSPCs, approximately 3.5x10 8 One or more HSPCs, approximately 4.0x10 8 One or more HSPCs, approximately 4.5x10 8 One or more HSPCs, approximately 5.0x10 8 One or more HSPCs, approximately 5.5x10 8 One or more HSPCs, approximately 6.0x10 8 One or more HSPCs, approximately 6.5x10 8 One or more HSPCs, approximately 7.0x10 8 One or more HSPCs, approximately 7.5x10 8 One or more HSPCs, approximately 8.0x10 8 One or more HSPCs, approximately 8.5x10 8 One or more HSPCs, approximately 9.0x10 8 One or more HSPCs, approximately 9.5x10 8 One or more HSPCs, approximately 1.0x10 9 One or more HSPCs, approximately 1.5x10 9 One or more HSPCs, approximately 2.0x10 9 One or more HSPCs, approximately 2.5x10 9 One or more HSPCs, approximately 3.0x10 9 One or more HSPCs, approximately 3.5x10 9 One or more HSPCs, approximately 4.0x10 9 One or more HSPCs, approximately 4.5x10 9 One or more HSPCs, approximately 5.0x10 9 One or more HSPCs, approximately 5.5x10 9 One or more HSPCs, approximately 6.0x10 9one or more HSPCs, approximately 6.5x10 9 one or more HSPCs, approximately 7.0x10 9 one or more HSPCs, approximately 7.5x10 9 one or more HSPCs, approximately 8.0x10 9 one or more HSPCs, approximately 8.5x10 9 one or more HSPCs, approximately 9.0x10 9 one or more HSPCs, approximately 9.5x10 9 one or more HSPCs, approximately 1.0x10 10 one or more HSPCs or approximately 1.5x10 10 one or more HSPCs. In some embodiments that can be combined with any of the foregoing embodiments, the population consisting of isolated CD45 + cells contains approximately 1.0x10 5 to approximately 1.0x10 8 Tmem per kilogram of body weight of the human subject receiving the product, approximately 5.0x10 5 to approximately 1.5x10 10 Tmem. In some embodiments that can be combined with any of the foregoing embodiments, the population consisting of isolated CD45 + cells contains approximately 1.0x10 5 or more Tmem per kilogram of body weight of the human subject receiving the product, approximately 2.0x10 5 or more Tmem per kilogram of body weight of the human subject receiving the product, approximately 3.0x10 5 or more Tmem per kilogram of body weight of the human subject receiving the product, approximately 4.0x10 5 or more Tmem per kilogram of body weight of the human subject receiving the product, approximately 5.0x10 5 or more Tmem per kilogram of body weight of the human subject receiving the product, approximately 6.0x10 5 or more Tmem per kilogram of body weight of the human subject receiving the product, approximately 7.0x10 5 or more Tmem per kilogram of body weight of the human subject receiving the product, approximately 8.0x10 5 or more Tmem per kilogram of body weight of the human subject receiving the product, approximately 9.0x10 5one or more Tmem, approximately 1.0x10 per kilogram of body weight of the human subject receiving the product 6 one or more Tmem, approximately 1.5x10 per kilogram of body weight of the human subject receiving the product 6 one or more Tmem, approximately 2.0x10 per kilogram of body weight of the human subject receiving the product 6 one or more Tmem, approximately 2.5x10 per kilogram of body weight of the human subject receiving the product 6 one or more Tmem, approximately 3.0x10 per kilogram of body weight of the human subject receiving the product 6 one or more Tmem, approximately 3.5x10 per kilogram of body weight of the human subject receiving the product 6 one or more Tmem, approximately 4.0x10 per kilogram of body weight of the human subject receiving the product 6 one or more Tmem, approximately 4.5x10 per kilogram of body weight of the human subject receiving the product 6 one or more Tmem, approximately 5.0x10 per kilogram of body weight of the human subject receiving the product 6 one or more Tmem, approximately 5.5x10 per kilogram of body weight of the human subject receiving the product 6 one or more Tmem, approximately 6.0x10 per kilogram of body weight of the human subject receiving the product 6 one or more Tmem, approximately 6.5x10 per kilogram of body weight of the human subject receiving the product 6 one or more Tmem, approximately 7.0x10 per kilogram of body weight of the human subject receiving the product 6 one or more Tmem, approximately 7.5x10 per kilogram of body weight of the human subject receiving the product 6 one or more Tmem, approximately 8.0x10 per kilogram of body weight of the human subject receiving the product 6 one or more Tmem, approximately 8.5x10 per kilogram of body weight of the human subject receiving the product 6 one or more Tmem, approximately 9.0x10 per kilogram of body weight of the human subject receiving the product 6 one or more Tmem, approximately 9.5x10 per kilogram of body weight of the human subject receiving the product 6 one or more Tmem, approximately 1.0x10 per kilogram of body weight of the human subject receiving the product 7One or more Tmem, about 1.5x10 per kilogram of body weight of the human subject receiving the product 7 One or more Tmem, about 2.0x10 per kilogram of body weight of the human subject receiving the product 7 One or more Tmem, about 2.5x10 per kilogram of body weight of the human subject receiving the product 7 One or more Tmem, about 3.0x10 per kilogram of body weight of the human subject receiving the product 7 One or more Tmem, about 3.5x10 per kilogram of body weight of the human subject receiving the product 7 One or more Tmem, about 4.0x10 per kilogram of body weight of the human subject receiving the product 7 One or more Tmem, about 4.5x10 per kilogram of body weight of the human subject receiving the product 7 One or more Tmem, about 5.0x10 per kilogram of body weight of the human subject receiving the product 7 One or more Tmem, about 5.5x10 per kilogram of body weight of the human subject receiving the product 7 One or more Tmem, about 6.0x10 per kilogram of body weight of the human subject receiving the product 7 One or more Tmem, about 6.5x10 per kilogram of body weight of the human subject receiving the product 7 One or more Tmem, about 7.0x10 per kilogram of body weight of the human subject receiving the product 7 One or more Tmem, about 7.5x10 per kilogram of body weight of the human subject receiving the product 7 One or more Tmem, about 8.0x10 per kilogram of body weight of the human subject receiving the product 7 One or more Tmem, about 8.5x10 per kilogram of body weight of the human subject receiving the product 7 One or more Tmem, about 9.0x10 per kilogram of body weight of the human subject receiving the product 7 One or more Tmem, about 9.5x10 per kilogram of body weight of the human subject receiving the product 7 One or more Tmem or about 1.0x10 per kilogram of body weight of the human subject receiving the product 8 One or more Tmem. In some embodiments that can be combined with any of the foregoing embodiments, the population consisting of isolated CD45 + cells contains about 5.0x105 One or more Tmem, approximately 6.0x10 5 One or more Tmem, approximately 7.0x10 5 One or more Tmem, approximately 8.0x10 5 One or more Tmem, approximately 9.0x10 5 One or more Tmem, approximately 1.0x10 6 One or more Tmem, approximately 1.5x10 6 One or more Tmem, approximately 2.0x10 6 One or more Tmem, approximately 2.5x10 6 One or more Tmem, approximately 3.0x10 6 One or more Tmem, approximately 3.5x10 6 One or more Tmem, approximately 4.0x10 6 One or more Tmem, approximately 4.5x10 6 One or more Tmem, approximately 5.0x10 6 One or more Tmem, approximately 5.5x10 6 One or more Tmem, approximately 6.0x10 6 One or more Tmem, approximately 6.5x10 6 One or more Tmem, approximately 7.0x10 6 One or more Tmem, approximately 7.5x10 6 One or more Tmem, approximately 8.0x10 6 One or more Tmem, approximately 8.5x10 6 One or more Tmem, approximately 9.0x10 6 One or more Tmem, approximately 9.5x10 6 One or more Tmem, approximately 1.0x10 7 One or more Tmem, approximately 1.5x10 7 One or more Tmem, approximately 2.0x10 7 One or more Tmem, approximately 2.5x10 7 One or more Tmem, approximately 3.0x10 7 One or more Tmem, approximately 3.5x10 7 One or more Tmem, approximately 4.0x10 7 One or more Tmem, approximately 4.5x10 7 One or more Tmem, approximately 5.0x10 7 One or more Tmem, approximately 5.5x10 7one or more Tmem, approximately 6.0x10 7 one or more Tmem, approximately 6.5x10 7 one or more Tmem, approximately 7.0x10 7 one or more Tmem, approximately 7.5x10 7 one or more Tmem, approximately 8.0x10 7 one or more Tmem, approximately 8.5x10 7 one or more Tmem, approximately 9.0x10 7 one or more Tmem, approximately 9.5x10 7 one or more Tmem, approximately 1.0x10 8 one or more Tmem, approximately 1.5x10 8 one or more Tmem, approximately 2.0x10 8 one or more Tmem, approximately 2.5x10 8 one or more Tmem, approximately 3.0x10 8 one or more Tmem, approximately 3.5x10 8 one or more Tmem, approximately 4.0x10 8 one or more Tmem, approximately 4.5x10 8 one or more Tmem, approximately 5.0x10 8 one or more Tmem, approximately 5.5x10 8 one or more Tmem, approximately 6.0x10 8 one or more Tmem, approximately 6.5x10 8 one or more Tmem, approximately 7.0x10 8 one or more Tmem, approximately 7.5x10 8 one or more Tmem, approximately 8.0x10 8 one or more Tmem, approximately 8.5x10 8 one or more Tmem, approximately 9.0x10 8 one or more Tmem, approximately 9.5x10 8 one or more Tmem, approximately 1.0x10 9 one or more Tmem, approximately 1.5x10 9 one or more Tmem, approximately 2.0x10 9 one or more Tmem, approximately 2.5x10 9 one or more Tmem, approximately 3.0x10 9 one or more Tmem, approximately 3.5x10 9one or more Tmems, approximately 4.0x10 9 one or more Tmems, approximately 4.5x10 9 one or more Tmems, approximately 5.0x10 9 one or more Tmems, approximately 5.5x10 9 one or more Tmems, approximately 6.0x10 9 one or more Tmems, approximately 6.5x10 9 one or more Tmems, approximately 7.0x10 9 one or more Tmems, approximately 7.5x10 9 one or more Tmems, approximately 8.0x10 9 one or more Tmems, approximately 8.5x10 9 one or more Tmems, approximately 9.0x10 9 one or more Tmems, approximately 9.5x10 9 one or more Tmems, approximately 1.0x10 10 one or more Tmems or approximately 1.5x10 10 one or more Tmems. In some embodiments that can be combined with any of the foregoing embodiments, the population consisting of isolated CD45 + cells comprises approximately 1.0x10 5 to approximately 2.0x10 7 fresh Tregs or approximately 5.0x10 5 to approximately 3.0x10 9 fresh Tregs. In some embodiments that can be combined with any of the foregoing embodiments, the population consisting of isolated CD45 + cells comprises approximately 1.0x10 5 or more fresh Tregs, approximately 2.0x10 5 or more fresh Tregs, approximately 3.0x10 5 or more fresh Tregs, approximately 4.0x10 5 or more fresh Tregs, approximately 5.0x10 5 or more fresh Tregs, approximately 6.0x10 5 or more fresh Tregs, approximately 7.0x10 5one or more fresh Tregs, about 8.0x10 per kilogram of the body weight of the human subject 5 one or more fresh Tregs, about 9.0x10 per kilogram of the body weight of the human subject 5 one or more fresh Tregs, about 1.0x10 per kilogram of the body weight of the human subject 6 one or more fresh Tregs, about 1.5x10 per kilogram of the body weight of the human subject 6 one or more fresh Tregs, about 2.0x10 per kilogram of the body weight of the human subject 6 one or more fresh Tregs, about 2.5x10 per kilogram of the body weight of the human subject 6 one or more fresh Tregs, about 3.0x10 per kilogram of the body weight of the human subject 6 one or more fresh Tregs, about 3.5x10 per kilogram of the body weight of the human subject 6 one or more fresh Tregs, about 4.0x10 per kilogram of the body weight of the human subject 6 one or more fresh Tregs, about 4.5x10 per kilogram of the body weight of the human subject 6 one or more fresh Tregs, about 5.0x10 per kilogram of the body weight of the human subject 6 one or more fresh Tregs, about 5.5x10 per kilogram of the body weight of the human subject 6 one or more fresh Tregs, about 6.0x10 per kilogram of the body weight of the human subject 6 one or more fresh Tregs, about 6.5x10 per kilogram of the body weight of the human subject 6 one or more fresh Tregs, about 7.0x10 per kilogram of the body weight of the human subject 6 one or more fresh Tregs, about 7.5x10 per kilogram of the body weight of the human subject 6 one or more fresh Tregs, about 8.0x10 per kilogram of the body weight of the human subject 6 one or more fresh Tregs, about 8.5x10 per kilogram of the body weight of the human subject 6 one or more fresh Tregs, about 9.0x10 per kilogram of the body weight of the human subject 6 one or more fresh Tregs, about 9.5x10 per kilogram of the body weight of the human subject 6 one or more fresh Tregs, about 1.0x10 per kilogram of the body weight of the human subject 7 one or more fresh Tregs, about 1.5x10 per kilogram of the body weight of the human subject7 one or more fresh Tregs or about 2.0 x 10 per kilogram of body weight of the human subject 7 one or more fresh Tregs. In some embodiments that can be combined with any of the foregoing embodiments, the population consisting of isolated CD45 + cells comprises about 5.0 x 10 5 one or more fresh Tregs, about 6.0 x 10 5 one or more fresh Tregs, about 7.0 x 10 5 one or more fresh Tregs, about 8.0 x 10 5 one or more fresh Tregs, about 9.0 x 10 5 one or more fresh Tregs, about 1.0 x 10 6 one or more fresh Tregs, about 1.5 x 10 6 one or more fresh Tregs, about 2.0 x 10 6 one or more fresh Tregs, about 2.5 x 10 6 one or more fresh Tregs, about 3.0 x 10 6 one or more fresh Tregs, about 3.5 x 10 6 one or more fresh Tregs, about 4.0 x 10 6 one or more fresh Tregs, about 4.5 x 10 6 one or more fresh Tregs, about 5.0 x 10 6 one or more fresh Tregs, about 5.5 x 10 6 one or more fresh Tregs, about 6.0 x 10 6 one or more fresh Tregs, about 6.5 x 10 6 one or more fresh Tregs, about 7.0 x 10 6 one or more fresh Tregs, about 7.5 x 10 6 one or more fresh Tregs, about 8.0 x 10 6 one or more fresh Tregs, about 8.5 x 10 6 one or more fresh Tregs, about 9.0 x 10 6 one or more fresh Tregs, about 9.5 x 10 6 one or more fresh Tregs, about 1.0 x 10 7 one or more fresh Tregs, about 1.5 x 10 7 one or more fresh Tregs, about 2.0 x 10 7 one or more fresh Tregs, about 2.5 x 107 one or more fresh Tregs, approximately 3.0x10 7 one or more fresh Tregs, approximately 3.5x10 7 one or more fresh Tregs, approximately 4.0x10 7 one or more fresh Tregs, approximately 4.5x10 7 one or more fresh Tregs, approximately 5.0x10 7 one or more fresh Tregs, approximately 5.5x10 7 one or more fresh Tregs, approximately 6.0x10 7 one or more fresh Tregs, approximately 6.5x10 7 one or more fresh Tregs, approximately 7.0x10 7 one or more fresh Tregs, approximately 7.5x10 7 one or more fresh Tregs, approximately 8.0x10 7 one or more fresh Tregs, approximately 8.5x10 7 one or more fresh Tregs, approximately 9.0x10 7 one or more fresh Tregs, approximately 9.5x10 7 one or more fresh Tregs, approximately 1.0x10 8 one or more fresh Tregs, approximately 1.5x10 8 one or more fresh Tregs, approximately 2.0x10 8 one or more fresh Tregs, approximately 2.5x10 8 one or more fresh Tregs, approximately 3.0x10 8 one or more fresh Tregs, approximately 3.5x10 8 one or more fresh Tregs, approximately 4.0x10 8 one or more fresh Tregs, approximately 4.5x10 8 one or more fresh Tregs, approximately 5.0x10 8 one or more fresh Tregs, approximately 5.5x10 8 one or more fresh Tregs, approximately 6.0x10 8 one or more fresh Tregs, approximately 6.5x10 8 one or more fresh Tregs, approximately 7.0x10 8 one or more fresh Tregs, approximately 7.5x10 8 one or more fresh Tregs, approximately 8.0x10 8 one or more fresh Tregs, approximately 8.5x10 8one or more fresh Tregs, about 9.0x10 8 one or more fresh Tregs, about 9.5x10 8 one or more fresh Tregs, about 1.0x10 9 one or more fresh Tregs, about 1.5x10 9 one or more fresh Tregs, about 2.0x10 9 one or more fresh Tregs, about 2.5x10 9 one or more fresh Tregs, about 3.0x10 9 one or more fresh Tregs. In some embodiments that can be combined with any of the foregoing embodiments, the population consisting of isolated CD45 + cells contains less than about 5.0x10 5 Tcons per kilogram of body weight of the human subject receiving the product, less than about 4.5x10 5 Tcons per kilogram of body weight of the human subject receiving the product, less than about 4.0x10 5 Tcons per kilogram of body weight of the human subject receiving the product, less than about 3.5x10 5 Tcons per kilogram of body weight of the human subject receiving the product, less than about 3.0x10 5 Tcons per kilogram of body weight of the human subject receiving the product, less than about 2.5x10 5 Tcons per kilogram of body weight of the human subject receiving the product, less than about 2.0x10 5 Tcons per kilogram of body weight of the human subject receiving the product, less than about 1.5x10 5 Tcons per kilogram of body weight of the human subject receiving the product, less than about 1.0x10 5 Tcons per kilogram of body weight of the human subject receiving the product, less than about 9.5x10 4 Tcons per kilogram of body weight of the human subject receiving the product, less than about 9.0x10 4 Tcons per kilogram of body weight of the human subject receiving the product, less than about 8.5x10 4 Tcons per kilogram of body weight of the human subject receiving the product, less than about 8.0x10 4 Tcons per kilogram of body weight of the human subject receiving the product, less than about 7.5x10 4Tcons, less than about 7.0x10 per kg of body weight of the human subject receiving the product 4 Tcons, less than about 6.5x10 per kg of body weight of the human subject receiving the product 4 Tcons, less than about 6.0x10 per kg of body weight of the human subject receiving the product 4 Tcons, less than about 5.5x10 per kg of body weight of the human subject receiving the product 4 Tcons, less than about 5.0x10 per kg of body weight of the human subject receiving the product 4 Tcons, less than about 4.5x10 per kg of body weight of the human subject receiving the product 4 Tcons, less than about 4.0x10 per kg of body weight of the human subject receiving the product 4 Tcons, less than about 3.5x10 per kg of body weight of the human subject receiving the product 4 Tcons, less than about 3.0x10 per kg of body weight of the human subject receiving the product 4 Tcons, less than about 2.5x10 per kg of body weight of the human subject receiving the product 4 Tcons, less than about 2.0x10 per kg of body weight of the human subject receiving the product 4 Tcons, less than about 1.5x10 per kg of body weight of the human subject receiving the product 4 Tcons, less than about 1.0x10 per kg of body weight of the human subject receiving the product 4 Tcons, less than about 9.5x10 per kg of body weight of the human subject receiving the product 3 Tcons, less than about 9.0x10 per kg of body weight of the human subject receiving the product 3 Tcons, less than about 8.5x10 per kg of body weight of the human subject receiving the product 3 Tcons, less than about 8.0x10 per kg of body weight of the human subject receiving the product 3 Tcons, less than about 7.5x10 per kg of body weight of the human subject receiving the product 3 Tcons, less than about 7.0x10 per kg of body weight of the human subject receiving the product 3 Tcons, less than about 6.5x10 per kg of body weight of the human subject receiving the product 3Tcons, less than about 6.0x10 per kilogram of body weight of the human subject receiving the product 3 Tcons, less than about 5.5x10 per kilogram of body weight of the human subject receiving the product 3 Tcons, less than about 5.0x10 per kilogram of body weight of the human subject receiving the product 3 Tcons, less than about 4.5x10 per kilogram of body weight of the human subject receiving the product 3 Tcons, less than about 4.0x10 per kilogram of body weight of the human subject receiving the product 3 Tcons, less than about 3.5x10 per kilogram of body weight of the human subject receiving the product 3 Tcons, less than about 3.0x10 per kilogram of body weight of the human subject receiving the product 3 Tcons, less than about 2.5x10 per kilogram of body weight of the human subject receiving the product 3 Tcons, less than about 2.0x10 per kilogram of body weight of the human subject receiving the product 3 Tcons, less than about 1.5x10 per kilogram of body weight of the human subject receiving the product 3 Tcons or less than about 1.0x10 per kilogram of body weight of the human subject receiving the product 3 Tcons. In some embodiments that can be combined with any of the foregoing embodiments, the population consisting of isolated CD45 + cells contains less than about 6.0x10 7 Tcons, less than about 5.5x10 7 Tcons, less than about 5.0x10 7 Tcons, less than about 4.5x10 7 Tcons, less than about 4.0x10 7 Tcons, less than about 3.5x10 7 Tcons, less than about 3.0x10 7 Tcons, less than about 2.5x10 7 Tcons, less than about 2.0x10 7 Tcons, less than about 1.5x10 7 Tcons, less than about 1.0x10 7 Tcons, less than about 9.5x10 6 Tcons, less than about 9.0x10 6 Tcons, less than about 8.5x10 6Tcons, less than about 8.0x10 6 Tcons, less than about 7.5x10 6 Tcons, less than about 7.0x10 6 Tcons, less than about 6.5x10 6 Tcons, less than about 6.0x10 6 Tcons, less than about 5.5x10 6 Tcons, less than about 5.0x10 6 Tcons, less than about 4.5x10 6 Tcons, less than about 4.0x10 6 Tcons, less than about 3.5x10 6 Tcons, less than about 3.0x10 6 Tcons, less than about 2.5x10 6 Tcons, less than about 2.0x10 6 Tcons, less than about 1.5x10 6 Tcons or less than about 1.0x10 6 Tcons. In some embodiments that can be combined with any of the foregoing embodiments, the population consisting of isolated CD45 + cells further comprises a population enriched in invariant natural killer T cells (iNKT) consisting of TCR Vα24Jα18 + CD127 + In some embodiments that can be combined with any of the foregoing embodiments, the population consisting of isolated CD45 + cells comprises from about 5.0×10 2 to about 2.0×10 6 iNKTs per kilogram of body weight of the human subject receiving the product or about 2.0x10 3 to about 4.0x10 8 iNKTs. In some embodiments that can be combined with any of the foregoing embodiments, the population consisting of isolated CD45 + cells comprises about 5.0x10 2 or more iNKTs per kilogram of body weight of the human subject receiving the product, about 6.0x10 2 or more iNKTs per kilogram of body weight of the human subject receiving the product, about 7.0x10 2 or more iNKTs per kilogram of body weight of the human subject receiving the product, about 8.0x10 2one or more iNKTs, approximately 9.0x10 per kg of body weight of the human subject receiving the product 2 one or more iNKTs, approximately 1.0x10 per kg of body weight of the human subject receiving the product 3 one or more iNKTs, approximately 2.0x10 per kg of body weight of the human subject receiving the product 3 one or more iNKTs, approximately 3.0x10 per kg of body weight of the human subject receiving the product 3 one or more iNKTs, approximately 4.0x10 per kg of body weight of the human subject receiving the product 3 one or more iNKTs, approximately 5.0x10 per kg of body weight of the human subject receiving the product 3 one or more iNKTs, approximately 6.0x10 per kg of body weight of the human subject receiving the product 3 one or more iNKTs, approximately 7.0x10 per kg of body weight of the human subject receiving the product 3 one or more iNKTs, approximately 8.0x10 per kg of body weight of the human subject receiving the product 3 one or more iNKTs, approximately 9.0x10 per kg of body weight of the human subject receiving the product 3 one or more iNKTs, approximately 1.0x10 per kg of body weight of the human subject receiving the product 4 one or more iNKTs, approximately 2.0x10 per kg of body weight of the human subject receiving the product 4 one or more iNKTs, approximately 3.0x10 per kg of body weight of the human subject receiving the product 4 one or more iNKTs, approximately 4.0x10 per kg of body weight of the human subject receiving the product 4 one or more iNKTs, approximately 5.0x10 per kg of body weight of the human subject receiving the product 4 one or more iNKTs, approximately 6.0x10 per kg of body weight of the human subject receiving the product 4 one or more iNKTs, approximately 7.0x10 per kg of body weight of the human subject receiving the product 4 one or more iNKTs, approximately 8.0x10 per kg of body weight of the human subject receiving the product 4 one or more iNKTs, approximately 9.0x10 per kg of body weight of the human subject receiving the product 4One or more iNKTs, about 1.0x10 per kg of body weight of the human subject receiving the product 5 One or more iNKTs, about 2.0x10 per kg of body weight of the human subject receiving the product 5 One or more iNKTs, about 3.0x10 per kg of body weight of the human subject receiving the product 5 One or more iNKTs, about 4.0x10 per kg of body weight of the human subject receiving the product 5 One or more iNKTs, about 5.0x10 per kg of body weight of the human subject receiving the product 5 One or more iNKTs, about 6.0x10 per kg of body weight of the human subject receiving the product 5 One or more iNKTs, about 7.0x10 per kg of body weight of the human subject receiving the product 5 One or more iNKTs, about 8.0x10 per kg of body weight of the human subject receiving the product 5 One or more iNKTs, about 9.0x10 per kg of body weight of the human subject receiving the product 5 One or more iNKTs, about 1.0x10 per kg of body weight of the human subject receiving the product 6 One or more iNKTs, about 1.5x10 per kg of body weight of the human subject receiving the product 6 One or more iNKTs or about 2.0x10 per kg of body weight of the human subject receiving the product 6 One or more iNKTs. In some embodiments that can be combined with any of the foregoing embodiments, the population consisting of isolated CD45 + cells comprises about 2.0x10 3 One or more iNKTs, about 3.0x10 3 One or more iNKTs, about 4.0x10 3 One or more iNKTs, about 5.0x10 3 One or more iNKTs, about 6.0x10 3 One or more iNKTs, about 7.0x10 3 One or more iNKTs, about 8.0x10 3 One or more iNKTs, about 9.0x10 3 One or more iNKTs, about 1.0x10 4 One or more iNKTs, about 2.0x10 4 One or more iNKTs, about 3.0x104 one or more iNKTs, approximately 4.0x10 4 one or more iNKTs, approximately 5.0x10 4 one or more iNKTs, approximately 6.0x10 4 one or more iNKTs, approximately 7.0x10 4 one or more iNKTs, approximately 8.0x10 4 one or more iNKTs, approximately 9.0x10 4 one or more iNKTs, approximately 1.0x10 5 one or more iNKTs, approximately 2.0x10 5 one or more iNKTs, approximately 3.0x10 5 one or more iNKTs, approximately 4.0x10 5 one or more iNKTs, approximately 5.0x10 5 one or more iNKTs, approximately 6.0x10 5 one or more iNKTs, approximately 7.0x10 5 one or more iNKTs, approximately 8.0x10 5 one or more iNKTs, approximately 9.0x10 5 one or more iNKTs, approximately 1.0x10 6 one or more iNKTs, approximately 1.5x10 6 one or more iNKTs, approximately 2.0x10 6 one or more iNKTs, approximately 2.5x10 6 one or more iNKTs, approximately 3.0x10 6 one or more iNKTs, approximately 3.5x10 6 one or more iNKTs, approximately 4.0x10 6 one or more iNKTs, approximately 4.5x10 6 one or more iNKTs, approximately 5.0x10 6 one or more iNKTs, approximately 5.5x10 6 one or more iNKTs, approximately 6.0x10 6 one or more iNKTs, approximately 6.5x10 6 one or more iNKTs, approximately 7.0x10 6 one or more iNKTs, approximately 7.5x10 6 one or more iNKTs, approximately 8.0x10 6 one or more iNKTs, approximately 8.5x10 6 one or more iNKTs, approximately 9.0x10 6one or more iNKTs, approximately 9.5x10 6 one or more iNKTs, approximately 1.0x10 7 one or more iNKTs, approximately 1.5x10 7 one or more iNKTs, approximately 2.0x10 7 one or more iNKTs, approximately 2.5x10 7 one or more iNKTs, approximately 3.0x10 7 one or more iNKTs, approximately 3.5x10 7 one or more iNKTs, approximately 4.0x10 7 one or more iNKTs, approximately 4.5x10 7 one or more iNKTs, approximately 5.0x10 7 one or more iNKTs, approximately 5.5x10 7 one or more iNKTs, approximately 6.0x10 7 one or more iNKTs, approximately 6.5x10 7 one or more iNKTs, approximately 7.0x10 7 one or more iNKTs, approximately 7.5x10 7 one or more iNKTs, approximately 8.0x10 7 one or more iNKTs, approximately 8.5x10 7 one or more iNKTs, approximately 9.0x10 7 one or more iNKTs, approximately 9.5x10 7 one or more iNKTs, approximately 1.0x10 8 one or more iNKTs, approximately 1.5x10 8 one or more iNKTs, approximately 2.0x10 8 one or more iNKTs, approximately 2.5x10 8 one or more iNKTs, approximately 3.0x10 8 one or more iNKTs, approximately 3.5x10 8 one or more iNKTs or approximately 4.0x10 8 one or more iNKTs. In some embodiments that can be combined with any of the foregoing embodiments, relative to the human subject, the population consisting of isolated CD45 + cells is from an allogeneic donor having at least one HLA mismatch. In some embodiments that can be combined with any of the foregoing embodiments, the HSPC is cKIT + , CD133 + , CD90 + , CD38- , CD45RA - , Lin - , CD19 - , TCRα - or any combination thereof. In some embodiments that can be combined with any of the foregoing embodiments, the Tmem is CD3 + CD45RO + . In some embodiments that can be combined with any of the foregoing embodiments, the Tmem comprises a population consisting of T central memory cells (T CM ), a population consisting of T effector memory cells (T EM ), a population consisting of T stem cell central memory cells (T SCM ) or any combination thereof. In some embodiments that can be combined with any of the foregoing embodiments, the T CM is CD4 + CD45RO + or CD8 + CD45RO + . In some embodiments that can be combined with any of the foregoing embodiments, the T CM is CD45RA - , CD62L + , CCR7 + or any combination thereof. In some embodiments that can be combined with any of the foregoing embodiments, the T EM is CD4 + , CD45RO + , CD45RA - , CD62L - , CCR7 - or any combination thereof. In some embodiments that can be combined with any of the foregoing embodiments, the T SCM is CD4 + CD45RA + or CD8 + CD45RA + . In some embodiments that can be combined with any of the foregoing embodiments, the T SCM is CD95 + , CD122 + , CXCR3 + , LFA-1 + or any combination thereof. In some embodiments that can be combined with any of the foregoing embodiments, the Treg is FOXP3 +. In some embodiments that can be combined with any of the foregoing embodiments, the Tregs comprise a population consisting of naive Treg cells, a population consisting of memory Treg cells, or a population consisting of naive Treg cells and memory Treg cells. In some embodiments that can be combined with any of the foregoing embodiments, the naive Treg cells are CD4 + CD25 + CD127 dim FoxP3 + CD45RA + CD45RO - . In some embodiments that can be combined with any of the foregoing embodiments, the Tregs comprise from about 2.0x10 5 to about 5.0x10 8 naive Treg cells or from about 8.0x10 5 to about 1.0x10 11 naive Treg cells per kilogram of body weight of the human subject receiving the product. In some embodiments that can be combined with any of the foregoing embodiments, the memory Treg cells are CD4 + CD25 + CD127 dim FoxP3 + CD45RA - CD45RO + . In some embodiments that can be combined with any of the foregoing embodiments, the Tregs comprise from about 5.0x10 4 to about 5.0x10 8 memory Treg cells or from about 2.0x10 5 to about 1.0x10 11 memory Treg cells per kilogram of body weight of the human subject receiving the product. In some embodiments that can be combined with any of the foregoing embodiments, the Tcons are TCRα + 、TCRβ + or TCRα + TCRβ + . In some embodiments that can be combined with any of the foregoing embodiments, the Tcons are CD25 - 、CD127 + or CD25 - CD127 + . In some embodiments that can be combined with any of the foregoing embodiments, the Tcons are TCRα + TCRβ + CD45RA + CD45RO - CD25- CD95 - IL-2Rβ - CD127 + 。In some embodiments that can be combined with any of the foregoing embodiments, the iNKT is CD1d-tet + 、6B11 + or CD1d-tet + 6B11 + 。In some embodiments that can be combined with any of the foregoing embodiments, the population consisting of isolated CD45 + cells contains less than about 5 EU to less than about 0.5 EU of endotoxin per mL of the formulation.

[0044] In some embodiments that can be combined with any of the foregoing embodiments, the HSPC, the Tmem, the Treg, or any combination thereof is obtained from an allogeneic donor HLA-matched to the human subject receiving the product. In some embodiments that can be combined with any of the foregoing embodiments, the population consisting of isolated CD45 + cells is from an allogeneic donor HLA-matched to the human subject receiving the product. In some embodiments that can be combined with any of the foregoing embodiments, the HSPC, the Tmem, the Treg, or any combination thereof is obtained from an allogeneic donor having at least one HLA mismatch to the human subject receiving the product. In some embodiments that can be combined with any of the foregoing embodiments, the population consisting of isolated CD45 +The population of cells is from an allogeneic donor having at least one HLA mismatch relative to the human subject receiving the product. In some embodiments, which can be combined with any of the foregoing 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, which can be combined with any of the foregoing embodiments, the cells having at least one HLA mismatch are from a donor that is 6 / 8 HLA mismatched relative to the human subject receiving the product, or the cells having at least one HLA mismatch are from a donor that is 7 / 8 HLA mismatched relative to the human subject receiving the product. In some embodiments, which can be combined with any of the foregoing embodiments, the cells having at least one HLA mismatch are from a donor that is 7 / 8 HLA mismatched relative to the human subject receiving the product. In some embodiments, which can be combined with any of the foregoing 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, which can be combined with any of the foregoing 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, which can be combined with any of the foregoing 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, which can be combined with any of the foregoing 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, which can be combined with any of the foregoing embodiments, the donor having the 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 while the human subject receiving the product is heterozygous for the HLA allele. In some embodiments, which can be combined with any of the foregoing embodiments, the donor having the 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 while the human subject receiving the product is homozygous for the HLA allele. In some embodiments, which can be combined with any of the foregoing embodiments, the donor having the at least one HLA mismatch relative 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.In some embodiments that can be combined with any of the foregoing embodiments, the HSPC, the Tmem, the Treg, or any combination thereof is obtained from an allogeneic donor who is haploidentical to the human subject receiving the product. In some embodiments that can be combined with any of the foregoing embodiments, the population of isolated CD45 + cells is from an allogeneic donor who is haploidentical to the human subject receiving the product. In some embodiments that can be combined with any of the foregoing embodiments, the allogeneic donor is related to the human subject receiving the product. In some embodiments that can be combined with any of the foregoing embodiments, the allogeneic donor is unrelated to the human subject receiving the product.

[0045] In some embodiments that can be combined with any of the foregoing embodiments, the method further comprises collecting one or more mobilized peripheral blood donations from the donor. In some embodiments that can be combined with any of the foregoing embodiments, the peripheral blood donation is mobilized by granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), plerixafor, or any combination thereof. In some embodiments that can be combined with any of the foregoing embodiments, at least one of the mobilized peripheral blood donations is processed and sorted using one or more immunoisolation particles (ISPs) to enrich for HSPC, Tmem, and Treg. In some embodiments that can be combined with any of the foregoing embodiments, the one or more ISPs comprise an affinity reagent. In some embodiments that can be combined with any of the foregoing embodiments, the affinity reagent is an immunomagnetic separation particle. In some embodiments that can be combined with any of the foregoing embodiments, the immunomagnetic separation particles are antibodies conjugated to iron-containing particles, respectively. In some embodiments that can be combined with any of the foregoing embodiments, the affinity reagent comprises a plurality of CD34 reagents that bind to CD34 on HSPC. In some embodiments that can be combined with any of the foregoing embodiments, the isolated CD45 + average number of ISPs per HSPC in the population of cells is equal to or less than about 20,000. In some embodiments that can be combined with any of the foregoing embodiments, the isolated CD45 +The average number of ISPs per HSPC in the population of cells is from about 1,000 to about 20,000. In some embodiments that can be combined with any of the foregoing embodiments, the affinity reagent comprises a plurality of CD45RA reagents that bind to one or more CD45RA receptors on Tmem. In some embodiments that can be combined with any of the foregoing embodiments, the affinity reagent comprises a plurality of CD25 reagents that bind to one or more CD25 receptors on Treg. In some embodiments that can be combined with any of the foregoing embodiments, the separated CD45 + The average number of ISPs per Treg in the population of cells is equal to or less than about 4,000. In some embodiments that can be combined with any of the foregoing embodiments, the separated CD45 +The average number of ISPs per Treg in the population of cells is from about 1,500 to about 2,500. In some embodiments that can be combined with any of the foregoing embodiments, the method further comprises administering a conditioning regimen prior to administering the cell therapy product. In some embodiments that can be combined with any of the foregoing embodiments, the conditioning regimen is administered from about two days to about ten days prior to administering the multi-component cell therapy. In some embodiments that can be combined with any of the foregoing embodiments, the conditioning regimen is a total body irradiation (TBI-based) regimen or a total lymphoid irradiation (TLI-based) regimen. In some embodiments that can be combined with any of the foregoing embodiments, the TBI-based regimen comprises fractionated total body irradiation. In some embodiments that can be combined with any of the foregoing embodiments, the fractionated total body irradiation comprises 2 or more, 3 or more, 4 or more, 5 or more, 6 or more, 7 or more, 8 or more, 9 or more, 10 or more, 11 or more, 12 or more, 13 or more, 14 or more, or 15 or more doses. In some embodiments that can be combined with any of the foregoing embodiments, the fractionated total body irradiation comprises a total dose ranging from about 500 cGy to about 1,600 cGy. In some embodiments that can be combined with any of the foregoing embodiments, the TBI-based regimen further comprises one or more conditioning agents. In some embodiments that can be combined with any of the foregoing embodiments, the one or more conditioning agents are selected from: cyclophosphamide, etoposide, fludarabine, thiotepa, antithymocyte globulin (ATG), and any combination thereof. In some embodiments that can be combined with any of the foregoing embodiments, the conditioning regimen is a myeloablative conditioning regimen. In some embodiments that can be combined with any of the foregoing embodiments, the myeloablative conditioning regimen comprises one or more conditioning agents. In some embodiments that can be combined with any of the foregoing embodiments, the one or more conditioning agents are selected from: thiotepa, busulfan, melphalan, fludarabine, cyclophosphamide, antithymocyte globulin (ATG), and any combination thereof. In some embodiments that can be combined with any of the foregoing embodiments, the myeloablative conditioning regimen comprises three or more conditioning agents, wherein at least one conditioning agent comprises thiotepa. In some embodiments that can be combined with any of the foregoing embodiments, the myeloablative conditioning regimen comprises one or more doses of busulfan, fludarabine, and thiotepa.In some embodiments that can be combined with any of the foregoing embodiments, the one or more doses of busulfan, fludarabine, and thiotepa each comprise from about 5 mg to about 12 mg of thiotepa per kilogram of the body weight of the human subject, from about 7 mg to about 11 mg of busulfan per kilogram of the body weight of the human subject, and from about 100 mg to about 200 mg of fludarabine per square meter of body surface area.

[0046] In some embodiments that can be combined with any of the foregoing embodiments, the overall survival rate at 12 months or more after administration of the cell therapy product ranges from about 75% to about 100%. In some embodiments that can be combined with any of the foregoing embodiments, the overall survival rate of the human subject increases after administration of the cell therapy product relative to a corresponding human subject who has received a standard myeloablative allogeneic hematopoietic stem cell transplantation (alloHSCT). In some embodiments that can be combined with any of the foregoing embodiments, the graft-versus-host disease-free and relapse-free survival rate (GFRS) at 12 months or more after administration of the cell therapy product ranges from about 65% to about 100%. In some embodiments that can be combined with any of the foregoing embodiments, the graft-versus-host disease-free and relapse-free survival rate (GFRS) of the human subject increases after administration of the cell therapy product relative to a corresponding human subject who has received a standard myeloablative allogeneic hematopoietic stem cell transplantation (alloHSCT). In some embodiments that can be combined with any of the foregoing embodiments, the relapse-free survival rate at 12 months or more after administration of the cell therapy product ranges from about 70% to about 100%. In some embodiments that can be combined with any of the foregoing embodiments, the relapse-free survival rate of the human subject increases after administration of the cell therapy product relative to a corresponding human subject who has received a standard myeloablative allogeneic hematopoietic stem cell transplantation (alloHSCT). In some embodiments that can be combined with any of the foregoing embodiments, the incidence of acute graft-versus-host disease at 100 days or more after administration of the cell therapy product ranges from about 9% to about 31%. In some embodiments that can be combined with any of the foregoing embodiments, the incidence of chronic graft-versus-host disease at 100 days or more after administration of the cell therapy product ranges from about 1% to about 10%. In some embodiments that can be combined with any of the foregoing embodiments, the incidence of post-transplant lymphoproliferative disorder (PTLD) at 100 days or more after administration of the cell therapy product ranges from about 1% to about 10%. In some embodiments that can be combined with any of the foregoing embodiments, the incidence of grade 2 or higher infections at 100 days or more after administration of the cell therapy product ranges from about 23% to about 31%.

[0047] Other aspects of the present disclosure relate to a method of treating a human subject having or suspected of having multiple sclerosis, the method comprising administering to the human subject a cell therapy product comprising a population of cells consisting of isolated CD45 + cells, wherein the population of cells consisting of isolated CD45 + cells comprises an enriched population of CD34 + hematopoietic stem and progenitor cells (HSPCs), an enriched population of CD45RA - memory T cells (Tmem), and an enriched population of fresh CD4 + CD25 + CD127 dim regulatory T cells (Tregs), and wherein the population of cells consisting of isolated CD45 + cells has been depleted of naive conventional CD3 + CD25 - CD45RA + T cells (Tcon) to comprise less than about 5.0 x 10 5 naive conventional CD3 + CD25 - CD45RA + T cells (Tcon) per kilogram of body weight of the human subject receiving the product, less than about 6.0 x 10 7 total naive conventional CD3 + CD25 - CD45RA + T cells (Tcon), or less than about 1.0 x 10 6 total naive conventional CD3 + CD25 - CD45RA + T cells (Tcon). Other aspects of the present disclosure relate to a method of treating a human subject having or suspected of having multiple sclerosis, the method comprising administering to the human subject the 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 relapsing multiple sclerosis.

[0048] In some embodiments combinable with any of the foregoing embodiments, the age of the human subject is about 3 months or greater. In some embodiments combinable with any of the foregoing embodiments, the age of the human subject is between about 3 months and about 18 years. In some embodiments combinable with any of the foregoing embodiments, the age of the human subject is about 12 years or greater. In some embodiments combinable with any of the foregoing embodiments, the age of the human subject is between about 12 years and about 65 years. In some embodiments combinable with any of the foregoing embodiments, the age of the human subject is between about 12 years and about 75 years. In some embodiments combinable with any of the foregoing embodiments, the age of the human subject is from about 65 years to about 75 years. In some embodiments combinable with any of the foregoing embodiments, the age of the human subject is between about 3 months and about 75 years. In some embodiments combinable with any of the foregoing embodiments, the human subject has received one to five prior lines of therapy.

[0049] Other aspects of the present disclosure relate to a cell therapy kit that comprises the cell therapy product of the present disclosure. Other aspects of the present disclosure relate to a cell therapy kit that comprises a population of isolated CD45 + cells, wherein the population of isolated CD45 + cells comprises: a) a dose of from about 1.0x10 5 to about 1.0x10 8 CD34 + hematopoietic stem and progenitor cells (HSPCs) per kilogram of body weight of the human subject receiving the product or a total dose of from about 5.0x10 5 to about 1.5x10 10 CD34 + hematopoietic stem and progenitor cells (HSPCs); b) a dose of from about 1.0x10 5 to about 1.0x10 8 CD45RA - memory T cells (Tmem) per kilogram of body weight of the human subject receiving the product or a total dose of from about 5.0x10 5 to about 1.5x10 10 CD45RA - memory T cells (Tmem); and c) from about 1.0x10 5 to about 2.0x10 7 fresh CD4 + CD25+ CD127 dim the dose of regulatory T cells (Tregs) or about 5.0x10 5 to about 3.0x10 9 isolated fresh + CD4 + CD25 + CD127 dim the total dose of regulatory T cells (Tregs), wherein the population consisting of isolated CD45 + has depleted naïve conventional CD3 + CD25 - CD45RA + T cells (Tcon), to contain less than about 5.0x10 5 naïve conventional CD3 + CD25 - CD45RA + T cells (Tcon), less than about 6.0x10 7 total naïve conventional CD3 + CD25 - CD45RA + T cells (Tcon) or less than about 1.0x10 6 total naïve conventional CD3 + CD25 - CD45RA + T cells (Tcon), and wherein the population consisting of isolated CD45 + cells is formulated with an excipient at neutral pH. Other aspects of the present disclosure relate to a cell therapy kit, the cell therapy kit comprising a container, the container comprising a population consisting of isolated CD45 + cells, wherein the population consisting of isolated CD45 + cells comprises: a) a dose of about 1.0x10 5 to about 1.0x10 8 CD34 + hematopoietic stem and progenitor cells (HSPCs) or about 5.0x10 5 to about 1.5x10 10 CD34 + hematopoietic stem and progenitor cells (HSPCs); b) about 1.0x10 5 to about 1.0x10 8 CD45RA -The dose of memory T cells (Tmem) or about 5.0x10 5 to about 1.5x10 10 CD45RA - total dose of memory T cells (Tmem); and c) about 1.0x10 5 to about 2.0x10 7 fresh CD4 + CD25 + CD127 dim The dose of regulatory T cells (Treg) or about 5.0x10 5 to about 3.0x10 9 isolated fresh + CD4 + CD25 + CD127 dim total dose of regulatory T cells (Treg), wherein the population consisting of isolated CD45 + has depleted naïve conventional CD3 + CD25 - CD45RA + T cells (Tcon), to contain less than about 5.0x10 5 naïve conventional CD3 + CD25 - CD45RA + T cells (Tcon), less than about 6.0x10 7 total naïve conventional CD3 + CD25 - CD45RA + T cells (Tcon) or less than about 1.0x10 6 total naïve conventional CD3 + CD25 - CD45RA + T cells (Tcon), and wherein the population consisting of isolated CD45 +The population of cells is formulated with an excipient at neutral pH. In some embodiments, which can be combined with any of the foregoing embodiments, the kit further comprises written instructions for treating a hematological malignancy in a human subject using the cell therapy. In some embodiments, which can be combined with any of the foregoing embodiments, the hematological malignancy is selected from: leukemia, acute leukemia, acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), mixed phenotype acute leukemia (MPAL), chronic myelogenous leukemia (CML), multiple myeloma, lymphoma, Hodgkin lymphoma, non-Hodgkin lymphoma, myelodysplastic syndrome (MDS), myeloproliferative syndrome, myelofibrosis, and blastic plasmacytoid dendritic cell neoplasm (BPDCN). In some embodiments, which can be combined with any of the foregoing embodiments, the kit further comprises written instructions for treating multiple sclerosis in a human subject using the cell therapy.

[0050] Other aspects of the disclosure relate to a unit dose that comprises the cell therapy product of the disclosure. Other aspects of the disclosure relate to a unit dose that comprises a population of isolated CD45 + cells, wherein the population of isolated CD45 + cells comprises: a) a total dose of from about 1.0x10 5 to about 1.0x10 8 CD34 + hematopoietic stem and progenitor cells (HSPCs) or from about 5.0x10 5 to about 1.5x10 10 CD34 + hematopoietic stem and progenitor cells (HSPCs) per kilogram of body weight of the human subject receiving the product; b) a dose of from about 1.0x10 5 to about 1.0x10 8 CD45RA - memory T cells (Tmem) or from about 5.0x10 5 to about 1.5x10 10 CD45RA - memory T cells (Tmem) per kilogram of body weight of the human subject receiving the product; and / or c) a total dose of from about 1.0x10 5 to about 2.0x10 7 fresh CD4 + CD25 + CD127 dim regulatory T cells (Tregs) or from about 5.0x10 5from about 1.0x10 9 to about 3.0x10 + isolated fresh + CD4 + CD25 dim CD127 + total dose of regulatory T cells (Tregs), and wherein the population consisting of isolated CD45 + cells has been depleted of naive conventional CD3 - CD25 + CD45RA 5 T cells (Tcon), to contain less than about 5.0x10 + per kilogram of body weight of the human subject receiving the product - naive conventional CD3 + CD25 7 CD45RA + T cells (Tcon), less than about 6.0x10 - total naive conventional CD3 + CD25 6 CD45RA + T cells (Tcon) or less than about 1.0x10 - total naive conventional CD3 + CD25 + CD45RA 5 T cells (Tcon). In some embodiments, the population consisting of isolated CD45 8 cells further comprises one or more excipients. Other aspects of the disclosure relate to a unit dose comprising: a) from about 1.0x10 + to about 1.0x10 5 CD34 10 hematopoietic stem and progenitor cells (HSPCs) or about 5.0x10 + to about 1.5x10 5 total dose of CD34 8 hematopoietic stem and progenitor cells (HSPCs), and one or more excipients; b) from about 1.0x10 - to about 1.0x10 5 CD45RA 10 memory T cells (Tmem) or about 5.0x10 -The total dose of memory T cells (Tmem), and one or more excipients; and c) per kilogram of body weight of the human subject receiving the product, approximately 1.0x10 5 to approximately 2.0x10 7 fresh CD4 + CD25 + CD127 dim regulatory T cells (Treg) or approximately 5.0x10 5 to approximately 3.0x10 9 isolated fresh + CD4 + CD25 + CD127 dim total dose of regulatory T cells (Treg), and one or more excipients, wherein the unit dose has depleted naïve conventional CD3 + CD25 - CD45RA + T cells (Tcon), to contain per kilogram of body weight of the human subject receiving the product less than approximately 5.0x10 5 naïve conventional CD3 + CD25 - CD45RA + T cells (Tcon), less than approximately 6.0x10 7 total naïve conventional CD3 + CD25 - CD45RA + T cells (Tcon) or less than approximately 1.0x10 6 total naïve conventional CD3 + CD25 - CD45RA + T cells (Tcon).

[0051] Other aspects of the disclosure relate to an article of manufacture comprising the cell therapy product of the disclosure. Other aspects of the disclosure relate to an article of manufacture comprising a population of isolated CD45 + cells, wherein the population of isolated CD45 + cells comprises: a) per kilogram of body weight of the human subject receiving the product, approximately 1.0x10 5 to approximately 1.0x10 8 CD34 + hematopoietic stem and progenitor cells (HSPC) or approximately 5.0x10 5 to approximately 1.5x10 10 CD34 +Total dose of hematopoietic stem and progenitor cells (HSPC); b) from about 1.0x10 5 to about 1.0x10 8 CD45RA - memory T cells (Tmem) or from about 5.0x10 5 to about 1.5x10 10 CD45RA - memory T cells (Tmem); and c) from about 1.0x10 5 to about 2.0x10 7 fresh CD4 + CD25 + CD127 dim regulatory T cells (Treg) or from about 5.0x10 5 to about 3.0x10 9 isolated fresh + CD4 + CD25 + CD127 dim regulatory T cells (Treg), wherein the population consisting of isolated CD45 + has depleted naïve conventional CD3 + CD25 - CD45RA + T cells (Tcon) to contain less than about 5.0x10 5 naïve conventional CD3 + CD25 - CD45RA + T cells (Tcon), less than about 6.0x10 7 total naïve conventional CD3 + CD25 - CD45RA + T cells (Tcon) or less than about 1.0x10 6 total naïve conventional CD3 + CD25 - CD45RA + T cells (Tcon), and wherein the population consisting of isolated CD45 + cells is formulated with an excipient at neutral pH. Other aspects of the disclosure relate to an article of manufacture comprising a container containing a population consisting of isolated CD45 + cells, wherein the population consisting of isolated CD45+ A population of cells comprises: a) a dose of from about 1.0x10 5 to about 1.0x10 8 CD34 + hematopoietic stem and progenitor cells (HSPCs) per kilogram of body weight of a human subject receiving the product or a total dose of from about 5.0x10 5 to about 1.5x10 10 CD34 + hematopoietic stem and progenitor cells (HSPCs); b) a dose of from about 1.0x10 5 to about 1.0x10 8 CD45RA - memory T cells (Tmem) per kilogram of body weight of a human subject receiving the product or a total dose of from about 5.0x10 5 to about 1.5x10 10 CD45RA - memory T cells (Tmem); and c) a dose of from about 1.0x10 5 to about 2.0x10 7 fresh CD4 + CD25 + CD127 dim regulatory T cells (Treg) per kilogram of body weight of a human subject receiving the product or a total dose of from about 5.0x10 5 to about 3.0x10 9 isolated fresh + CD4 + CD25 + CD127 dim regulatory T cells (Treg), wherein the population consisting of isolated CD45 + has been depleted of naive conventional CD3 + CD25 - CD45RA + T cells (Tcon) to contain less than about 5.0x10 5 naive conventional CD3 + CD25 - CD45RA + T cells (Tcon), less than about 6.0x10 7 total naive conventional CD3 + CD25 - CD45RA + T cells (Tcon) or less than about 1.0x10 6 total naive conventional CD3+ CD25 - CD45RA + T cells (Tcon), and wherein the population consisting of isolated CD45 + cells is formulated with an excipient at neutral pH. In some embodiments that can be combined with any of the foregoing embodiments, the product further comprises instructions for administering the product to a human subject for the treatment of hematological malignancies. In some embodiments that can be combined with any of the foregoing embodiments, the hematological malignancies are selected from: leukemia, acute leukemia, acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), mixed phenotype acute leukemia (MPAL), chronic myelogenous leukemia (CML), multiple myeloma, lymphoma, Hodgkin's lymphoma, non-Hodgkin lymphoma, myelodysplastic syndrome (MDS), myeloproliferative syndrome, myelofibrosis, and blastic plasmacytoid dendritic cell neoplasm (BPDCN). In some embodiments that can be combined with any of the foregoing embodiments, the product further comprises instructions for administering the product to a human subject for the treatment of multiple sclerosis.

[0052] Other aspects of the present disclosure relate to a container that contains the cell therapy product of the present disclosure. Other aspects of the present disclosure relate to a container that contains a population consisting of isolated CD45 + cells, wherein the population consisting of isolated CD45 + cells comprises: a) a dose of from about 1.0x10 5 to about 1.0x10 8 CD34 + hematopoietic stem and progenitor cells (HSPCs) per kilogram of body weight of the human subject receiving the product or a total dose of from about 5.0x10 5 to about 1.5x10 10 CD34 + hematopoietic stem and progenitor cells (HSPCs); b) a dose of from about 1.0x10 5 to about 1.0x10 8 CD45RA - memory T cells (Tmem) per kilogram of body weight of the human subject receiving the product or a total dose of from about 5.0x10 5 to about 1.5x10 10 CD45RA - memory T cells (Tmem); and c) from about 1.0x10 5 to about 2.0x10 7 fresh CD4 per kilogram of body weight of the human subject receiving the product+ CD25 + CD127 dim The dose of regulatory T cells (Tregs) or about 5.0x10 5 to about 3.0x10 9 isolated fresh + CD4 + CD25 + CD127 dim The total dose of regulatory T cells (Tregs), wherein the population consisting of isolated CD45 + has depleted naïve conventional CD3 + CD25 - CD45RA + T cells (Tcon), to contain less than about 5.0x10 5 naïve conventional CD3 + CD25 - CD45RA + T cells (Tcon), less than about 6.0x10 7 total naïve conventional CD3 + CD25 - CD45RA + T cells (Tcon) or less than about 1.0x10 6 total naïve conventional CD3 + CD25 - CD45RA + T cells (Tcon), and wherein the population consisting of isolated CD45 + cells is formulated with an excipient at neutral pH. Other aspects of the disclosure relate to a container comprising: a) about 1.0x10 5 to about 1.0x10 8 CD34 + hematopoietic stem and progenitor cells (HSPCs) or about 5.0x10 5 to about 1.5x10 10 CD34 + total dose of hematopoietic stem and progenitor cells (HSPCs), and one or more excipients; b) about 1.0x10 5 to about 1.0x10 8 CD45RA - memory T cells (Tmem) or about 5.0x10 5 to about 1.5x10 10One CD45RA - The total dose of memory T cells (Tmem), and one or more excipients; and c) approximately 1.0x10 5 per kilogram of body weight of the human subject receiving the product to approximately 2.0x10 7 fresh CD4 + CD25 + CD127 dim regulatory T cells (Treg) or approximately 5.0x10 5 per kilogram of body weight of the human subject receiving the product to approximately 3.0x10 9 isolated fresh + CD4 + CD25 + CD127 dim regulatory T cells (Treg), and one or more excipients, wherein the HSPC, Tmem, and / or Treg have depleted naive conventional CD3 + CD25 - CD45RA + T cells (Tcon), to contain less than approximately 5.0x10 5 naive conventional CD3 + CD25 - CD45RA + T cells (Tcon), less than approximately 6.0x10 7 total naive conventional CD3 + CD25 - CD45RA + T cells (Tcon) or less than approximately 1.0x10 6 total naive conventional CD3 + CD25 - CD45RA + T cells (Tcon). BRIEF DESCRIPTION OF THE DRAWINGS

[0053] 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 present disclosure are utilized, and the accompanying drawings in which:

[0054] Figure 1 A schematic diagram of graft production and administration is shown.

[0055] Figure 2A -C shows neutrophil and platelet engraftment in the study groups.

[0056] Figure 3A - Panel C depicts the incidence of grades 2 - 4 aGVHD in the study cohorts (e.g., MRD / MUD and MMUD in Group A; Haplo in Group B; and no GVHD prophylaxis in Group C).

[0057] Figure 4A - Panel C depicts the incidence of grades 2 - 4 aGVHD in study cohorts that have received more than 1 x 10 6 Tmem per kg of recipient ABW or (adjusted) IBW.

[0058] Figure 5A - Panel C depicts the incidence of grades 3 - 4 aGVHD in different study cohorts.

[0059] Figure 6A - Panel C depicts the incidence of all grades of chronic GVHD in the study cohorts.

[0060] Figure 7A - Panel C depicts the incidence of disease relapse in different study cohorts.

[0061] Figure 8A - Panel C depicts the incidence of NRM in different study cohorts.

[0062] Figure 9A - Panel C depicts the OS in different study cohorts.

[0063] Figure 10A - Panel C depicts the RFS in different study cohorts.

[0064] Figure 11A - Panel C depicts the GRFS in different study cohorts.

[0065] Figure 12A - Panel D depicts the incidence of all infections in each study group at approximately one year post - transplantation.

[0066] Figure 13A - Panel C depicts the incidence of all infections in each study cohort at approximately one year post - transplantation.

[0067] Figure 14A - Panel B depicts the incidence of infections in each study group at approximately 1000 days post - transplantation.

[0068] Figure 15 Compare the incidence of relapse and study design of this study with those of Gooptu (Blood 2021) and Wagner (Blood Advances 2021).

[0069] Figure 16Depicts relapse-free survival without GVHD in haploidentical transplantation.

[0070] Figure 17 Depicts overall survival (OS) achieved by combined Tmem doses.

[0071] Figure 18 Depicts overall survival (OS) achieved by study groups with combined Tmem doses of ≥10x10 6 cells / kg.

[0072] Figure 19 Depicts GVHD-free and relapse-free survival (GRFS) achieved by combined Tmem doses.

[0073] Figure 20 Depicts GVHD-free and relapse-free survival (GRFS) achieved by study groups with combined Tmem doses of ≥10x10 6 cells / kg.

[0074] Figure 21 Depicts relapse-free survival achieved by combined Tmem doses.

[0075] Figure 22 Depicts relapse-free survival achieved by study groups with combined Tmem doses of ≥10x10 6 cells / kg.

[0076] Figure 23 Depicts GVHD-free relapse-free survival (GRFS) in haploidentical transplantation. Detailed Description

[0077] Introduction

[0078] Various embodiments of the present disclosure provide compositions, pharmaceutical treatments, cell populations, solutions, formulations, kits, and / or methods related to improved allogeneic hematopoietic stem cell transplantation (alloHCT).

[0079] Standard alloHSCT is the transplantation of pluripotent hematopoietic stem and progenitor cells (HSPCs) into a recipient, where the HSPCs are typically derived from donor bone marrow, peripheral blood, or umbilical cord blood. The recipient can be given myeloablative conditioning, which kills hematopoietic cells including tumor cells and host immune cells. The HSPCs transplanted into the recipient then reconstitute the hematopoietic compartment. Since donor T cells can exert an anti-tumor effect (referred to as graft-versus-tumor (GVT)), HCT can be used to treat cancer. In patients with chemotherapy-refractory hematologic malignancies, HCT is associated with improved survival.

[0080] Surprisingly, alloHCT recipients receiving a single-agent graft-versus-host disease (GVHD) prophylaxis agent such as tacrolimus have significantly better clinical outcomes than existing alloHCT regimens and standard of care. These recipients have experienced improved clinical outcomes including, for example, increased overall survival, increased relapse-free survival, increased graft-versus-host disease-free 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 relapse, reduced primary graft failure, reduced secondary graft failure, reduced treatment-related mortality, reduced acute and / or chronic GVHD, and shorter time to discharge following receipt of a single-agent GVHD prophylaxis agent consisting of tacrolimus.

[0081] Although alloHCT is associated with improved survival in patients with chemotherapy-refractory hematologic malignancies, some subjects treated with existing alloHCT regimens exhibit cancer relapse, and numerous complications can limit the efficacy of standard alloHCT. The effectiveness of standard alloHCT may be limited by, for example, primary graft failure, secondary graft failure, limited or slow engraftment of various hematopoietic components (e.g., neutrophils, platelets, T cells or B cells), and limited donor chimerism (e.g., T cell chimerism). Additionally, for example, standard alloHCT can result in treatment-related mortality or toxicity, and yet, donor T cells can also attack non-tumor host cells, resulting in graft-versus-host disease (GVHD). GVHD is a major source of post-HCT complications and can be fatal. Management of GVHD may require immunosuppressive therapy or cytotoxic mediation, which can result in toxicity, increased susceptibility to infection, and / or blunting of anti-tumor immunity. The early morbidity and mortality associated with acute graft-versus-host disease (aGVHD; which occurs within the first 100 days after transplantation) are major factors limiting the success of HCT, and the long-term morbidity associated with chronic GVHD (cGVHD) is also a major factor limiting the success of HCT. GVHD is a risk for both HLA-matched transplants and HLA-mismatched transplants. Even when the donor and recipient are HLA-matched, GVHD can occur because the immune system can still recognize other differences between donor tissues.

[0082] Both GVT and GVHD are primarily mediated by conventional T cells, such as naive conventional CD3 + CD25 - CD45RA +Mediated by T cells (Tcon), where the conventional T cells produce an immune response upon recognition of homologous antigens through the T cell receptor. Depleting T cells from hematopoietic stem cell transplantation (HCT) grafts can reduce GVHD, but can also lead to a reduction in GVT and an increased likelihood of cancer recurrence. In addition to Tcon, Treg is another subset of T cells that negatively regulates inflammation and promotes immune tolerance. Treg can prevent or reduce GVHD through its negative regulation of inflammation (including, for example, inflammation triggered by donor Tcon when it recognizes recipient antigens).

[0083] The present disclosure provides compositions and methods for improved alloHCT, including, for example, administering to a subject a cell population comprising CD34+ cells (e.g., HSPC), Treg, and Tmem, and wherein the cell population is depleted of naïve conventional αβ-T cells or naïve conventional CD3 + CD25 - CD45RA + T cells (Tcon). Without wishing to be bound by theory, administering a cell population enriched in Treg and wherein the cell population is depleted of naïve conventional αβ-T cells or naïve conventional CD3 + CD25 - CD45RA + T cells (Tcon) reduces the incidence and / or severity of GVHD and / or enhances GVT. Accordingly, embodiments of the present disclosure provide compositions, pharmaceutical treatments, cell therapy products, cell populations, solutions, formulations, kits, and / or methods for administering an immune cell population to enhance GVT while minimizing GVHD. Thus, the compositions, pharmaceutical treatments, cell therapy products, cell populations, solutions, formulations, kits, and / or methods disclosed herein can maintain the graft-versus-tumor (GVT) effect of an alloHCT administered to a subject suffering from cancer (e.g., hematological cancer) while preventing or reducing graft-versus-host disease (GVHD) in the subject. In some embodiments, one or more doses of the cell population are administered simultaneously or at different times.

[0084] Therapeutic agent for hematopoietic cell transplantation

[0085] Cell population

[0086] Embodiments of the present disclosure provide a pharmaceutical treatment or cell therapy product to be administered to a human subject in need. In some embodiments, the treatment comprises an enriched population consisting of hematopoietic stem / progenitor cells (HSPC), memory T cells (Tmem), regulatory T cells (Treg), and invariant natural killer T cells (iNKT), wherein the cell population is depleted of certain conventional T cells (e.g., naïve conventional αβ-T cells or naïve conventional CD3 + CD25- CD45RA + T cells). In some embodiments, the treatment or therapy may further comprise a solution that does not contain a graft-versus-host disease (GVHD) prophylaxis agent (e.g., tacrolimus) or contains one dose of a GVHD prophylaxis agent. In various embodiments, the HSPC is CD34 + . In some embodiments, the cell therapy product comprises a population consisting of isolated CD45 + cells, wherein the population consisting of isolated CD45 + cells comprises: a) a dose of from about 1.0x10 5 to about 1.0x10 8 CD34 + hematopoietic stem and progenitor cells (HSPCs) or a total dose of from about 5.0x10 5 to about 1.5x10 10 CD34 + hematopoietic stem and progenitor cells (HSPCs) per kilogram of body weight of the human subject receiving the product; b) a dose of from about 1.0x10 5 to about 1.0x10 8 CD45RA - memory T cells (Tmem) or a total dose of from about 5.0x10 5 to about 1.5x10 10 CD45RA - memory T cells (Tmem) per kilogram of body weight of the human subject receiving the product; and c) a dose of from about 1.0x10 5 to about 2.0x10 7 fresh CD4 + CD25 + CD127 dim regulatory T cells (Treg) or a total dose of from about 5.0x10 5 to about 3.0x10 9 isolated fresh + CD4 + CD25 + CD127 dim regulatory T cells (Treg) per kilogram of body weight of the human subject receiving the product, wherein the cell therapy product has depleted naive conventional CD3 + CD25 - CD45RA + T cells (Tcon) to comprise less than about 5.0x10 5 naive conventional CD3 +CD25 - CD45RA + T cells (Tcon), less than about 6.0x10 7 total naive conventional CD3 + CD25 - CD45RA + T cells (Tcon) or less than about 1.0x10 6 total naive conventional CD3 + CD25 - CD45RA + T cells (Tcon), and wherein the population consisting of isolated CD45 + cells is formulated with an excipient at neutral pH.

[0087] In certain embodiments, the present disclosure provides different therapeutic cell populations for forming a pharmaceutical composition or a cell therapy product useful for hematopoietic stem cell / progenitor cell transplantation. The therapeutic cell population can comprise an enriched population consisting of hematopoietic stem cells / progenitor cells (HSPCs), memory T cells (Tmem), regulatory T cells (Tregs), and iNKTs, and wherein the cell population is depleted of naive conventional αβ-T cells and / or depleted of naive conventional CD3 + CD25 - CD45RA + T cells (Tcon).

[0088] In some embodiments, a subject receiving drug therapy has received a myeloablative conditioning regimen comprising thiotepa.

[0089] In some embodiments, different therapeutic cell populations comprising HSPC, Tmem, and Treg are obtained from a single donor. In some embodiments, the cell populations comprising HSPC, Tmem, and Treg are allogeneic with respect to a human subject. In some embodiments, the cell populations comprising HSPC, Tmem, and Treg are obtained from a donor that is HLA-matched with respect to a human subject. In some embodiments, the cell populations comprising HSPC, Tmem, and Treg are obtained from a donor that is HLA-mismatched with respect to a human subject. In some embodiments, the cell populations comprising HSPC, Tmem, and Treg are obtained from a donor that is haploidentical with respect to a human subject. Compositions, pharmaceutical treatments, cell populations, solutions, formulations, kits, and / or methods for improved hematopoietic stem cell transplantation (HCT), such as allogeneic hematopoietic stem cell transplantation (alloHCT), are provided herein. The compositions, pharmaceutical treatments, cell populations, solutions, formulations, kits, and / or methods disclosed herein can comprise cell populations that can be administered in combination with a GVHD prophylactic agent to achieve a positive clinical outcome. The compositions, pharmaceutical treatments, cell populations, solutions, formulations, kits, and / or methods disclosed herein can comprise cell populations that can be administered with or without a GVHD prophylactic agent to achieve a positive clinical outcome. The cell populations can comprise one or more types of cells, such as hematopoietic stem and progenitor cells (HSPC), regulatory T cells (Treg), invariant natural killer T cells (iNKT), memory T cells (Tmem), and combinations thereof. The cell populations can be depleted of naive conventional αβ-T cells and / or depleted of naive conventional CD3 + CD25 - CD45RA + T cells (Tcon).

[0090] The present disclosure provides parameters of cell populations and methods of administering cell populations that can contribute to a successful clinical outcome in HCT recipient subjects. Without wishing to be bound by theory, parameters that can contribute to a successful clinical outcome in HCT recipient subjects include, for example, a conditioning regimen (e.g., a myeloablative conditioning regimen), administration of a GVHD prophylactic agent as described herein (e.g., tacrolimus), the dose of cells administered, the timing of cell administration, the purity criteria of the cells, the method for obtaining the cells, the method for processing or storing the cells, and combinations thereof.

[0091] In some embodiments, CD34 +Hematopoietic stem and progenitor cells (HSPCs) can have extensive self-renewal capacity, as well as the ability to differentiate into specific cell types, e.g., the ability to reconstitute all hematopoietic cell lineages. HSPCs can undergo asynchronous replication, during which two daughter cells with different phenotypes are produced. HSPC cells 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 can be further or alternatively described as CD133 + , CD90 + , CD38 - , CD45RA - , Lin - or any combination thereof. In some embodiments, HSPCs are CD19 - , TCRα / β - or a combination thereof.

[0092] In some embodiments, HSPCs are present in a composition, a cell therapy product, and / or administered to a subject in an amount or dose that can include: from about 1.0x10 5 to about 5.0x10 8 HSPCs per kilogram of the body weight of a human subject, from about 1.0x10 5 to about 1.0x10 8 HSPCs per kilogram of the body weight of a human subject, or from about 5.0x10 5 to about 2.0x10 7 HSPCs per kilogram of the body weight of a human subject. In some embodiments, HSPCs are present in a composition, a cell therapy product, and / or administered to a subject in an amount or dose that includes: about 1.0x10 5 or more HSPCs per kilogram of the body weight of a human subject, about 1.5x10 5 or more HSPCs per kilogram of the body weight of a human subject, about 2.0x10 5 or more HSPCs per kilogram of the body weight of a human subject, about 2.5x10 5 or more HSPCs per kilogram of the body weight of a human subject, about 3.0x10 5 or more HSPCs per kilogram of the body weight of a human subject, about 3.5x10 5 or more HSPCs per kilogram of the body weight of a human subject, about 4.0x10 5 or more HSPCs per kilogram of the body weight of a human subject, about 4.5x10 5 or more HSPCs per kilogram of the body weight of a human subject, about 5.0x105 One or more HSPCs, approximately 5.5x10 per kilogram of the human subject's body weight 5 One or more HSPCs, approximately 6.0x10 per kilogram of the human subject's body weight 5 One or more HSPCs, approximately 6.5x10 per kilogram of the human subject's body weight 5 One or more HSPCs, approximately 7.0x10 per kilogram of the human subject's body weight 5 One or more HSPCs, approximately 7.5x10 per kilogram of the human subject's body weight 5 One or more HSPCs, approximately 8.0x10 per kilogram of the human subject's body weight 5 One or more HSPCs, approximately 8.5x10 per kilogram of the human subject's body weight 5 One or more HSPCs, approximately 9.0x10 per kilogram of the human subject's body weight 5 One or more HSPCs, approximately 9.5x10 per kilogram of the human subject's body weight 5 One or more HSPCs, approximately 1.0x10 per kilogram of the human subject's body weight 6 One or more HSPCs, approximately 1.25x10 per kilogram of the human subject's body weight 6 One or more HSPCs, approximately 1.5x10 per kilogram of the human subject's body weight 6 One or more HSPCs, approximately 1.75x10 per kilogram of the human subject's body weight 6 One or more HSPCs, approximately 2.0x10 per kilogram of the human subject's body weight 6 One or more HSPCs, approximately 2.25x10 per kilogram of the human subject's body weight 6 One or more HSPCs, approximately 2.5x10 per kilogram of the human subject's body weight 6 One or more HSPCs, approximately 2.75x10 per kilogram of the human subject's body weight 6 One or more HSPCs, approximately 3.0x10 per kilogram of the human subject's body weight 6 One or more HSPCs, approximately 3.25x10 per kilogram of the human subject's body weight 6 One or more HSPCs, approximately 3.5x10 per kilogram of the human subject's body weight 6 One or more HSPCs, approximately 3.75x10 per kilogram of the human subject's body weight 6 One or more HSPCs, approximately 4.0x10 per kilogram of the human subject's body weight 6 One or more HSPCs, approximately 4.25x10 per kilogram of the human subject's body weight 6one or more HSPCs, approximately 4.5x10 per kilogram of body weight of a human subject 6 one or more HSPCs, approximately 4.75x10 per kilogram of body weight of a human subject 6 one or more HSPCs, approximately 5.0x10 per kilogram of body weight of a human subject 6 one or more HSPCs, approximately 5.25x10 per kilogram of body weight of a human subject 6 one or more HSPCs, approximately 5.5x10 per kilogram of body weight of a human subject 6 one or more HSPCs, approximately 5.75x10 per kilogram of body weight of a human subject 6 one or more HSPCs, approximately 6.0x10 per kilogram of body weight of a human subject 6 one or more HSPCs, approximately 6.25x10 per kilogram of body weight of a human subject 6 one or more HSPCs, approximately 6.5x10 per kilogram of body weight of a human subject 6 one or more HSPCs, approximately 6.75x10 per kilogram of body weight of a human subject 6 one or more HSPCs, approximately 7.0x10 per kilogram of body weight of a human subject 6 one or more HSPCs, approximately 7.25x10 per kilogram of body weight of a human subject 6 one or more HSPCs, approximately 7.5x10 per kilogram of body weight of a human subject 6 one or more HSPCs, approximately 7.75x10 per kilogram of body weight of a human subject 6 one or more HSPCs, approximately 8.0x10 per kilogram of body weight of a human subject 6 one or more HSPCs, approximately 8.25x10 per kilogram of body weight of a human subject 6 one or more HSPCs, approximately 8.5x10 per kilogram of body weight of a human subject 6 one or more HSPCs, approximately 8.75x10 per kilogram of body weight of a human subject 6 one or more HSPCs, approximately 9.0x10 per kilogram of body weight of a human subject 6 one or more HSPCs, approximately 9.25x10 per kilogram of body weight of a human subject 6 one or more HSPCs, approximately 9.5x10 per kilogram of body weight of a human subject 6 one or more HSPCs, approximately 9.75x10 per kilogram of body weight of a human subject 6 one or more HSPCs, approximately 1.0x10 per kilogram of body weight of a human subject 7One or more HSPCs, approximately 1.25x10 per kilogram of the body weight of a human subject 7 One or more HSPCs, approximately 1.5x10 per kilogram of the body weight of a human subject 7 One or more HSPCs, approximately 1.75x10 per kilogram of the body weight of a human subject 7 One or more HSPCs, approximately 2.0x10 per kilogram of the body weight of a human subject 7 One or more HSPCs, approximately 2.25x10 per kilogram of the body weight of a human subject 7 One or more HSPCs, approximately 2.5x10 per kilogram of the body weight of a human subject 7 One or more HSPCs, approximately 2.75x10 per kilogram of the body weight of a human subject 7 One or more HSPCs, approximately 3.0x10 per kilogram of the body weight of a human subject 7 One or more HSPCs, approximately 3.25x10 per kilogram of the body weight of a human subject 7 One or more HSPCs, approximately 3.5x10 per kilogram of the body weight of a human subject 7 One or more HSPCs, approximately 3.75x10 per kilogram of the body weight of a human subject 7 One or more HSPCs, approximately 4.0x10 per kilogram of the body weight of a human subject 7 One or more HSPCs, approximately 4.25x10 per kilogram of the body weight of a human subject 7 One or more HSPCs, approximately 4.5x10 per kilogram of the body weight of a human subject 7 One or more HSPCs, approximately 4.75x10 per kilogram of the body weight of a human subject 7 One or more HSPCs, approximately 5.0x10 per kilogram of the body weight of a human subject 7 One or more HSPCs, approximately 5.25x10 per kilogram of the body weight of a human subject 7 One or more HSPCs, approximately 5.5x10 per kilogram of the body weight of a human subject 7 One or more HSPCs, approximately 5.75x10 per kilogram of the body weight of a human subject 7 One or more HSPCs, approximately 6.0x10 per kilogram of the body weight of a human subject 7 One or more HSPCs, approximately 6.25x10 per kilogram of the body weight of a human subject 7 One or more HSPCs, approximately 6.5x10 per kilogram of the body weight of a human subject 7 One or more HSPCs, approximately 6.75x10 per kilogram of the body weight of a human subject 7One or more HSPCs, approximately 7.0x10 per kilogram of the human subject's body weight 7 One or more HSPCs, approximately 7.25x10 per kilogram of the human subject's body weight 7 One or more HSPCs, approximately 7.5x10 per kilogram of the human subject's body weight 7 One or more HSPCs, approximately 7.75x10 per kilogram of the human subject's body weight 7 One or more HSPCs, approximately 8.0x10 per kilogram of the human subject's body weight 7 One or more HSPCs, approximately 8.25x10 per kilogram of the human subject's body weight 7 One or more HSPCs, approximately 8.5x10 per kilogram of the human subject's body weight 7 One or more HSPCs, approximately 8.75x10 per kilogram of the human subject's body weight 7 One or more HSPCs, approximately 9.0x10 per kilogram of the human subject's body weight 7 One or more HSPCs, approximately 9.25x10 per kilogram of the human subject's body weight 7 One or more HSPCs, approximately 9.5x10 per kilogram of the human subject's body weight 7 One or more HSPCs, approximately 9.75x10 per kilogram of the human subject's body weight 7 One or more HSPCs, approximately 1.0x10 per kilogram of the human subject's body weight 8 One or more HSPCs, approximately 1.25x10 per kilogram of the human subject's body weight 8 One or more HSPCs, approximately 1.5x10 per kilogram of the human subject's body weight 8 One or more HSPCs, approximately 1.75x10 per kilogram of the human subject's body weight 8 One or more HSPCs, approximately 2.0x10 per kilogram of the human subject's body weight 8 One or more HSPCs, approximately 2.25x10 per kilogram of the human subject's body weight 8 One or more HSPCs, approximately 2.5x10 per kilogram of the human subject's body weight 8 One or more HSPCs, approximately 2.75x10 per kilogram of the human subject's body weight 8 One or more HSPCs, approximately 3.0x10 per kilogram of the human subject's body weight 8 One or more HSPCs, approximately 3.25x10 per kilogram of the human subject's body weight 8 One or more HSPCs, approximately 3.5x10 per kilogram of the human subject's body weight 8One or more HSPCs, about 3.75x10 per kilogram of the body weight of a human subject 8 One or more HSPCs, about 4.0x10 per kilogram of the body weight of a human subject 8 One or more HSPCs, about 4.25x10 per kilogram of the body weight of a human subject 8 One or more HSPCs, about 4.5x10 per kilogram of the body weight of a human subject 8 One or more HSPCs, about 4.75x10 per kilogram of the body weight of a human subject 8 One or more HSPCs or about 5.0x10 per kilogram of the body weight of a human subject 8 One or more HSPCs. 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.

[0093] Such as naive conventional αβ-T cells or naive conventional CD3 + CD25 - CD45RA + Subsets of immune cells such as naive conventional T cells (Tcon), regulatory T cells (Treg), invariant natural killer T cells (iNKT), and memory T cells (Tmem) can contribute to various aspects of GVHD after HCT and can also contribute to, for example, GVT immune responses, immune reconstitution, infection susceptibility, and patient survival.

[0094] Regulatory T cells (“Tregs”) are a specific subset of T cells that negatively regulate (e.g., inhibit) the activation of the immune system and thereby promote immune tolerance. There are multiple subsets of Tregs, such as TCRαβ+CD4+ regulatory T cells, which include natural regulatory T cells (nTregs) and induced regulatory T cells (iTregs). nTregs and iTregs are CD4+CD25+; 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 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, (6) CD3+CD4+CD25+CD127dim 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 certain expression profiles can be achieved based on extracellular markers and does not require cell permeabilization, e.g., selection based on CD4+CD25+CD127dim.

[0095] A cell population 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.

[0096] In some embodiments, the Tregs are CD4+CD25+CD127dim or CD4+FOXP3+. In some embodiments, the Tregs are CD4 + CD25 + CD127 dim and also 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).

[0097] In some embodiments, Tregs are present in a composition, a cell therapy product, and / or administered to a subject in an amount or dose that can include: about 1.0 x 10 5 to about 1.0 x 10 8 Tregs per kilogram of body weight of a human subject, about 1.0 x 10 5 to about 2.0 x 10 7 Tregs per kilogram of body weight of a human subject, about 1.0 x 10 5 to about 1.0 x 10 7 Tregs per kilogram of body weight of a human subject, or about 5.0 x 10 5 to about 4.0 x 10 6 Tregs per kilogram of body weight of a human subject. In some embodiments, Tregs are present in a composition, a cell therapy product, and / or administered to a subject in an amount or dose that includes: about 1.0 x 10 5 or more Tregs per kilogram of body weight of a human subject, about 1.5 x 10 5 or more Tregs per kilogram of body weight of a human subject, about 2.0 x 10 5 or more Tregs per kilogram of body weight of a human subject, about 2.5 x 10 5 or more Tregs per kilogram of body weight of a human subject, about 3.0 x 10 5 or more Tregs per kilogram of body weight of a human subject, about 3.5 x 10 5 or more Tregs per kilogram of body weight of a human subject, about 4.0 x 10 5 or more Tregs per kilogram of body weight of a human subject, about 4.5 x 10 5 or more Tregs per kilogram of body weight of a human subject, about 5.0 x 10 5 or more Tregs per kilogram of body weight of a human subject, about 5.5 x 10 5 or more Tregs per kilogram of body weight of a human subject, about 6.0 x 10 5 or more Tregs per kilogram of body weight of a human subject, about 6.5 x 10 5 or more Tregs per kilogram of body weight of a human subject, about 7.0 x 10 5 or more Tregs per kilogram of body weight of a human subject, about 7.5 x 10 5One or more Tregs, approximately 8.0x10 per kilogram of body weight of a human subject 5 One or more Tregs, approximately 8.5x10 per kilogram of body weight of a human subject 5 One or more Tregs, approximately 9.0x10 per kilogram of body weight of a human subject 5 One or more Tregs, approximately 9.5x10 per kilogram of body weight of a human subject 5 One or more Tregs, approximately 1.0x10 per kilogram of body weight of a human subject 6 One or more Tregs, approximately 1.25x10 per kilogram of body weight of a human subject 6 One or more Tregs, approximately 1.5x10 per kilogram of body weight of a human subject 6 One or more Tregs, approximately 1.75x10 per kilogram of body weight of a human subject 6 One or more Tregs, approximately 2.0x10 per kilogram of body weight of a human subject 6 One or more Tregs, approximately 2.25x10 per kilogram of body weight of a human subject 6 One or more Tregs, approximately 2.5x10 per kilogram of body weight of a human subject 6 One or more Tregs, approximately 2.75x10 per kilogram of body weight of a human subject 6 One or more Tregs, approximately 3.0x10 per kilogram of body weight of a human subject 6 One or more Tregs, approximately 3.25x10 per kilogram of body weight of a human subject 6 One or more Tregs, approximately 3.5x10 per kilogram of body weight of a human subject 6 One or more Tregs, approximately 3.75x10 per kilogram of body weight of a human subject 6 One or more Tregs, approximately 4.0x10 per kilogram of body weight of a human subject 6 One or more Tregs, approximately 4.25x10 per kilogram of body weight of a human subject 6 One or more Tregs, approximately 4.5x10 per kilogram of body weight of a human subject 6 One or more Tregs, approximately 4.75x10 per kilogram of body weight of a human subject 6 One or more Tregs, approximately 5.0x10 per kilogram of body weight of a human subject 6 One or more Tregs, approximately 5.25x10 per kilogram of body weight of a human subject 6 One or more Tregs, approximately 5.5x10 per kilogram of body weight of a human subject 6One or more Tregs, approximately 5.75x10 per kilogram of the body weight of a human subject 6 One or more Tregs, approximately 6.0x10 per kilogram of the body weight of a human subject 6 One or more Tregs, approximately 6.25x10 per kilogram of the body weight of a human subject 6 One or more Tregs, approximately 6.5x10 per kilogram of the body weight of a human subject 6 One or more Tregs, approximately 6.75x10 per kilogram of the body weight of a human subject 6 One or more Tregs, approximately 7.0x10 per kilogram of the body weight of a human subject 6 One or more Tregs, approximately 7.25x10 per kilogram of the body weight of a human subject 6 One or more Tregs, approximately 7.5x10 per kilogram of the body weight of a human subject 6 One or more Tregs, approximately 7.75x10 per kilogram of the body weight of a human subject 6 One or more Tregs, approximately 8.0x10 per kilogram of the body weight of a human subject 6 One or more Tregs, approximately 8.25x10 per kilogram of the body weight of a human subject 6 One or more Tregs, approximately 8.5x10 per kilogram of the body weight of a human subject 6 One or more Tregs, approximately 8.75x10 per kilogram of the body weight of a human subject 6 One or more Tregs, approximately 9.0x10 per kilogram of the body weight of a human subject 6 One or more Tregs, approximately 9.25x10 per kilogram of the body weight of a human subject 6 One or more Tregs, approximately 9.5x10 per kilogram of the body weight of a human subject 6 One or more Tregs, approximately 9.75x10 per kilogram of the body weight of a human subject 6 One or more Tregs, approximately 1.0x10 per kilogram of the body weight of a human subject 7 One or more Tregs, approximately 1.25x10 per kilogram of the body weight of a human subject 7 One or more Tregs, approximately 1.5x10 per kilogram of the body weight of a human subject 7 One or more Tregs, approximately 1.75x10 per kilogram of the body weight of a human subject 7 One or more Tregs, approximately 2.0x10 per kilogram of the body weight of a human subject 7 One or more Tregs, approximately 2.25x10 per kilogram of the body weight of a human subject 7One or more Tregs, approximately 2.5x10 per kilogram of the human subject's body weight 7 One or more Tregs, approximately 2.75x10 per kilogram of the human subject's body weight 7 One or more Tregs, approximately 3.0x10 per kilogram of the human subject's body weight 7 One or more Tregs, approximately 3.25x10 per kilogram of the human subject's body weight 7 One or more Tregs, approximately 3.5x10 per kilogram of the human subject's body weight 7 One or more Tregs, approximately 3.75x10 per kilogram of the human subject's body weight 7 One or more Tregs, approximately 4.0x10 per kilogram of the human subject's body weight 7 One or more Tregs, approximately 4.25x10 per kilogram of the human subject's body weight 7 One or more Tregs, approximately 4.5x10 per kilogram of the human subject's body weight 7 One or more Tregs, approximately 4.75x10 per kilogram of the human subject's body weight 7 One or more Tregs, approximately 5.0x10 per kilogram of the human subject's body weight 7 One or more Tregs, approximately 5.25x10 per kilogram of the human subject's body weight 7 One or more Tregs, approximately 5.5x10 per kilogram of the human subject's body weight 7 One or more Tregs, approximately 5.75x10 per kilogram of the human subject's body weight 7 One or more Tregs, approximately 6.0x10 per kilogram of the human subject's body weight 7 One or more Tregs, approximately 6.25x10 per kilogram of the human subject's body weight 7 One or more Tregs, approximately 6.5x10 per kilogram of the human subject's body weight 7 One or more Tregs, approximately 6.75x10 per kilogram of the human subject's body weight 7 One or more Tregs, approximately 7.0x10 per kilogram of the human subject's body weight 7 One or more Tregs, approximately 7.25x10 per kilogram of the human subject's body weight 7 One or more Tregs, approximately 7.5x10 per kilogram of the human subject's body weight 7 One or more Tregs, approximately 7.75x10 per kilogram of the human subject's body weight 7 One or more Tregs, approximately 8.0x10 per kilogram of the human subject's body weight 7One or more Tregs, approximately 8.25x10 per kilogram of the body weight of a human subject 7 One or more Tregs, approximately 8.5x10 per kilogram of the body weight of a human subject 7 One or more Tregs, approximately 8.75x10 per kilogram of the body weight of a human subject 7 One or more Tregs, approximately 9.0x10 per kilogram of the body weight of a human subject 7 One or more Tregs, approximately 9.25x10 per kilogram of the body weight of a human subject 7 One or more Tregs, approximately 9.5x10 per kilogram of the body weight of a human subject 7 One or more Tregs, approximately 9.75x10 per kilogram of the body weight of a human subject 7 One or more Tregs, approximately 1.0x10 per kilogram of the body weight of a human subject 8 One or more Tregs. 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.

[0098] The cell population of the present disclosure may include memory T cells (Tmem). Tmem may refer to antigen-experienced T cells that express, for example, any one of 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. Tmem provides immunity and is capable of persisting in an inactive state for a long period of time. Tmem is capable of rapidly acquiring effector functions upon re-stimulation with an antigen. The population composed of Tmem may include any combination of T central memory cells and T effector memory cell subsets. In some embodiments, the Tmem of the present disclosure is CD45RA-. In some embodiments, the Tmem of the present disclosure is CD3+CD45RA-CD45RO+. In various methods, the Tmem administered to a subject receiving HCT may, for example, promote GVT, reduce GVHD, reduce susceptibility to cancer recurrence, reduce susceptibility to infection, or a combination thereof.

[0099] In some embodiments, Tmem is present in a composition, a cell therapy product, and / or administered to a subject in an amount or dose that may include: approximately 1.0x10 per kilogram of the body weight of a human subject 5 to approximately 5.0x10 8 Tmem, approximately 1.0x10 per kilogram of the body weight of a human subject 5 to approximately 1.0x10 8about 5.0x10 Tmems per kilogram of human subject body weight 5 to about 2.0x10 7 Tmems. In some embodiments, Tmems are present in a composition, a cell therapy product, and / or administered to a subject in an amount or dose comprising: about 1.0x10 5 or more Tmems per kilogram of human subject body weight, about 1.5x10 5 or more Tmems per kilogram of human subject body weight, about 2.0x10 5 or more Tmems per kilogram of human subject body weight, about 2.5x10 5 or more Tmems per kilogram of human subject body weight, about 3.0x10 5 or more Tmems per kilogram of human subject body weight, about 3.5x10 5 or more Tmems per kilogram of human subject body weight, about 4.0x10 5 or more Tmems per kilogram of human subject body weight, about 4.5x10 5 or more Tmems per kilogram of human subject body weight, about 5.0x10 5 or more Tmems per kilogram of human subject body weight, about 5.5x10 5 or more Tmems per kilogram of human subject body weight, about 6.0x10 5 or more Tmems per kilogram of human subject body weight, about 6.5x10 5 or more Tmems per kilogram of human subject body weight, about 7.0x10 5 or more Tmems per kilogram of human subject body weight, about 7.5x10 5 or more Tmems per kilogram of human subject body weight, about 8.0x10 5 or more Tmems per kilogram of human subject body weight, about 8.5x10 5 or more Tmems per kilogram of human subject body weight, about 9.0x10 5 or more Tmems per kilogram of human subject body weight, about 9.5x10 5 or more Tmems per kilogram of human subject body weight, about 1.0x10 6 or more Tmems per kilogram of human subject body weight, about 1.25x10 6 or more Tmems per kilogram of human subject body weight, about 1.5x10 6one or more Tmems, approximately 1.75x10 per kilogram of body weight of a human subject 6 one or more Tmems, approximately 2.0x10 per kilogram of body weight of a human subject 6 one or more Tmems, approximately 2.25x10 per kilogram of body weight of a human subject 6 one or more Tmems, approximately 2.5x10 per kilogram of body weight of a human subject 6 one or more Tmems, approximately 2.75x10 per kilogram of body weight of a human subject 6 one or more Tmems, approximately 3.0x10 per kilogram of body weight of a human subject 6 one or more Tmems, approximately 3.25x10 per kilogram of body weight of a human subject 6 one or more Tmems, approximately 3.5x10 per kilogram of body weight of a human subject 6 one or more Tmems, approximately 3.75x10 per kilogram of body weight of a human subject 6 one or more Tmems, approximately 4.0x10 per kilogram of body weight of a human subject 6 one or more Tmems, approximately 4.25x10 per kilogram of body weight of a human subject 6 one or more Tmems, approximately 4.5x10 per kilogram of body weight of a human subject 6 one or more Tmems, approximately 4.75x10 per kilogram of body weight of a human subject 6 one or more Tmems, approximately 5.0x10 per kilogram of body weight of a human subject 6 one or more Tmems, approximately 5.25x10 per kilogram of body weight of a human subject 6 one or more Tmems, approximately 5.5x10 per kilogram of body weight of a human subject 6 one or more Tmems, approximately 5.75x10 per kilogram of body weight of a human subject 6 one or more Tmems, approximately 6.0x10 per kilogram of body weight of a human subject 6 one or more Tmems, approximately 6.25x10 per kilogram of body weight of a human subject 6 one or more Tmems, approximately 6.5x10 per kilogram of body weight of a human subject 6 one or more Tmems, approximately 6.75x10 per kilogram of body weight of a human subject 6 one or more Tmems, approximately 7.0x10 per kilogram of body weight of a human subject 6 one or more Tmems, approximately 7.25x10 per kilogram of body weight of a human subject 6one or more Tmem, approximately 7.5x10 per kilogram of body weight of a human subject 6 one or more Tmem, approximately 7.75x10 per kilogram of body weight of a human subject 6 one or more Tmem, approximately 8.0x10 per kilogram of body weight of a human subject 6 one or more Tmem, approximately 8.25x10 per kilogram of body weight of a human subject 6 one or more Tmem, approximately 8.5x10 per kilogram of body weight of a human subject 6 one or more Tmem, approximately 8.75x10 per kilogram of body weight of a human subject 6 one or more Tmem, approximately 9.0x10 per kilogram of body weight of a human subject 6 one or more Tmem, approximately 9.25x10 per kilogram of body weight of a human subject 6 one or more Tmem, approximately 9.5x10 per kilogram of body weight of a human subject 6 one or more Tmem, approximately 9.75x10 per kilogram of body weight of a human subject 6 one or more Tmem, approximately 1.0x10 per kilogram of body weight of a human subject 7 one or more Tmem, approximately 1.25x10 per kilogram of body weight of a human subject 7 one or more Tmem, approximately 1.5x10 per kilogram of body weight of a human subject 7 one or more Tmem, approximately 1.75x10 per kilogram of body weight of a human subject 7 one or more Tmem, approximately 2.0x10 per kilogram of body weight of a human subject 7 one or more Tmem, approximately 2.25x10 per kilogram of body weight of a human subject 7 one or more Tmem, approximately 2.5x10 per kilogram of body weight of a human subject 7 one or more Tmem, approximately 2.75x10 per kilogram of body weight of a human subject 7 one or more Tmem, approximately 3.0x10 per kilogram of body weight of a human subject 7 one or more Tmem, approximately 3.25x10 per kilogram of body weight of a human subject 7 one or more Tmem, approximately 3.5x10 per kilogram of body weight of a human subject 7 one or more Tmem, approximately 3.75x10 per kilogram of body weight of a human subject 7 one or more Tmem, approximately 4.0x10 per kilogram of body weight of a human subject 7One or more Tmem, approximately 4.25x10 per kilogram of body weight of a human subject 7 One or more Tmem, approximately 4.5x10 per kilogram of body weight of a human subject 7 One or more Tmem, approximately 4.75x10 per kilogram of body weight of a human subject 7 One or more Tmem, approximately 5.0x10 per kilogram of body weight of a human subject 7 One or more Tmem, approximately 5.25x10 per kilogram of body weight of a human subject 7 One or more Tmem, approximately 5.5x10 per kilogram of body weight of a human subject 7 One or more Tmem, approximately 5.75x10 per kilogram of body weight of a human subject 7 One or more Tmem, approximately 6.0x10 per kilogram of body weight of a human subject 7 One or more Tmem, approximately 6.25x10 per kilogram of body weight of a human subject 7 One or more Tmem, approximately 6.5x10 per kilogram of body weight of a human subject 7 One or more Tmem, approximately 6.75x10 per kilogram of body weight of a human subject 7 One or more Tmem, approximately 7.0x10 per kilogram of body weight of a human subject 7 One or more Tmem, approximately 7.25x10 per kilogram of body weight of a human subject 7 One or more Tmem, approximately 7.5x10 per kilogram of body weight of a human subject 7 One or more Tmem, approximately 7.75x10 per kilogram of body weight of a human subject 7 One or more Tmem, approximately 8.0x10 per kilogram of body weight of a human subject 7 One or more Tmem, approximately 8.25x10 per kilogram of body weight of a human subject 7 One or more Tmem, approximately 8.5x10 per kilogram of body weight of a human subject 7 One or more Tmem, approximately 8.75x10 per kilogram of body weight of a human subject 7 One or more Tmem, approximately 9.0x10 per kilogram of body weight of a human subject 7 One or more Tmem, approximately 9.25x10 per kilogram of body weight of a human subject 7 One or more Tmem, approximately 9.5x10 per kilogram of body weight of a human subject 7 One or more Tmem, approximately 9.75x10 per kilogram of body weight of a human subject 7one or more Tmems, about 1.0x10 per kilogram of the body weight of a human subject 8 one or more Tmems, about 1.25x10 per kilogram of the body weight of a human subject 8 one or more Tmems, about 1.5x10 per kilogram of the body weight of a human subject 8 one or more Tmems, about 1.75x10 per kilogram of the body weight of a human subject 8 one or more Tmems, about 2.0x10 per kilogram of the body weight of a human subject 8 one or more Tmems, about 2.25x10 per kilogram of the body weight of a human subject 8 one or more Tmems, about 2.5x10 per kilogram of the body weight of a human subject 8 one or more Tmems, about 2.75x10 per kilogram of the body weight of a human subject 8 one or more Tmems, about 3.0x10 per kilogram of the body weight of a human subject 8 one or more Tmems, about 3.25x10 per kilogram of the body weight of a human subject 8 one or more Tmems, about 3.5x10 per kilogram of the body weight of a human subject 8 one or more Tmems, about 3.75x10 per kilogram of the body weight of a human subject 8 one or more Tmems, about 4.0x10 per kilogram of the body weight of a human subject 8 one or more Tmems, about 4.25x10 per kilogram of the body weight of a human subject 8 one or more Tmems, about 4.5x10 per kilogram of the body weight of a human subject 8 one or more Tmems, about 4.75x10 per kilogram of the body weight of a human subject 8 one or more or about 5.0x10 per kilogram of the body weight of a human subject 8 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.

[0100] The cell populations of the present disclosure can include invariant natural killer T cells (iNKT). iNKT are a subset of CD1d-restricted natural killer T (NKT) cells that express a highly conserved αβ-T cell receptor, which in humans includes the Vα24Jα18 TCRα chain (referred to herein as "Vα24Jα18+"). iNKT cells can be identified by binding to CD1d-polymers, such as CD1d-polymers loaded with α-galactosylceramide (GalCer), PBS-57, PBS-44, or other natural or synthetic glycolipids. Another method of identification is an antibody or combination of antibodies that specifically recognizes the Vα24Jα18 region. Examples include Vα24 antibodies, Jα18 antibodies, or monoclonal antibody clone 6B11, which specifically binds to the unique region of the Vα24Jα18 TCR and can be used to identify iNKT cells. iNKT can be CD3+Vα24Jα18+. In some embodiments, the iNKT of the present disclosure is TCRVα24Jα18 + CD127 + .

[0101] 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.

[0102] In some embodiments, iNKT is present in a composition, a cell therapy product, and / or administered to a subject in an amount or dose that can include from about 1 x 10 4 to about 1 x 10 9 iNKT per kilogram of the actual or ideal body weight of a human subject. In some embodiments, iNKT is present in a composition, a cell therapy product, and / or administered to a subject in an amount or dose that can include from about 5.0 × 10 2 to about 2.0 × 10 6 iNKT per kilogram of the body weight of a human subject. In some embodiments, iNKT is present in a composition, a cell therapy product, and / or administered to a subject in an amount or dose that includes: about 5.0x10 2 or more iNKT per kilogram of the body weight of a human subject, about 6.0x10 2 or more iNKT per kilogram of the body weight of a human subject, about 7.0x10 2 or more iNKT per kilogram of the body weight of a human subject, about 8.0x10 2 or more iNKT per kilogram of the body weight of a human subject, about 9.0x102 One or more iNKTs, approximately 1.0x10 per kilogram of the body weight of a human subject 3 One or more iNKTs, approximately 2.0x10 per kilogram of the body weight of a human subject 3 One or more iNKTs, approximately 3.0x10 per kilogram of the body weight of a human subject 3 One or more iNKTs, approximately 4.0x10 per kilogram of the body weight of a human subject 3 One or more iNKTs, approximately 5.0x10 per kilogram of the body weight of a human subject 3 One or more iNKTs, approximately 6.0x10 per kilogram of the body weight of a human subject 3 One or more iNKTs, approximately 7.0x10 per kilogram of the body weight of a human subject 3 One or more iNKTs, approximately 8.0x10 per kilogram of the body weight of a human subject 3 One or more iNKTs, approximately 9.0x10 per kilogram of the body weight of a human subject 3 One or more iNKTs, approximately 1.0x10 per kilogram of the body weight of a human subject 4 One or more iNKTs, approximately 2.0x10 per kilogram of the body weight of a human subject 4 One or more iNKTs, approximately 3.0x10 per kilogram of the body weight of a human subject 4 One or more iNKTs, approximately 4.0x10 per kilogram of the body weight of a human subject 4 One or more iNKTs, approximately 5.0x10 per kilogram of the body weight of a human subject 4 One or more iNKTs, approximately 6.0x10 per kilogram of the body weight of a human subject 4 One or more iNKTs, approximately 7.0x10 per kilogram of the body weight of a human subject 4 One or more iNKTs, approximately 8.0x10 per kilogram of the body weight of a human subject 4 One or more iNKTs, approximately 9.0x10 per kilogram of the body weight of a human subject 4 One or more iNKTs, approximately 1.0x10 per kilogram of the body weight of a human subject 5 One or more iNKTs, approximately 2.0x10 per kilogram of the body weight of a human subject 5 One or more iNKTs, approximately 3.0x10 per kilogram of the body weight of a human subject 5 One or more iNKTs, approximately 4.0x10 per kilogram of the body weight of a human subject 5 One or more iNKTs, approximately 5.0x10 per kilogram of the body weight of a human subject 5One or more iNKTs, about 6.0 x 10 per kilogram of human subject body weight 5 One or more iNKTs, about 7.0 x 10 per kilogram of human subject body weight 5 One or more iNKTs, about 8.0 x 10 per kilogram of human subject body weight 5 One or more iNKTs, about 9.0 x 10 per kilogram of human subject body weight 5 One or more iNKTs, about 1.0 x 10 per kilogram of human subject body weight 6 One or more iNKTs, about 1.5 x 10 per kilogram of human subject body weight 6 One or more iNKTs or about 2.0 x 10 per kilogram of human subject body weight 6 One or more iNKTs.

[0103] As used herein, the term "naive conventional αβ-T cell" or "naive conventional CD3 + CD25 - CD45RA + T cell" refers to one or more non-antigen-experienced T cells that express the phenotypic markers TCRα / β, CD45RA, and express medium to high levels of CD127 (CD127 + ), and do not express or have low expression of CD45RO and CD25. In some embodiments, the naive conventional αβ-T cell or naive conventional CD3 + CD25 - CD45RA + T cell (Tcon) is characterized by the expression of the phenotypic markers of naive conventional αβ-T cells including TCRα, TCRβ, CD3, CD4 or CD8, CD62L, CCR7, CD28, CD127, and CD45RA. In some embodiments, the naive conventional αβ-T cell or naive conventional CD3 + CD25 - CD45RA + T cell (Tcon) is CD3 + CD25 - CD45RA + , and contains polymorphic TCRα and / or polymorphic TCRβ. In some embodiments, the naive conventional αβ-T cell or naive conventional CD3 + CD25 - CD45RA + T cell (Tcon) does not express the Vα24Jα18 TCR found on iNKT cells. In some embodiments, the naive conventional αβ-T cell or naive conventional CD3 + CD25 -CD45RA + T cells (Tcon) are CD45RA+ and are sorted from a cell sample that has been sorted for HSPC, Treg, and Tmem cells.

[0104] In some embodiments, naive conventional αβ-T cells or naive conventional CD3 + CD25 - CD45RA + T cells (Tcon) are CD25 - , CD45RA + or any combination thereof. In some embodiments, naive conventional αβ-T cells or naive conventional CD3 + CD25 - CD45RA + T cells (Tcon) can be TCRα / β + CD45RA + and CD25 - , CD127 + or both. Naive conventional αβ-T cells or naive conventional CD3 + CD25 - CD45RA + T cells (Tcon) can be further characterized as TCRα + TCRβ + CD45RA + CD45RO - CD25 - CD95 - IL-2Rβ - CD127 + Vα24Jα18 - . CD45RA+ naive conventional αβ-T cells or Tcon can be discarded during or after cell sorting for depletion of naive conventional αβ-T cells or naive conventional CD3 + CD25 - CD45RA + T cells (Tcon).

[0105] In some embodiments, naive conventional αβ-T cells or naive conventional CD3 + CD25 - CD45RA + T cells (Tcon) are administered at less than about 5.0 x 10 5 naive conventional CD3 + CD25 - CD45RA +The amount of T cells (Tcon) is present in the composition, cell therapy product, and / or administered to a subject. In some embodiments, naive conventional αβ-T cells or naive conventional CD3 + CD25 - CD45RA + The T cells (Tcon) are present in the composition, cell therapy product, and / or administered to a subject in an amount of less than about 1.0 x 10 5 naive conventional CD3 + CD25 - CD45RA + The amount of T cells (Tcon) is present in the composition, cell therapy product, and / or administered to a subject. In some embodiments, the Tcon is present in the composition, cell therapy product, and / or administered to a subject in the following amounts: less than about 5.0 x 10 5 Tcon per kilogram of the body weight of a human subject, less than about 4.9 x 10 5 Tcon per kilogram of the body weight of a human subject, less than about 4.8 x 10 5 Tcon per kilogram of the body weight of a human subject, less than about 4.7 x 10 5 Tcon per kilogram of the body weight of a human subject, less than about 4.6 x 10 5 Tcon per kilogram of the body weight of a human subject, less than about 4.5 x 10 5 Tcon per kilogram of the body weight of a human subject, less than about 4.4 x 10 5 Tcon per kilogram of the body weight of a human subject, less than about 4.3 x 10 5 Tcon per kilogram of the body weight of a human subject, less than about 4.2 x 10 5 Tcon per kilogram of the body weight of a human subject, less than about 4.1 x 10 5 Tcon per kilogram of the body weight of a human subject, less than about 4.0 x 10 5 Tcon per kilogram of the body weight of a human subject, less than about 3.9 x 10 5 Tcon per kilogram of the body weight of a human subject, less than about 3.8 x 10 5 Tcon per kilogram of the body weight of a human subject, less than about 3.7 x 10 5 Tcon per kilogram of the body weight of a human subject, less than about 3.6 x 10 5 Tcon per kilogram of the body weight of a human subject, less than about 3.5 x 10 5 Tcon per kilogram of the body weight of a human subject, less than about 3.4 x 10 5 Tcon per kilogram of the body weight of a human subject, less than about 3.3 x 10 5Tcons, less than about 3.2x10 per kilogram of human subject body weight 5 Tcons, less than about 3.1x10 per kilogram of human subject body weight 5 Tcons, less than about 3.0x10 per kilogram of human subject body weight 5 Tcons, less than about 2.9x10 per kilogram of human subject body weight 5 Tcons, less than about 2.8x10 per kilogram of human subject body weight 5 Tcons, less than about 2.7x10 per kilogram of human subject body weight 5 Tcons, less than about 2.6x10 per kilogram of human subject body weight 5 Tcons, less than about 2.5x10 per kilogram of human subject body weight 5 Tcons, less than about 2.4x10 per kilogram of human subject body weight 5 Tcons, less than about 2.3x10 per kilogram of human subject body weight 5 Tcons, less than about 2.2x10 per kilogram of human subject body weight 5 Tcons, less than about 2.1x10 per kilogram of human subject body weight 5 Tcons, less than about 2.0x10 per kilogram of human subject body weight 5 Tcons, less than about 1.9x10 per kilogram of human subject body weight 5 Tcons, less than about 1.8x10 per kilogram of human subject body weight 5 Tcons, less than about 1.7x10 per kilogram of human subject body weight 5 Tcons, less than about 1.6x10 per kilogram of human subject body weight 5 Tcons, less than about 1.5x10 per kilogram of human subject body weight 5 Tcons, less than about 1.4x10 per kilogram of human subject body weight 5 Tcons, less than about 1.3x10 per kilogram of human subject body weight 5 Tcons, less than about 1.2x10 per kilogram of human subject body weight 5 Tcons, less than about 1.1x10 per kilogram of human subject body weight 5 Tcons, less than about 1.0x10 per kilogram of human subject body weight 5 Tcons, less than about 9.9x10 per kilogram of human subject body weight 4 Tcons, less than about 9.8x10 per kilogram of human subject body weight 4Tcons, less than approximately 9.7x10 per kilogram of human subject body weight 4 Tcons, less than approximately 9.6x10 per kilogram of human subject body weight 4 Tcons, less than approximately 9.5x10 per kilogram of human subject body weight 4 Tcons, less than approximately 9.4x10 per kilogram of human subject body weight 4 Tcons, less than approximately 9.3x10 per kilogram of human subject body weight 4 Tcons, less than approximately 9.2x10 per kilogram of human subject body weight 4 Tcons, less than approximately 9.1x10 per kilogram of human subject body weight 4 Tcons, less than approximately 9.0x10 per kilogram of human subject body weight 4 Tcons, less than approximately 8.9x10 per kilogram of human subject body weight 4 Tcons, less than approximately 8.8x10 per kilogram of human subject body weight 4 Tcons, less than approximately 8.7x10 per kilogram of human subject body weight 4 Tcons, less than approximately 8.6x10 per kilogram of human subject body weight 4 Tcons, less than approximately 8.5x10 per kilogram of human subject body weight 4 Tcons, less than approximately 8.4x10 per kilogram of human subject body weight 4 Tcons, less than approximately 8.3x10 per kilogram of human subject body weight 4 Tcons, less than approximately 8.2x10 per kilogram of human subject body weight 4 Tcons, less than approximately 8.1x10 per kilogram of human subject body weight 4 Tcons, less than approximately 8.0x10 per kilogram of human subject body weight 4 Tcons, less than approximately 7.9x10 per kilogram of human subject body weight 4 Tcons, less than approximately 7.8x10 per kilogram of human subject body weight 4 Tcons, less than approximately 7.7x10 per kilogram of human subject body weight 4 Tcons, less than approximately 7.6x10 per kilogram of human subject body weight 4 Tcons, less than approximately 7.5x10 per kilogram of human subject body weight 4 Tcons, less than approximately 7.4x10 per kilogram of human subject body weight 4 Tcons, less than approximately 7.3x10 per kilogram of human subject body weight 4Tcons, less than approximately 7.2x10 per kilogram of human subject body weight 4 Tcons, less than approximately 7.1x10 per kilogram of human subject body weight 4 Tcons, less than approximately 7.0x10 per kilogram of human subject body weight 4 Tcons, less than approximately 6.9x10 per kilogram of human subject body weight 4 Tcons, less than approximately 6.8x10 per kilogram of human subject body weight 4 Tcons, less than approximately 6.7x10 per kilogram of human subject body weight 4 Tcons, less than approximately 6.6x10 per kilogram of human subject body weight 4 Tcons, less than approximately 6.5x10 per kilogram of human subject body weight 4 Tcons, less than approximately 6.4x10 per kilogram of human subject body weight 4 Tcons, less than approximately 6.3x10 per kilogram of human subject body weight 4 Tcons, less than approximately 6.2x10 per kilogram of human subject body weight 4 Tcons, less than approximately 6.1x10 per kilogram of human subject body weight 4 Tcons, less than approximately 6.0x10 per kilogram of human subject body weight 4 Tcons, less than approximately 5.9x10 per kilogram of human subject body weight 4 Tcons, less than approximately 5.8x10 per kilogram of human subject body weight 4 Tcons, less than approximately 5.7x10 per kilogram of human subject body weight 4 Tcons, less than approximately 5.6x10 per kilogram of human subject body weight 4 Tcons, less than approximately 5.5x10 per kilogram of human subject body weight 4 Tcons, less than approximately 5.4x10 per kilogram of human subject body weight 4 Tcons, less than approximately 5.3x10 per kilogram of human subject body weight 4 Tcons, less than approximately 5.2x10 per kilogram of human subject body weight 4 Tcons, less than approximately 5.1x10 per kilogram of human subject body weight 4 Tcons, less than approximately 5.0x10 per kilogram of human subject body weight 4 Tcons, less than approximately 4.9x10 per kilogram of human subject body weight 4 Tcons, less than approximately 4.8x10 per kilogram of human subject body weight 4Tcons, less than about 4.7x10 per kilogram of human subject body weight 4 Tcons, less than about 4.6x10 per kilogram of human subject body weight 4 Tcons, less than about 4.5x10 per kilogram of human subject body weight 4 Tcons, less than about 4.4x10 per kilogram of human subject body weight 4 Tcons, less than about 4.3x10 per kilogram of human subject body weight 4 Tcons, less than about 4.2x10 per kilogram of human subject body weight 4 Tcons, less than about 4.1x10 per kilogram of human subject body weight 4 Tcons, less than about 4.0x10 per kilogram of human subject body weight 4 Tcons, less than about 3.9x10 per kilogram of human subject body weight 4 Tcons, less than about 3.8x10 per kilogram of human subject body weight 4 Tcons, less than about 3.7x10 per kilogram of human subject body weight 4 Tcons, less than about 3.6x10 per kilogram of human subject body weight 4 Tcons, less than about 3.5x10 per kilogram of human subject body weight 4 Tcons, less than about 3.4x10 per kilogram of human subject body weight 4 Tcons, less than about 3.3x10 per kilogram of human subject body weight 4 Tcons, less than about 3.2x10 per kilogram of human subject body weight 4 Tcons, less than about 3.1x10 per kilogram of human subject body weight 4 Tcons, less than about 3.0x10 per kilogram of human subject body weight 4 Tcons, less than about 2.9x10 per kilogram of human subject body weight 4 Tcons, less than about 2.8x10 per kilogram of human subject body weight 4 Tcons, less than about 2.7x10 per kilogram of human subject body weight 4 Tcons, less than about 2.6x10 per kilogram of human subject body weight 4 Tcons, less than about 2.5x10 per kilogram of human subject body weight 4 Tcons, less than about 2.4x10 per kilogram of human subject body weight 4 Tcons, less than about 2.3x10 per kilogram of human subject body weight 4Tcons, less than approximately 2.2x10 per kilogram of human subject body weight 4 Tcons, less than approximately 2.1x10 per kilogram of human subject body weight 4 Tcons, less than approximately 2.0x10 per kilogram of human subject body weight 4 Tcons, less than approximately 1.9x10 per kilogram of human subject body weight 4 Tcons, less than approximately 1.8x10 per kilogram of human subject body weight 4 Tcons, less than approximately 1.7x10 per kilogram of human subject body weight 4 Tcons, less than approximately 1.6x10 per kilogram of human subject body weight 4 Tcons, less than approximately 1.5x10 per kilogram of human subject body weight 4 Tcons, less than approximately 1.4x10 per kilogram of human subject body weight 4 Tcons, less than approximately 1.3x10 per kilogram of human subject body weight 4 Tcons, less than approximately 1.2x10 per kilogram of human subject body weight 4 Tcons, less than approximately 1.1x10 per kilogram of human subject body weight 4 Tcons, less than approximately 1.0x10 per kilogram of human subject body weight 4 Tcons, less than approximately 9.9x10 per kilogram of human subject body weight 3 Tcons, less than approximately 9.8x10 per kilogram of human subject body weight 3 Tcons, less than approximately 9.7x10 per kilogram of human subject body weight 3 Tcons, less than approximately 9.6x10 per kilogram of human subject body weight 3 Tcons, less than approximately 9.5x10 per kilogram of human subject body weight 3 Tcons, less than approximately 9.4x10 per kilogram of human subject body weight 3 Tcons, less than approximately 9.3x10 per kilogram of human subject body weight 3 Tcons, less than approximately 9.2x10 per kilogram of human subject body weight 3 Tcons, less than approximately 9.1x10 per kilogram of human subject body weight 3 Tcons, less than approximately 9.0x10 per kilogram of human subject body weight 3 Tcons, less than approximately 8.9x10 per kilogram of human subject body weight 3 Tcons, less than approximately 8.8x10 per kilogram of human subject body weight 3Tcons, less than approximately 8.7x10 per kilogram of human subject weight 3 Tcons, less than approximately 8.6x10 per kilogram of human subject weight 3 Tcons, less than approximately 8.5x10 per kilogram of human subject weight 3 Tcons, less than approximately 8.4x10 per kilogram of human subject weight 3 Tcons, less than approximately 8.3x10 per kilogram of human subject weight 3 Tcons, less than approximately 8.2x10 per kilogram of human subject weight 3 Tcons, less than approximately 8.1x10 per kilogram of human subject weight 3 Tcons, less than approximately 8.0x10 per kilogram of human subject weight 3 Tcons, less than approximately 7.9x10 per kilogram of human subject weight 3 Tcons, less than approximately 7.8x10 per kilogram of human subject weight 3 Tcons, less than approximately 7.7x10 per kilogram of human subject weight 3 Tcons, less than approximately 7.6x10 per kilogram of human subject weight 3 Tcons, less than approximately 7.5x10 per kilogram of human subject weight 3 Tcons, less than approximately 7.4x10 per kilogram of human subject weight 3 Tcons, less than approximately 7.3x10 per kilogram of human subject weight 3 Tcons, less than approximately 7.2x10 per kilogram of human subject weight 3 Tcons, less than approximately 7.1x10 per kilogram of human subject weight 3 Tcons, less than approximately 7.0x10 per kilogram of human subject weight 3 Tcons, less than approximately 6.9x10 per kilogram of human subject weight 3 Tcons, less than approximately 6.8x10 per kilogram of human subject weight 3 Tcons, less than approximately 6.7x10 per kilogram of human subject weight 3 Tcons, less than approximately 6.6x10 per kilogram of human subject weight 3 Tcons, less than approximately 6.5x10 per kilogram of human subject weight 3 Tcons, less than approximately 6.4x10 per kilogram of human subject weight 3 Tcons, less than approximately 6.3x10 per kilogram of human subject weight 3Tcons, less than about 6.2x10 per kilogram of human subject weight 3 Tcons, less than about 6.1x10 per kilogram of human subject weight 3 Tcons, less than about 6.0x10 per kilogram of human subject weight 3 Tcons, less than about 5.9x10 per kilogram of human subject weight 3 Tcons, less than about 5.8x10 per kilogram of human subject weight 3 Tcons, less than about 5.7x10 per kilogram of human subject weight 3 Tcons, less than about 5.6x10 per kilogram of human subject weight 3 Tcons, less than about 5.5x10 per kilogram of human subject weight 3 Tcons, less than about 5.4x10 per kilogram of human subject weight 3 Tcons, less than about 5.3x10 per kilogram of human subject weight 3 Tcons, less than about 5.2x10 per kilogram of human subject weight 3 Tcons, less than about 5.1x10 per kilogram of human subject weight 3 Tcons, less than about 5.0x10 per kilogram of human subject weight 3 Tcons, less than about 4.9x10 per kilogram of human subject weight 3 Tcons, less than about 4.8x10 per kilogram of human subject weight 3 Tcons, less than about 4.7x10 per kilogram of human subject weight 3 Tcons, less than about 4.6x10 per kilogram of human subject weight 3 Tcons, less than about 4.5x10 per kilogram of human subject weight 3 Tcons, less than about 4.4x10 per kilogram of human subject weight 3 Tcons, less than about 4.3x10 per kilogram of human subject weight 3 Tcons, less than about 4.2x10 per kilogram of human subject weight 3 Tcons, less than about 4.1x10 per kilogram of human subject weight 3 Tcons, less than about 4.0x10 per kilogram of human subject weight 3 Tcons, less than about 3.9x10 per kilogram of human subject weight 3 Tcons, less than about 3.8x10 per kilogram of human subject weight 3Tcons, less than approximately 3.7x10 per kilogram of human subject body weight 3 Tcons, less than approximately 3.6x10 per kilogram of human subject body weight 3 Tcons, less than approximately 3.5x10 per kilogram of human subject body weight 3 Tcons, less than approximately 3.4x10 per kilogram of human subject body weight 3 Tcons, less than approximately 3.3x10 per kilogram of human subject body weight 3 Tcons, less than approximately 3.2x10 per kilogram of human subject body weight 3 Tcons, less than approximately 3.1x10 per kilogram of human subject body weight 3 Tcons, less than approximately 3.0x10 per kilogram of human subject body weight 3 Tcons, less than approximately 2.9x10 per kilogram of human subject body weight 3 Tcons, less than approximately 2.8x10 per kilogram of human subject body weight 3 Tcons, less than approximately 2.7x10 per kilogram of human subject body weight 3 Tcons, less than approximately 2.6x10 per kilogram of human subject body weight 3 Tcons, less than approximately 2.5x10 per kilogram of human subject body weight 3 Tcons, less than approximately 2.4x10 per kilogram of human subject body weight 3 Tcons, less than approximately 2.3x10 per kilogram of human subject body weight 3 Tcons, less than approximately 2.2x10 per kilogram of human subject body weight 3 Tcons, less than approximately 2.1x10 per kilogram of human subject body weight 3 Tcons, less than approximately 2.0x10 per kilogram of human subject body weight 3 Tcons, less than approximately 1.9x10 per kilogram of human subject body weight 3 Tcons, less than approximately 1.8x10 per kilogram of human subject body weight 3 Tcons, less than approximately 1.7x10 per kilogram of human subject body weight 3 Tcons, less than approximately 1.6x10 per kilogram of human subject body weight 3 Tcons, less than approximately 1.5x10 per kilogram of human subject body weight 3 Tcons, less than approximately 1.4x10 per kilogram of human subject body weight 3 Tcons, less than approximately 1.3x10 per kilogram of human subject body weight 3less than about 1.2 x 10 Tcons per kilogram of human subject body weight 3 less than about 1.1 x 10 Tcons per kilogram of human subject body weight 3 less than about 1.0 x 10 Tcons per kilogram of human subject body weight 3 Tcons.

[0106] In some embodiments, the cell populations of the present disclosure, such as populations composed of isolated CD45 + cells, can comprise one or more cells that contain one or more chimeric receptors. In some embodiments, the one or more cells can 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 can be targeted. In some embodiments, the chimeric receptor is a chimeric antigen receptor or a T cell receptor.

[0107] Without wishing to be bound by theory, the cell populations of the present disclosure contain CD34 + cells (i.e., HSPCs), and are enriched in Tregs and Tmems, which contribute to positive clinical outcomes, such as, by reducing the incidence and / or severity of GVHD in transplant recipient subjects, and / or improving immune reconstitution in transplant recipients, and / or reducing the infection rate. Administering a cell population comprising HSPCs enriched in Tregs and Tmems can promote retention of the 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, for example, relative to alternative hematopoietic stem cell transplantation (HCT) methods, such as standard myeloablative allogeneic hematopoietic stem cell transplantation (alloHSCT), i.e., methods different from the compositions, pharmaceutical treatments, cell populations, solutions, formulations, kits, and / or methods disclosed herein, administering cells enriched in Tregs and / or Tmems, and / or depleting naïve conventional αβ-T cells or naïve conventional CD3 + CD25 - CD45RA + T cells (Tcons) can prevent GVHD, and / or can promote GVT effects. In some embodiments, relative to alternative HCT methods, such as standard myeloablative allogeneic hematopoietic stem cell transplantation (alloHSCT), i.e., methods different from the compositions, pharmaceutical treatments, cell populations, solutions, formulations, kits, and / or methods disclosed herein, administering cells enriched in Tregs and / or Tmems, and / or depleting naïve conventional αβ-T cells or naïve conventional CD3 +CD25 - CD45RA + A cell population of T cells (Tcon) promotes the GVT effect.

[0108] 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 of a cell population comprising HSPC (e.g., a cell population comprising Treg) and a prophylactic agent. In some embodiments, compared to the compositions or treatment regimens of the present disclosure, the alternative composition or treatment regimen comprises additional cell populations or agents, such as additional or different GVHD prophylactic agents.

[0109] Collection, processing, and preparation of cells

[0110] 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.

[0111] In some embodiments, a biological sample (e.g., a peripheral blood donation, umbilical cord blood donation, or bone marrow donation) can be 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 sorted to isolate one or more cell populations of interest, such as one or more populations composed of HSPC, one or more populations composed of Treg, one or more populations composed of Tmem, one or more populations composed of iNKT, or any combination thereof. In some cases, the biological sample of the present disclosure can be contacted with a molecule that specifically binds to CD34 to isolate HSPC. The sample can be enriched for CD34 + cells to produce CD34 + cell populations and CD34 - cell populations. In some cases, the CD34 - cell population can be contacted with a molecule that specifically binds to CD25 and / or a molecule that specifically binds to 6B11. For the CD25 + cell population, the sample can then be enriched for CD25 - of the sample by sorting the CD34 + and / or 6B11 + cells, thereby producing a CD34 - CD25 - cell population or a CD34 - CD25 - 6B11 - cell population, as well as a CD34 - CD25 + cell population or a CD34 - CD25 + 6B11+ Cell populations. CD34 can be further sorted - CD25 + 6B11 + Cell populations to generate Treg and iNKT cell populations. CD34 - CD25 + Cells or CD34 - CD25 + 6B11 + Cells can be contacted with a molecule that specifically binds to CD4 and a molecule that specifically binds to CD127. The cells can then be sorted to generate CD34 - CD25 + CD4 + CD127 dim / - Treg cell population or CD34 - CD25 + 6B11 + CD4 + CD127 dim / - Treg cell population. In some cases, CD34 can be further sorted - CD25 - Cell population or CD34 - CD25 - 6B11 - Cell population to enrich for Tmem cells. The cells can be contacted with a molecule that specifically binds to CD45RA. The cell sample can be sorted to generate CD34 - CD25 - CD45RA - Tmem cell population or CD34 - CD25 - 6B11 - CD45RA - Tmem cell population. CD45RA + Naive conventional αβ-T cells or naive conventional CD3 + CD25 - CD45RA + T cells (Tcon) can be discarded for depletion of naive conventional αβ-T cells or naive conventional CD3 + CD25 - CD45RA + T cells (Tcon), i.e., depletion of Tcon.

[0112] 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, at most two mobilized peripheral blood donations are collected from a donor. In some embodiments, the mobilized peripheral blood donation is a HSPC-mobilized peripheral blood apheresis donation. In some embodiments, prior to the peripheral blood donation, the donor can be inoculated with a tumor antigen and / or a pathogen to enhance the graft's anti-infection ability.

[0113] 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 population of the present disclosure is obtained from a bone marrow donation. In some embodiments, at least one cord blood donation is collected from a donor (e.g., an HLA-matched or HLA-mismatched allogeneic donor). In some embodiments, the cell population of the present disclosure is obtained from a cord blood donation.

[0114] In an embodiment, at least one of the mobilized peripheral blood donations, at least one of the bone marrow donations, or at least one of the cord blood donations is processed and sorted to enrich for CD34+ cells, Tregs, and / or Tmem. CD34 + Cell, Treg, and Tcon processing and sorting can 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 cord blood donations can be processed and sorted to first enrich for CD34 + cells, then enrich for Tregs, and then enrich for Tmem. Alternatively, at least one of the mobilized peripheral blood donations, at least one of the bone marrow donations, or at least one of the cord blood donations can be processed and sorted to first enrich for CD34 + cells, then enrich for Tmem, and then enrich for Tregs. Alternatively, at least one of the mobilized peripheral blood donations, at least one of the bone marrow donations, or at least one of the cord blood donations can be processed and sorted to first enrich for Tregs, then enrich for CD34 + cells, and then enrich for Tmem. Alternatively, at least one of the mobilized peripheral blood donations, at least one of the bone marrow donations, or at least one of the cord blood donations can be processed and sorted to first enrich for Tregs, then enrich for Tmem, and then enrich for CD34 + 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 cord blood donations can be processed and sorted to first enrich for Tmem, then enrich for CD34 +Cells and then enrich Tregs. Alternatively, at least one of a mobilized peripheral blood donation, at least one of a bone marrow donation, or at least one of a cord blood donation can be processed and sorted to first enrich Tmem, then enrich Tregs, and then enrich CD34 + cells.

[0115] In some embodiments, the processing and sorting time of at least one of a mobilized peripheral blood donation, at least one of a bone marrow donation, or at least one of a cord blood donation is less than about 40 hours, the processing and sorting time of at least one of a mobilized peripheral blood donation, at least one of a bone marrow donation, or at least one of a cord blood donation is less than about 35 hours, the processing and sorting time of at least one of a mobilized peripheral blood donation, at least one of a bone marrow donation, or at least one of a cord blood donation is less than about 30 hours, the processing and sorting time of at least one of a mobilized peripheral blood donation, at least one of a bone marrow donation, or at least one of a cord blood donation is less than about 25 hours, the processing and sorting time of at least one of a mobilized peripheral blood donation, at least one of a bone marrow donation, or at least one of a cord blood donation is less than about 20 hours, the processing and sorting time of at least one of a mobilized peripheral blood donation, at least one of a bone marrow donation, or at least one of a cord blood donation is less than about 15 hours.

[0116] In some embodiments, the processing and sorting time of at least one of a mobilized peripheral blood donation, at least one of a bone marrow donation, or at least one of a cord blood donation is at most about 35 hours, the processing and sorting time of at least one of a mobilized peripheral blood donation, at least one of a bone marrow donation, or at least one of a cord blood donation is at most about 30 hours, the processing and sorting time of at least one of a mobilized peripheral blood donation, at least one of a bone marrow donation, or at least one of a cord blood donation is at most about 25 hours, the processing and sorting time of at least one of a mobilized peripheral blood donation, at least one of a bone marrow donation, or at least one of a cord blood donation is at most about 20 hours, the processing and sorting time of at least one of a mobilized peripheral blood donation, at least one of a bone marrow donation, or at least one of a cord blood donation is at most about 15 hours.

[0117] In some embodiments, the cell population of the present disclosure (e.g., isolated from CD45 +The cell population (population of cells) is obtained from whole blood. The cell populations of the present disclosure can be obtained from apheresis products, such as mobilized apheresis products, such as those mobilized by administering to a donor one or more mobilizing agents. 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), plerixafor, CXCR2 ligands (e.g., GROβ), sphingosine-1-phosphate (S1P) agonists (e.g., SEW2871), VCAM / VLA-4 inhibitors (e.g., BIO5192), proteasome inhibitors (e.g., Bortezomib), parathyroid hormone, hypoxia-inducible factor (HIF) stabilizers (e.g., FG-4497), and combinations thereof. Techniques for mobilizing stem cells into the peripheral blood can include administering to the donor a mobilizing agent at, for example, 10 μg / kg / day to 40 μg / kg / day. The mobilizing 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 at about, for example, 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 a dose of the mobilizing agent.

[0118] 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 apheresis products. 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 apheresis products from one donor and apheresis products from at least a second donor. In some embodiments, the cell populations of the present disclosure can be obtained from more than one apheresis product, the more than one apheresis product being obtained from donors on different days. In some embodiments, a bone marrow stimulant (e.g., 0.24 mg / kg of plerixafor subcutaneously) can be administered to the donor after the first apheresis and before subsequent aphereses.

[0119] The cell populations of the present disclosure can be refined by selection from a population consisting of cells (e.g., peripheral blood or apheresis products, bone marrow, or cord blood). The method of selecting the cell population may include methods involving positive or negative selection of the relevant cell population. The method of selecting the cell population can include affinity reagents, including but not limited to antibodies, full-length antibodies, antibody fragments, naturally occurring antibodies, synthetic antibodies, engineered antibodies, full-length affilin antibodies, affilin antibody fragments, full-length anticalin, anticalin fragments, full-length avimers, avimer fragments, full-length DARPins, DARPin fragments, full-length fynom ers, fynomer fragments, full-length Kunitz domain peptides, Kunitz domain peptide fragments, full-length monobody antibodies, monobody antibody fragments, peptides, or polyamino acids. In some embodiments, the affinity reagent is directly conjugated to a detection reagent and / or a 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 the purification reagent are fluorescent reagents, magnetic reagents, etc. In some cases, the detection reagent and / or the purification reagent are magnetic particles for column purification. For example, magnetic column purification can be performed using a Miltenyi system (CliniMACs) of columns, antibodies, buffers, preparation materials, and reagents.

[0120] The affinity reagent can include an immunoaffinity reagent that uses the binding specificity of an antibody or its fragment or derivative for positive or negative selection of the cell population of interest. The method of selecting the cell population can include an affinity agent and a column, e.g., magnetic-activated cell sorting (MACS) using a specific antibody and beads. The method of selecting the cell population can include fluorescence-activated cell sorting (FACS), in which the cell population is sorted based on a staining profile using one or more fluorescently conjugated antibodies. The method of selecting the cell population can include physical adsorption, e.g., physical adsorption of T cells to a protein ligand such as lectin.

[0121] The number of cells in the various cell populations provided herein can be determined, for example, by quantifying cell determinants by flow cytometry. In some embodiments, the dose calculation is adjusted based on the measurement results of cell viability measurements, e.g., viability determined by flow cytometry using propidium iodide or 7-AAD or by trypan blue exclusion.

[0122] In various embodiments, one or more immunoseparation particles (ISPs) are used to process and sort at least one mobilized peripheral blood donation, at least one bone marrow donation, and / or at least one umbilical cord blood donation. For example, the ISP comprises an affinity reagent such as an immunomagnetic separation particle, which may be an antibody conjugated to an iron-containing particle respectively. In some embodiments, the affinity reagent comprises a plurality of CD34 reagents (e.g., anti-CD34 antibodies) that bind to one or more CD34 receptors on HSPCs.

[0123] In some cases, at least a portion of the plurality of ISPs are linked to CD34+ receptors on HSPCs of the HSPC cell population; 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 from about 1000 to about 20,000.

[0124] In some embodiments, the average number of ISPs per HSPC in the HSPC cell population can be from about 1,500 to about 20,000. In some embodiments, the average number of ISPs per HSPC in the HSPC cell population can be at least about 1,500. In some embodiments, the average number of ISPs per HSPC in the HSPC cell population can be at most about 20,000. In some embodiments, the average number of ISPs per HSPC in the HSPC cell population can be from about 1,500 to about 2,000, from about 1,500 to about 5,000, from about 1,500 to about 6,000, from about 1,500 to about 10,000, from about 1,500 to about 12,000, from about 1,500 to about 15,000, from about 1,500 to about 20,000, from about 2,000 to about 5,000, from about 2,000 to about 6,000, from about 2,000 to about 10,000, from about 2,000 to about 12,000, from about 2,000 to about 15,000, from about 2,000 to about 20,000, from about 5,000 to about 6,000, from about 5,000 to about 10,000, from about 5,000 to about 12,000, from about 5,000 to about 15,000, from about 5,000 to about 20,000, from about 6,000 to about 10,000, from about 6,000 to about 12,000, from about 6,000 to about 15,000, from about 6,000 to about 20,000, from about 10,000 to about 12,000, from about 10,000 to about 15,000, from about 10,000 to about 20,000, from about 12,000 to about 15,000, from about 12,000 to about 20,000, or from about 15,000 to about 20,000. In some embodiments, the average number of ISPs per HSPC in the HSPC cell population can 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 can 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 can be at most 1,500, 2,000, 5,000, 6,000, 10,000, 12,000, 15,000, or 20,000.

[0125] In some cases, at least a portion of the plurality of ISPs are linked to CD25+ receptors on the cells of the Treg cell population; 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 from about 1500 to about 2500. In some cases, at least a portion of the plurality of ISPs are linked to CD3+ receptors on the cells of a heterologous cell population; optionally, the average number of ISPs per cell in the T heterologous population is less than about 4,000.

[0126] In some embodiments, the average number of ISPs per Treg cell in the Treg cell population can be from about 500 to about 4,000. In some embodiments, the average number of ISPs per Treg cell in the Treg cell population can be at least about 500. In some embodiments, the average number of ISPs per Treg cell in the Treg cell population can be at most about 4,000. In some embodiments, the average number of ISPs per Treg cell in the Treg cell population can be from about 500 to about 1,000, from about 500 to about 1,500, from about 500 to about 2,000, from about 500 to about 2,500, from about 500 to about 3,000, from about 500 to about 4,000, from about 1,000 to about 1,500, from about 1,000 to about 2,000, from about 1,000 to about 2,500, from about 1,000 to about 3,000, from about 1,000 to about 4,000, from about 1,500 to about 2,000, from about 1,500 to about 2,500, from about 1,500 to about 3,000, from about 1,500 to about 4,000, from about 2,000 to about 2,500, from about 2,000 to about 3,000, from about 2,000 to about 4,000, from about 2,500 to about 3,000, from about 2,500 to about 4,000, or from about 3,000 to about 4,000. In some embodiments, the average number of ISPs per Treg cell in the Treg cell population can be about 500, about 1,000, about 1,500, about 2,000, about 2,500, about 3,000, or about 4,000. In some embodiments, the average number of ISPs per Treg cell in the Treg cell population can 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 can be at most 500, 1,000, 1,500, 2,000, 2,500, 3,000, or 4,000.

[0127] The cell populations of the present disclosure can be enriched for Tregs. Tregs can be selected based on the expression of markers including CD3, CD4, CD25, CD127, FOXP3, and combinations thereof. Tregs can be isolated from whole blood. Tregs can be isolated from apheresis products, bone marrow, and / or umbilical cord blood. Tregs can be isolated from cell populations that have been pre-enriched and / or depleted of one or more other cell types, e.g., from a cell population depleted of CD34+ cells. In some embodiments, Tregs are isolated from the flow-through fraction selected by CD34+ MACS. The number of Tregs in the cell population can be determined, e.g., by flow cytometry, where Tregs can be identified as, e.g., CD4+CD25+CD127dim or CD4+FOXP3+. Dose calculations can be adjusted based on the results of cell viability measurements, e.g., viability determined by flow cytometry using propidium iodide or 7-AAD or by trypan blue exclusion.

[0128] The cell populations of the present disclosure can comprise a population consisting of Tmem. The population consisting of Tmem can be derived from peripheral blood, bone marrow, and / or umbilical cord blood. The population consisting of Tmem can be derived from apheresis products. The cell population can be enriched for Tmem, e.g., by sorting based on the expression of various markers using MACS, FACS, or a combination thereof. For example, the population consisting of Tmem can be enriched by sorting CD3+CD45RA-CD45RO+ cells. The number of Tmem present in the population can be quantified, e.g., by quantifying CD3+CD45RA-CD45RO+ cells by means of flow cytometry. The number of CD3+CD45RA-CD45RO+ cells in an aliquot and the volume containing an appropriate dose of Tmem to be administered to a recipient can be determined. Dose calculations can be adjusted based on the results of cell viability measurements, e.g., viability determined by flow cytometry using propidium iodide or 7-AAD or by trypan blue exclusion.

[0129] The cell populations of the present disclosure can comprise a population consisting of iNKT. The population consisting of iNKT can be derived from peripheral blood, bone marrow, and / or umbilical cord blood. The population consisting of iNKT can be derived from apheresis products. The cell populations can be enriched for iNKT, e.g., by sorting based on the expression of various markers using MACS, FACS, or a combination thereof. For example, the population consisting of iNKT can be enriched by sorting CD3+Vα24Jα18+ cells. The number of iNKT present in the population can be quantified, e.g., by quantifying CD3+Vα24Jα18+ cells by means of flow cytometry. The number of CD3+Vα24Jα18+ cells in an aliquot and the volume containing an appropriate dose of iNKT to be administered to a recipient can be determined. In some embodiments, the dose calculation is adjusted based on the measurement results of cell viability measurements, e.g., viability determined by flow cytometry using propidium iodide or 7-AAD or by trypan blue exclusion.

[0130] The cell populations of the present disclosure may lack or have a reduced amount of naive conventional αβ-T cells or naive conventional CD3 + CD25 - CD45RA + T cells (Tcon). In some embodiments, the Tcon is CD45RA + . These cells can be discarded to result in the depletion of naive conventional αβ-T cells or naive conventional CD3 + CD25 - CD45RA + T cells (Tcon).

[0131] The cell populations of the present disclosure can be administered fresh after isolation. Cells freshly isolated from a donor ("fresh cells") can be administered to a recipient subject. The fresh cells can be stored in a buffer, e.g., CliniMACs PBS-EDTA buffer containing 0.5% human serum albumin, or Plasma-Lyte-A at pH 7.4 supplemented with 2% human serum albumin. The fresh cells can be stored at a reduced temperature (e.g., 2-8°C) without cryopreservation / freezing.

[0132] After obtaining a fresh cell population from a donor, the fresh cells can be stored 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 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 before being administered to a subject.

[0133] After obtaining a fresh cell population from a donor, the fresh cells can be stored for at most about 1 hour, at most about 2 hours, at most about 3 hours, at most about 4 hours, at most about 5 hours, at most about 6 hours, at most about 7 hours, at most about 8 hours, at most about 9 hours, at most about 10 hours, at most about 12 hours, at most about 14 hours, at most about 16 hours, at most about 18 hours, at most about 20, at most 22 hours, at most about 24 hours, at most about 30 hours, at most about 36 hours, at most about 40 hours, at most about 48 hours, at most about 60 hours, at most about 70 hours, at most about 72 hours, at most about 80 hours, at most about 90 hours, at most about 96 hours, at most about 120 hours, at most about 150 hours, at most about 200 hours or at most about 300 hours before being administered to a subject.

[0134] In some embodiments, after processing, one or more cell populations of the present disclosure (e.g., isolated CD45 +A population of cells can be formulated with one or more excipients. In some embodiments, the one or more excipients include a buffer, such as a transfer or infusion buffer. In some embodiments, the cell population is formulated at a neutral pH. In some embodiments, a population of HSPCs of the present disclosure or at least one dose of HSPCs is formulated with one or more excipients at a neutral pH. In some embodiments, a population of Tregs of the present disclosure or at least one dose of Tregs is formulated with one or more excipients at a neutral pH. In some embodiments, a population of Tmem of the present disclosure or at least one dose of Tmem is formulated with one or more excipients at a neutral pH. In some embodiments, a population of iNKTs of the present disclosure or at least one dose of iNKTs is formulated with one or more excipients at a neutral pH. In some embodiments, a population of HSPCs of the present disclosure or the dose of HSPCs and a population of Tregs of the present disclosure or the dose of Tregs are formulated with one or more excipients at a neutral pH. In some embodiments, a population of HSPCs of the present disclosure or the dose of HSPCs and a population of Tmem of the present disclosure or the dose of Tmem are formulated with one or more excipients at a neutral pH. In some embodiments, a population of HSPCs of the present disclosure or the dose of HSPCs and a population of iNKTs of the present disclosure or the dose of iNKTs are formulated with one or more excipients at a neutral pH. In some embodiments, a population of Tregs of the present disclosure or the dose of Tregs and a population of Tmem of the present disclosure or the dose of Tmem are formulated with one or more excipients at a neutral pH. In some embodiments, a population of Tregs of the present disclosure or the dose of Tregs and a population of iNKTs of the present disclosure or the dose of iNKTs are formulated with one or more excipients at a neutral pH. In some embodiments, a population of Tmem of the present disclosure or the dose of Tmem and a population of iNKTs of the present disclosure or the dose of iNKTs are formulated with one or more excipients at a neutral pH. In some embodiments, a population of HSPCs of the present disclosure or the dose of HSPCs, a population of Tregs of the present disclosure or the dose of Tregs, and a population of Tmem of the present disclosure or the dose of Tmem are formulated with one or more excipients at a neutral pH. In some embodiments, a population of HSPCs of the present disclosure or the dose of HSPCs, a population of Tregs of the present disclosure or the dose of Tregs, and a population of iNKTs of the present disclosure or the dose of iNKTs are formulated with one or more excipients at a neutral pH.In some embodiments, a population of HSPCs of the present disclosure or the dose of HSPCs, a population of Tmem or the dose of Tmem, and a population of iNKT or the dose of iNKT are formulated with one or more excipients at neutral pH. In some embodiments, a population of Tregs of the present disclosure or the dose of Tregs, a population of Tmem or the dose of Tmem, and a population of iNKT or the dose of iNKT are formulated with one or more excipients at neutral pH. In some embodiments, a population of HSPCs of the present disclosure or the dose of HSPCs, a population of Tregs or the dose of Tregs, a population of Tmem or the dose of Tmem, and a population of iNKT or the dose of iNKT are formulated with one or more excipients at neutral pH. In some embodiments, one or more excipients comprise one or more transfer buffers.

[0135] 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.

[0136] In some embodiments, one or more cell populations of the present disclosure (e.g., a population consisting of isolated CD45 + cells) can be formulated in one or more excipients. In some embodiments, one or more excipients can comprise one or more buffers. The buffer can be a transfer buffer or an infusion buffer. Transfer buffers suitable for use with the cell populations of the present disclosure include buffers having a range of about 120 mEq sodium to about 160 mEq sodium in milliequivalents (mEq) of sodium. In some embodiments, the transfer buffer of the present disclosure comprises 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.

[0137] Transfer buffers suitable for use with the cell populations of the present disclosure include buffers having an osmolality in the range of from about 270 mOsmol / L to about 320 mOsmol / L. In some embodiments, the osmolality of the transfer buffer of the present disclosure is 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.

[0138] In some embodiments, transfer buffers suitable for use with one or more cell populations of the present disclosure (e.g., a population consisting of isolated CD45 + cells) 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 of the present disclosure (e.g., a population consisting of isolated CD45 + cells) are formulated with a transfer buffer. In some embodiments, one or more cell populations of the present disclosure (e.g., a population consisting of isolated CD45 + cells) are formulated with a sufficient amount of PBS. In some embodiments, one or more cell populations of the present disclosure (e.g., a population consisting of isolated CD45 + cells) are formulated with a sufficient amount of human serum. In some embodiments, one or more cell populations of the present disclosure (e.g., a population consisting of isolated CD45 + cells) are formulated with a sufficient amount of PlasmaLyte (e.g., PlasmaLyte A).

[0139] In some embodiments, the transfer 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 concentration of the human carrier protein ranges from about 0.1 wt% to about 10 wt% by volume of the human carrier protein. In some embodiments, the concentration of the human carrier protein is about 0.1 wt%, about 0.2 wt%, about 0.3 wt%, about 0.4 wt%, about 0.5 wt%, about 0.6 wt%, about 0.7 wt%, about 0.8 wt%, about 0.9 wt%, about 1.0 wt%, about 1.1 wt%, about 1.2 wt%, about 1.3 wt%, about 1.4 wt%, about 1.5 wt%, about 1.6 wt%, about 1.7 wt%, about 1.8 wt%, about 1.9 wt%, about 2.0 wt%, about 2.1 wt%, about 2.2 wt%, about 2.3 wt%, about 2.4 wt%, about 2.5 wt%, about 2.6 wt%, about 2.7 wt%, about 2.8 wt%, about 2.9 wt%, about 3.0 wt%, about 3.1 wt%, about 3.2 wt%, about 3.3 wt%, about 3.4 wt%, about 3.5 wt%, about 3.6 wt%, about 3.7 wt%, about 3.8 wt%, about 3.9 wt%, about 4.0 wt%, about 4.1 wt%, about 4.2 wt%, about 4.3 wt%, about 4.4 wt%, about 4.5 wt%, about 4.6 wt%, about 4.7 wt%, about 4.8 wt%, about 4.9 wt%, about 5.0 wt%, about 5.1 wt%, about 5.2 wt%, about 5.3 wt%, about 5.4 wt%, about 5.5 wt%, about 5.6 wt%, about 5.7 wt%, about 5.8 wt%, about 5.9 wt%, about 6.0 wt%, about 6.1 wt%, about 6.2 wt%, about 6.3 wt%, about 6.4 wt%, about 6.5 wt%, about 6.6% by volume, approximately 6.7% by volume, approximately 6.8% by volume, approximately 6.9% by volume, approximately 7.0% by volume, approximately 7.1% by volume, approximately 7.2% by volume, approximately 7.3% by volume, approximately 7.4% by volume, approximately 7.5% by volume, approximately 7.6% by volume, approximately 7.7% by volume, approximately 7.8% by volume, approximately 7.9% by volume, approximately 8.0% by volume, approximately 8.1% by volume, approximately 8.2% by volume, approximately 8.3% by volume, approximately 8.4% by volume, approximately 8.5% by volume, approximately 8.6% by volume, approximately 8.7% by volume, approximately 8.8% by volume, approximately 8.9% by volume, approximately 9.0% by volume, approximately 9.1% by volume, approximately 9.2% by volume, approximately 9.3% by volume, approximately 9.4% by volume, approximately 9.5% by volume, approximately 9.6% by volume, approximately 9.7% by volume, approximately 9.8% by volume, approximately 9.9% by volume or approximately 10% by volume.

[0140] In some embodiments, one or more cell populations of the present disclosure (e.g., isolated CD45 +A population of cells) is formulated with an excipient such as the transfer buffer of the present disclosure in an amount sufficient to produce a volume ranging from about 5 mL to 1 L. In some embodiments, the cell population is formulated with an excipient such as the transfer buffer of the present disclosure in an amount sufficient to produce a volume ranging from about 5 mL to 1 L. In some embodiments, the cell population is formulated at the following volumes (e.g., with one or more excipients such as transfer buffer): 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 105 mL, about 110 mL, about 115 mL, about 120 mL, about 125 mL, about 130 mL, about 135 mL, about 140 mL, about 145 mL, about 150 mL, about 155 mL, about 160 mL, about 165 mL, about 170 mL, about 175 mL, about 180 mL, about 185 mL, about 190 mL, about 195 mL, about 200 mL, about 205 mL, about 210 mL, about 215 mL, about 220 mL, about 225 mL, about 230 mL, about 235 mL, about 240 mL, about 245 mL, about 250 mL, about 255 mL, about 260 mL, about 265 mL, about 270 mL, about 275 mL, about 280 mL, about 285 mL, about 290 mL, about 295 mL, about 300 mL, about 305 mL, about 310 mL, about 315 mL, about 320 mL, about 325 mL, about 330 mL, about 335 mL, about 340 mL, about 345 mL, about 350 mL, about 355 mL, about 360 mL, about 365 mL, about 370 mL, about 375 mL, about 380 mL, about 385 mL, about 390 mL, about 395 mL, about 400 mL, about 405 mL, about 410 mL, about 415 mL, about 420 mL, about 425 mL, about 430 mL, about 435 mL, about 440 mL, about 445 mL, about 450 mL, about 455 mL, about 460 mL, about 465 mL, about 470 mL, about 475 mL, about 480 mL, about 485 mL, about 490 mL, about 495 mL, about 500 mL, about 505 mL, about 510 mL, about 515 mL, about 520 mL, about 525 mL, about 530 mL, about 535 mL, about 540 mL, about 545 mL,About 550 mL, about 555 mL, about 560 mL, about 565 mL, about 570 mL, about 575 mL, about 580 mL, about 585 mL, about 590 mL, about 595 mL, about 600 mL, about 605 mL, about 610 mL, about 615 mL, about 620 mL, about 625 mL, about 630 mL, about 635 mL, about 640 mL, about 645 mL, about 650 mL, about 655 mL, about 660 mL, about 665 mL, about 670 mL, about 675 mL, about 680 mL, about 685 mL, about 690 mL, about 695 mL, about 700 mL, about 705 mL, about 710 mL, about 715 mL, about 720 mL, about 725 mL, about 730 mL, about 735 mL, about 740 mL, about 745 mL, about 750 mL, about 755 mL, about 760 mL, about 765 mL, about 770 mL, about 775 mL, about 780 mL, about 785 mL, about 790 mL, about 795 mL, about 800 mL, about 805 mL, about 810 mL, 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.,

[0141] The cell population of the present disclosure (e.g., isolated CD45 +Populations of cells (e.g., populations composed of isolated CD45 cells) can be cryopreserved. In some embodiments, cryopreservation can be beneficial to the methods disclosed herein. Cryopreservation can involve adding a preservative (e.g., DMSO) or one or more cryoprotectants and gradually cooling the cells in a controlled-rate freezer to prevent osmotic cell damage caused by ice crystal formation. Cryopreservation can involve commercial 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, hydroxyethyl starch, CRYOSTOR CS2, CRYOSTOR CS5, and CRYOSTOR CS10, or any combination thereof. In certain embodiments, the cryoprotectant of the present disclosure comprises DMSO. For example, in some embodiments, a cell population can be formulated for cryopreservation with a cryoprotectant that comprises an amount of DMSO in the range of from about 1% to about 15% by volume. Cryopreserved cells can be stored at low temperatures for a period ranging from several 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 in the methods of the present disclosure, such as before or after a sorting step, before or after a characterization step, such as determining cell viability or the concentration of a particular type of cell.

[0142] In some embodiments, once formulated, one or more cell populations of the present disclosure (e.g., populations composed of isolated CD45 + cells) can be placed in one or more containers. In certain aspects, the present disclosure relates to a system that comprises one or more containers that contain one or more cell populations of the present disclosure (e.g., populations composed of isolated CD45 + cells). In some embodiments, 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 (such as one or more transfer 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 cell population (e.g., a population composed of isolated CD45 +a population of cells). In some embodiments, the containers of the present disclosure include, but are not limited to, vials, syringes, bags (e.g., transfer bags), cryoprotectant containers, and any combination thereof. In some embodiments, the container is a bag that can be used for, for example, infusion, such as a transfer bag. 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.

[0143] 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.

[0144] donor

[0145] 1. General Information

[0146] Human leukocyte antigens (HLA), also widely known as major histocompatibility complex (MHC) antigens, can be protein molecules expressed on the surface of cells that can confer antigenic properties on the cells. HLA / MHC antigens are target molecules that can be recognized by T cells and natural killer (NK) cells as being derived from the same hematopoietic stem cell source as the immune effector cells ("self") or from another hematopoietic cell source ("non-self"). HLA class I antigens (A, B, and C in humans) can be expressed by the vast majority of cells, while HLA class II antigens (DR, DP, and DQ in humans) are mainly expressed on professional antigen-presenting cells. Both HLA classes can be associated with GVHD.

[0147] HLA antigens are encoded by highly polymorphic genes; for each HLA class I and class II gene there exists a series of alleles. Allelic products may differ in one or more amino acids in the α and / or β domains. A set of specific antibodies or nucleic acid reagents can be used to determine an individual's HLA haplotype, e.g., using leukocytes expressing class I and class II molecules to determine an individual's HLA haplotype. HLA alleles can be described at various levels of detail. Most names begin with HLA- and the locus name, followed by * and some number (an even number) of digits denoting the allele. The first two digits can specify a group of alleles. The third to fourth digits (when present) can specify synonymous alleles. The fifth to sixth digits (when present) can denote any synonymous mutations within the coding frame of the gene. The seventh and eighth digits (when present) can distinguish mutations outside the coding region. Letters such as L, N, Q, or S can follow the allele name to indicate expression level or other known relevant non-genomic data. Thus, a fully described allele can be up to nine digits long, excluding the HLA prefix and locus symbol.

[0148] A set of HLA alleles inherited from one parent forms a haplotype. HLA haploidentical can refer to a donor-recipient pair in which at least one chromosome matches between the donor and recipient at HLA-A, HLA-B, and HLA-DR. The haploidentical pair may match or may be mismatched at other alleles, e.g., other HLA genes on the other chromosome, or other histocompatibility loci on either chromosome. Such donors can often be found in families, e.g., a parent can be haploidentical to a child; and siblings may be haploidentical.

[0149] A cell population can be derived from a donor that has been HLA typed at any number of HLA alleles. The donor and the subject can be HLA matched, e.g., matched at all typed HLA alleles. The donor and the subject can be HLA mismatched, e.g., at least one HLA antigen can be mismatched between the donor and the recipient.

[0150] In some embodiments, related or unrelated donors and subjects can be HLA typed at six alleles consisting of HLA-A, HLA-B, and HLA-DR alleles. The donor and the subject can match at, e.g., 3 / 6, 4 / 6, 5 / 6, or 6 / 6 of the alleles. In some embodiments, the donor and the subject match at at least 5 / 6 alleles. In some embodiments, the donor and the subject match at 6 / 6 alleles.

[0151] In some embodiments, related or unrelated donors and recipients can be HLA typed at eight alleles consisting of HLA-A, HLA-B, HLA-C, and HLA-DR alleles (e.g., HLA-DRB1 allele). The donor and recipient can be matched, for example, at 4 / 8, 5 / 8, 6 / 8, 7 / 8, or 8 / 8 of the alleles. In some embodiments, the donor and recipient are matched at at least 6 / 8 alleles. In some embodiments, the donor and recipient are matched at at least 7 / 8 alleles. In some embodiments, the donor and recipient are matched at 8 / 8 alleles.

[0152] In some embodiments, related or unrelated donors and recipients can be HLA typed at ten alleles consisting of 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 recipient can be matched, for example, at 5 / 10, 6 / 10, 7 / 10, 8 / 10, 9 / 10, or 10 / 10 of the alleles. In some embodiments, the donor and recipient are matched at at least 7 / 10 alleles. In some embodiments, the donor and recipient are matched at at least 8 / 10 alleles. In some embodiments, the donor and recipient are matched at at least 9 / 10 alleles. In some embodiments, the donor and recipient are matched at 10 / 10 alleles.

[0153] In some embodiments, related or unrelated donors and recipients can be HLA typed at twelve alleles such as 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 recipient can be matched, for example, at 6 / 12, 7 / 12, 8 / 12, 9 / 12, 10 / 12, 11 / 12, or 12 / 12 of the alleles. In some embodiments, the donor and recipient are matched at at least 9 / 12 alleles. In some embodiments, the donor and recipient are matched at at least 10 / 12 alleles. In some embodiments, the donor and recipient are matched at at least 11 / 12 alleles. In some embodiments, the donor and recipient are matched at 12 / 12 alleles.

[0154] Cell populations can be generated from matched unrelated donors who are 8 / 8 matched for HLA-A, -B, -C, and -DRB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched unrelated donors who are 7 / 8 matched for HLA-A, -B, -C, and -DRB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched unrelated donors who are 6 / 8 matched for HLA-A, -B, -C, and -DRB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched unrelated donors who are 10 / 10 matched for HLA-A, -B, -C, -DQB1, and -DRB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched unrelated donors who are 9 / 10 matched for HLA-A, -B, -C, -DQB1, and -DRB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched unrelated donors who are 8 / 10 matched for HLA-A, -B, -C, -DQB1, and -DRB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched unrelated donors who are 7 / 10 matched for HLA-A, -B, -C, -DQB1, and -DRB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched unrelated donors who are 12 / 12 matched for HLA-A, -B, -C, -DQB1, -DRB1, and -DPB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched unrelated donors who are 11 / 12 matched for HLA-A, -B, -C, -DQB1, -DRB1, and -DPB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched unrelated donors who are 10 / 12 matched for HLA-A, -B, -C, -DQB1, -DRB1, and -DPB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched unrelated donors who are 9 / 12 matched for HLA-A, -B, -C, -DQB1, -DRB1, and -DPB1 (all typed using DNA-based high-resolution methods).

[0155] Cell populations can be generated from matched related donors who are 8 / 8 matched for HLA-A, -B, -C, and -DRB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched related donors who are 7 / 8 matched for HLA-A, -B, -C, and -DRB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched related donors who are 6 / 8 matched for HLA-A, -B, -C, and -DRB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched related donors who are 10 / 10 matched for HLA-A, -B, -C, -DQB1, and -DRB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched related donors who are 9 / 10 matched for HLA-A, -B, -C, -DQB1, and -DRB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched related donors who are 8 / 10 matched for HLA-A, -B, -C, -DQB1, and -DRB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched related donors who are 7 / 10 matched for HLA-A, -B, -C, -DQB1, and -DRB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched related donors who are 12 / 12 matched for HLA-A, -B, -C, -DQB1, -DRB1, and -DPB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched related donors who are 11 / 12 matched for HLA-A, -B, -C, -DQB1, -DRB1, and -DPB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched related donors who are 10 / 12 matched for HLA-A, -B, -C, -DQB1, -DRB1, and -DPB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched related donors who are 9 / 12 matched for HLA-A, -B, -C, -DQB1, -DRB1, and -DPB1 (all typed using DNA-based high-resolution methods).

[0156] Cell populations can be generated from matched parental donors that are 8 / 8 matched for HLA-A, -B, -C, and -DRB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched parental donors that are 7 / 8 matched for HLA-A, -B, -C, and -DRB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched parental donors that are 6 / 8 matched for HLA-A, -B, -C, and -DRB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched parental donors that are 10 / 10 matched for HLA-A, -B, -C, -DQB1, and -DRB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched parental donors that are 9 / 10 matched for HLA-A, -B, -C, -DQB1, and -DRB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched parental donors that are 8 / 10 matched for HLA-A, -B, -C, -DQB1, and -DRB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched parental donors that are 7 / 10 matched for HLA-A, -B, -C, -DQB1, and -DRB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched parental donors that are 12 / 12 matched for HLA-A, -B, -C, -DQB1, -DRB1, and -DPB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched parental donors that are 11 / 12 matched for HLA-A, -B, -C, -DQB1, -DRB1, and -DPB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched parental donors that are 10 / 12 matched for HLA-A, -B, -C, -DQB1, -DRB1, and -DPB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched parental donors that are 9 / 12 matched for HLA-A, -B, -C, -DQB1, -DRB1, and -DPB1 (all typed using DNA-based high-resolution methods).

[0157] Cell populations can be generated from matched sibling donors who are 8 / 8 matched for HLA-A, -B, -C, and -DRB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched sibling donors who are 7 / 8 matched for HLA-A, -B, -C, and -DRB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched sibling donors who are 6 / 8 matched for HLA-A, -B, -C, and -DRB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched sibling donors who are 10 / 10 matched for HLA-A, -B, -C, -DQB1, and -DRB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched sibling donors who are 9 / 10 matched for HLA-A, -B, -C, -DQB1, and -DRB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched sibling donors who are 8 / 10 matched for HLA-A, -B, -C, -DQB1, and -DRB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched sibling donors who are 7 / 10 matched for HLA-A, -B, -C, -DQB1, -DRB1, and -DPB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched sibling donors who are 12 / 12 matched for HLA-A, -B, -C, -DQB1, -DRB1, and -DPB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched sibling donors who are 11 / 12 matched for HLA-A, -B, -C, -DQB1, -DRB1, and -DPB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched sibling donors who are 10 / 12 matched for HLA-A, -B, -C, -DQB1, -DRB1, and -DPB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched sibling donors who are 9 / 12 matched for HLA-A, -B, -C, -DQB1, -DRB1, and -DPB1 (all typed using DNA-based high-resolution methods).

[0158] Cell populations can be generated from matched sibling donors who are 8 / 8 matched for HLA-A, -B, -C, and -DRB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched sibling donors who are 7 / 8 matched for HLA-A, -B, -C, and -DRB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched sibling donors who are 6 / 8 matched for HLA-A, -B, -C, and -DRB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched sibling donors who are 10 / 10 matched for HLA-A, -B, -C, -DQB1, and -DRB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched sibling donors who are 9 / 10 matched for HLA-A, -B, -C, -DQB1, and -DRB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched sibling donors who are 8 / 10 matched for HLA-A, -B, -C, -DQB1, and -DRB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched sibling donors who are 7 / 10 matched for HLA-A, -B, -C, -DQB1, and -DRB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched offspring donors who are 12 / 12 matched for HLA-A, -B, -C, -DQB1, -DRB1, and -DPB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched offspring donors who are 11 / 12 matched for HLA-A, -B, -C, -DQB1, -DRB1, and -DPB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched offspring donors who are 10 / 12 matched for HLA-A, -B, -C, -DQB1, -DRB1, and -DPB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched offspring donors who are 9 / 12 matched for HLA-A, -B, -C, -DQB1, -DRB1, and -DPB1 (all typed using DNA-based high-resolution methods).

[0159] Cell populations can be generated from matched grandparental donors that are 8 / 8 matched for HLA-A, -B, -C, and -DRB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched grandparental donors that are 7 / 8 matched for HLA-A, -B, -C, and -DRB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched grandparental donors that are 6 / 8 matched for HLA-A, -B, -C, and -DRB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched grandparental donors that are 10 / 10 matched for HLA-A, -B, -C, -DQB1, and -DRB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched grandparental donors that are 9 / 10 matched for HLA-A, -B, -C, -DQB1, and -DRB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched grandparental donors that are 8 / 10 matched for HLA-A, -B, -C, -DQB1, and -DRB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched grandparental donors that are 7 / 10 matched for HLA-A, -B, -C, -DQB1, -DRB1, and -DPB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched grandparental donors that are 12 / 12 matched for HLA-A, -B, -C, -DQB1, -DRB1, and -DPB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched grandparental donors that are 11 / 12 matched for HLA-A, -B, -C, -DQB1, -DRB1, and -DPB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched grandparental donors that are 10 / 12 matched for HLA-A, -B, -C, -DQB1, -DRB1, and -DPB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched grandparental donors that are 9 / 12 matched for HLA-A, -B, -C, -DQB1, -DRB1, and -DPB1 (all typed using DNA-based high-resolution methods).

[0160] Cell populations can be generated from matched grandchild donors who are 8 / 8 matched for HLA-A, -B, -C, and -DRB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched grandchild donors who are 7 / 8 matched for HLA-A, -B, -C, and -DRB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched grandchild donors who are 6 / 8 matched for HLA-A, -B, -C, and -DRB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched grandchild donors who are 10 / 10 matched for HLA-A, -B, -C, -DQB1, and -DRB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched grandchild donors who are 9 / 10 matched for HLA-A, -B, -C, -DQB1, and -DRB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched grandchild donors who are 8 / 10 matched for HLA-A, -B, -C, -DQB1, and -DRB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched grandchild donors who are 7 / 10 matched for HLA-A, -B, -C, -DQB1, -DRB1, and -DPB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched grandchild donors who are 12 / 12 matched for HLA-A, -B, -C, -DQB1, -DRB1, and -DPB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched grandchild donors who are 11 / 12 matched for HLA-A, -B, -C, -DQB1, -DRB1, and -DPB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched grandchild donors who are 10 / 12 matched for HLA-A, -B, -C, -DQB1, -DRB1, and -DPB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched grandchild donors who are 9 / 12 matched for HLA-A, -B, -C, -DQB1, -DRB1, and -DPB1 (all typed using DNA-based high-resolution methods).

[0161] Cell populations can be generated from matched aunt donors that are 8 / 8 matched for HLA-A, -B, -C, and -DRB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched aunt donors that are 7 / 8 matched for HLA-A, -B, -C, and -DRB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched aunt donors that are 6 / 8 matched for HLA-A, -B, -C, and -DRB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched aunt donors that are 10 / 10 matched for HLA-A, -B, -C, -DQB1, and -DRB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched aunt donors that are 9 / 10 matched for HLA-A, -B, -C, -DQB1, and -DRB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched aunt donors that are 8 / 10 matched for HLA-A, -B, -C, -DQB1, and -DRB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched aunt donors that are 7 / 10 matched for HLA-A, -B, -C, -DQB1, -DRB1, and -DPB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched aunt donors that are 12 / 12 matched for HLA-A, -B, -C, -DQB1, -DRB1, and -DPB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched aunt donors that are 11 / 12 matched for HLA-A, -B, -C, -DQB1, -DRB1, and -DPB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched aunt donors that are 10 / 12 matched for HLA-A, -B, -C, -DQB1, -DRB1, and -DPB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched aunt donors that are 9 / 12 matched for HLA-A, -B, -C, -DQB1, -DRB1, and -DPB1 (all typed using DNA-based high-resolution methods).

[0162] Cell populations can be generated from matched uncle donors who are 8 / 8 matched for HLA-A, -B, -C, and -DRB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched uncle donors who are 7 / 8 matched for HLA-A, -B, -C, and -DRB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched uncle donors who are 6 / 8 matched for HLA-A, -B, -C, and -DRB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched uncle donors who are 10 / 10 matched for HLA-A, -B, -C, -DQB1, and -DRB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched uncle donors who are 9 / 10 matched for HLA-A, -B, -C, -DQB1, and -DRB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched uncle donors who are 8 / 10 matched for HLA-A, -B, -C, -DQB1, and -DRB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched uncle donors who are 7 / 10 matched for HLA-A, -B, -C, -DQB1, -DRB1, and -DPB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched uncle donors who are 12 / 12 matched for HLA-A, -B, -C, -DQB1, -DRB1, and -DPB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched uncle donors who are 11 / 12 matched for HLA-A, -B, -C, -DQB1, -DRB1, and -DPB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched uncle donors who are 10 / 12 matched for HLA-A, -B, -C, -DQB1, -DRB1, and -DPB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched uncle donors who are 9 / 12 matched for HLA-A, -B, -C, -DQB1, -DRB1, and -DPB1 (all typed using DNA-based high-resolution methods).

[0163] Cell populations can be generated from matched cousin donors who are 8 / 8 matched for HLA-A, -B, -C, and -DRB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched cousin donors who are 7 / 8 matched for HLA-A, -B, -C, and -DRB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched cousin donors who are 6 / 8 matched for HLA-A, -B, -C, and -DRB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched cousin donors who are 10 / 10 matched for HLA-A, -B, -C, -DQB1, and -DRB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched cousin donors who are 9 / 10 matched for HLA-A, -B, -C, -DQB1, and -DRB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched cousin donors who are 8 / 10 matched for HLA-A, -B, -C, -DQB1, and -DRB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched cousin donors who are 7 / 10 matched for HLA-A, -B, -C, -DQB1, -DRB1, and -DPB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched cousin donors who are 12 / 12 matched for HLA-A, -B, -C, -DQB1, -DRB1, and -DPB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched cousin donors who are 11 / 12 matched for HLA-A, -B, -C, -DQB1, -DRB1, and -DPB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched cousin donors who are 10 / 12 matched for HLA-A, -B, -C, -DQB1, -DRB1, and -DPB1 (all typed using DNA-based high-resolution methods). Cell populations can be generated from matched cousin donors who are 9 / 12 matched for HLA-A, -B, -C, -DQB1, -DRB1, and -DPB1 (all typed using DNA-based high-resolution methods). 2. Specific Embodiments

[0165] In some embodiments, HLA mismatches occur because allogeneic related or unrelated donors are homozygous for HLA alleles, while recipient subjects are heterozygous for HLA alleles. In some embodiments, HLA mismatches occur because allogeneic related or unrelated donors are heterozygous for HLA alleles, while recipient subjects are homozygous for HLA alleles. In some embodiments, HLA mismatches occur because both allogeneic related or unrelated donors and recipient subjects are heterozygous for HLA alleles.

[0166] In various embodiments, the cell populations of the present disclosure are allogeneic relative to a human subject. In some embodiments, the cell populations of the present disclosure are obtained from a donor who is HLA-matched relative to the human subject. In embodiments, the cell populations of the present disclosure are obtained from a donor who is HLA-mismatched relative to the human subject. In various embodiments, the cell populations of the present disclosure are obtained from a haploidentical donor relative to the human subject.

[0167] One or more cell populations of the present disclosure can be obtained from a single donor, for example, from apheresis of mobilized peripheral blood of a single donor. HSPC, Treg, Tcon, iNKT, Tmem, or any combination thereof can be obtained from a single donor.

[0168] One or more cell populations of the present disclosure can be obtained from one 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. The cell populations of the present disclosure can be obtained from multiple donors, for example, from apheresis of mobilized peripheral blood of multiple donors. HSPC can be obtained from multiple donors. Treg can be obtained from multiple donors. Tmem can be obtained from multiple donors. iNKT can be obtained from multiple donors.

[0169] In embodiments, the respective cell populations are provided as separate cell populations and are derived from a single human blood donor.

[0170] The cell populations can comprise cells from one or more donors who have all been HLA typed, for example, to determine the degree of HLA matching to a subject who will receive the cell populations.

[0171] In some embodiments, the cell populations, the cell populations enriched for Treg and / or Tmem are allogeneic relative to a human subject. In some embodiments, depleting naive conventional αβ-T cells or naive conventional CD3 + CD25 - CD45RA +The cell population of T cells (Tcon) is allogeneic with respect to a human subject.

[0172] In some embodiments, the cell population enriched for Tregs and / or Tmem is obtained from a donor who is HLA-matched to the human subject. In some embodiments, naive conventional αβ-T cells or naive conventional CD3 + CD25 - CD45RA + The cell population of T cells (Tcon) is obtained from a donor who is HLA-matched to the human subject.

[0173] In some embodiments, the cell population enriched for Tregs and / or Tmem is obtained from a donor who is HLA-mismatched to the human subject. In some embodiments, naive conventional αβ-T cells or naive conventional CD3 + CD25 - CD45RA + The cell population of T cells (Tcon) is obtained from a donor who is HLA-mismatched to the human subject.

[0174] In some embodiments, the cell population enriched for Tregs and / or Tmem is obtained from a donor who is haploidentical to the human subject. In some embodiments, naive conventional αβ-T cells or naive conventional CD3 + CD25 - CD45RA + The cell population of T cells (Tcon) is obtained from a donor who is haploidentical to the human subject.

[0175] The cell population can be derived from an allogeneic donor. The cell population can be generated by a donor who is a first-degree blood relative of the subject. The cell population can be generated by a donor who is a second-degree blood relative of the subject. The cell population can be generated by a donor who is unrelated to the subject. The cell population can be generated by a donor who is HLA-matched to the recipient subject. The cell population can be generated by a donor who is HLA-mismatched to the recipient subject. The cell population can be generated by a donor who is haploidentical to the recipient subject. The cell population can be generated by a donor who is related to the recipient subject, e.g., parent, child, sibling, grandparent, grandchild, aunt, uncle, or cousin. The cell population can be generated by a donor who is at least 16 years old. The cell population can be generated by a donor who is at least 18 years old.

[0176] A cell population can be generated from a donor who meets the donor eligibility criteria of living, leukocyte-rich cells or tissues as defined in 21 CFR § 1271.2018 and related FDA industry guidance.For example, a cell population can be generated from donors meeting the eligibility criteria outlined in 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.A cell population can be generated from a donor (NMDP donor) meeting any donation criteria as defined by the standard NMDP guidelines.

[0177] A cell population can be generated from a donor who does not exhibit signs of active infection. A cell population can be generated from a donor who is not seropositive for HIV-1 or -2, HTLV-1 or -2. A cell population can be generated from a donor who is not positive for anti-hepatitis C (HCV) antibodies or HCV NAT. A cell population can be generated from a donor tested negative for chronic HBV infection. A cell population can be generated from a donor who does not have a high likelihood of Zika virus infection as defined by any of the following: (i) a medical diagnosis of Zika virus infection within the past 6 months; (ii) residence or travel within an area of active Zika virus transmission within the past 6 months; (iii) unprotected sexual intercourse within the past 6 months with a person known to have any of the risk factors (i) or (ii). A cell population can be generated from a donor without signs or symptoms consistent with active Zika virus infection.

[0178] One or more cell populations of the present disclosure can be obtained from a single donor, e.g., from apheresis of mobilized peripheral blood of a single donor. HSPC, Treg, naïve conventional αβ-T cells, or naïve conventional CD3 + CD25 - CD45RA + T cells (Tcon), iNKT, Tmem, or any combination thereof can be obtained from a single donor. The cell populations provided in the present disclosure can be obtained from multiple donors, e.g., from apheresis of mobilized peripheral blood of multiple donors. HSPC can be obtained from multiple donors. Treg can be obtained from multiple donors. Naïve conventional αβ-T cells or naïve 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. Naïve conventional αβ-T cells or naïve conventional CD3 + CD25 - CD45RA + T cells (Tcon) can be depleted from one or more cell populations of the present disclosure.

[0179] Dose of cells

[0180] The dose of a cell population administered to a subject (e.g., a human subject) can be based on the weight of the subject. In some embodiments, the weight of the subject can be used to determine the dose of one or more cell populations to be administered to the subject. In some embodiments, the cell dose can be based on a calculated weight (e.g., ideal body weight or IBW) used for dose calculation for the subject rather than its actual weight (e.g., actual body weight). In some embodiments, IBW is the preferred method for dose calculation to avoid incorrect cell doses due to excessive body fat and / or muscle mass. In some embodiments, the ideal body weight of the subject can be calculated using their height and gender. In some embodiments, the ideal body weight of the subject can be calculated using Devine's method (DeVine 1974). In some embodiments, other methods for calculating the subject's IBW can be used. For example, other methods for determining the body fat percentage of the subject. In some embodiments, if the actual body weight of the subject is greater than 120% of the IBW, the dose of one or more cell populations of the present disclosure (e.g., a population composed of isolated CD45 + cells) can be based on the adjusted ideal body weight (AIBW) of the subject.

[0181] In some embodiments, the weight of the human subject of the present disclosure ranges from about 4 kilograms (kg) to about 200 kilograms (kg). In some embodiments, the weight of the human subject is about 4 kg, about 5 kg, about 6 kg, about 7 kg, about 8 kg, about 9 kg, about 10 kg, about 11 kg, about 12 kg, about 13 kg, about 14 kg, about 15 kg, about 16 kg, about 17 kg, about 18 kg, about 19 kg, about 20 kg, about 21 kg, about 22 kg, about 23 kg, about 24 kg, about 25 kg, about 26 kg, about 27 kg, about 28 kg, about 29 kg, about 30 kg, about 31 kg, about 32 kg, about 33 kg, about 34 kg, about 35 kg, about 36 kg, about 37 kg, about 38 kg, about 39 kg, about 40 kg, about 41 kg, about 42 kg, about 43 kg, about 44 kg, about 45 kg, about 46 kg, about 47 kg, about 48 kg, about 49 kg, about 50 kg, about 51 kg, about 52 kg, about 53 kg, about 54 kg, about 55 kg, about 56 kg, about 57 kg, about 58 kg, about 59 kg, about 60 kg, about 61 kg, about 62 kg, about 63 kg, about 64 kg, about 65 kg, about 66 kg, about 67 kg, about 68 kg, about 69 kg, about 70 kg, about 71 kg, about 72 kg, about 73 kg, about 74 kg, about 75 kg, about 76 kg, about 77 kg, about 78 kg, about 79 kg, about 80 kg, about 81 kg, about 82 kg, about 83 kg, about 84 kg, about 85 kg, about 86 kg, about 87 kg, about 88 kg, about 89 kg, about 90 kg, about 91 kg, about 92 kg, about 93 kg, about 94 kg, about 95 kg, about 96 kg, about 97 kg, about 98 kg, about 99 kg, about 100 kg, about 105 kg, about 110 kg, about 115 kg, about 120 kg, about 125 kg, about 130 kg, about 135 kg, about 140 kg, about 145 kg, about 150 kg, about 155 kg, about 160 kg, about 165 kg, about 170 kg, about 175 kg, about 180 kg, about 185 kg, about 190 kg, about 195 kg or about 200 kg.

[0182] HSPC

[0183] In some embodiments, the cell population of the present disclosure that comprises HSPCs or comprises at least one dose of HSPCs comprises from about 1x10 4 to about 1x10 9 HSPCs per kilogram of the actual or ideal body weight of a human subject receiving the treatment or cell therapy product of the present disclosure. In some embodiments, the cell population that comprises HSPCs or comprises at least one dose of HSPCs comprises from about 1x10 4 to about 1x10 9 HSPCs per kilogram of IBW of a human subject. ...

Claims

1. A cell therapy product comprising a population of isolated CD45 + cells, wherein the population of isolated CD45 + cells comprises: a) a dose of from about 1.0x10 5 to about 1.0x10 8 CD34 + hematopoietic stem and progenitor cells (HSPCs) per kilogram of body weight of a human subject receiving the product or a total dose of from about 5.0x10 5 to about 1.5x10 10 CD34 + hematopoietic stem and progenitor cells (HSPCs); b) a dose of from about 1.0x10 5 to about 1.0x10 8 CD45RA - memory T cells (Tmem) per kilogram of body weight of the human subject receiving the product or a total dose of from about 5.0x10 5 to about 1.5x10 10 CD45RA - memory T cells (Tmem); and c) a dose of from about 1.0x10 5 to about 2.0x10 7 fresh CD4 + CD25 + CD127 dim regulatory T cells (Treg) per kilogram of body weight of the human subject receiving the product or a total dose of from about 5.0x10 5 to about 3.0x10 9 isolated fresh + CD4 + CD25 + CD127 dim regulatory T cells (Treg), wherein the cell therapy product has depleted naïve conventional CD3 + CD25 - CD45RA + T cells (Tcon) to comprise less than about 5.0x10 5 naïve conventional CD3 + CD25 - CD45RA + T cells (Tcon) per kilogram of body weight of the human subject receiving the product, less than about 6.0x10 7 total naïve conventional CD3+ CD25 - CD45RA + T cells (Tcon) or less than about 1.0x10 6 total naive conventional CD3 + CD25 - CD45RA + T cells (Tcon), and wherein the population consisting of isolated CD45 + cells is formulated with an excipient at neutral pH.

2. The cell therapy product according to claim 1, wherein: a) The dose of the HSPCs comprises the following doses: about 1.0x10 5 or more HSPCs per kilogram of body weight of the human subject receiving the product, about 2.0x10 5 or more HSPCs per kilogram of body weight of the human subject receiving the product, about 3.0x10 5 or more HSPCs per kilogram of body weight of the human subject receiving the product, about 4.0x10 5 or more HSPCs per kilogram of body weight of the human subject receiving the product, about 5.0x10 5 or more HSPCs per kilogram of body weight of the human subject receiving the product, about 6.0x10 5 or more HSPCs per kilogram of body weight of the human subject receiving the product, about 7.0x10 5 or more HSPCs per kilogram of body weight of the human subject receiving the product, about 8.0x10 5 or more HSPCs per kilogram of body weight of the human subject receiving the product, about 9.0x10 5 or more HSPCs per kilogram of body weight of the human subject receiving the product, about 1.0x10 6 or more HSPCs per kilogram of body weight of the human subject receiving the product, about 1.5x10 6 or more HSPCs per kilogram of body weight of the human subject receiving the product, about 2.0x10 6 or more HSPCs per kilogram of body weight of the human subject receiving the product, about 2.5x10 6 or more HSPCs per kilogram of body weight of the human subject receiving the product, about 3.0x10 6 or more HSPCs per kilogram of body weight of the human subject receiving the product, about 3.5x10 6 or more HSPCs per kilogram of body weight of the human subject receiving the product, about 4.0x10 6 or more HSPCs per kilogram of body weight of the human subject receiving the product, about 4.5x10 6 or more HSPCs per kilogram of body weight of the human subject receiving the product, about 5.0x10 6 or more HSPCs per kilogram of body weight of the human subject receiving the product, about 5.5x10 6 One or more HSPCs, approximately 6.0x10 per kilogram of body weight of the human subject receiving the product 6 One or more HSPCs, approximately 6.5x10 per kilogram of body weight of the human subject receiving the product 6 One or more HSPCs, approximately 7.0x10 per kilogram of body weight of the human subject receiving the product 6 One or more HSPCs, approximately 7.5x10 per kilogram of body weight of the human subject receiving the product 6 One or more HSPCs, approximately 8.0x10 per kilogram of body weight of the human subject receiving the product 6 One or more HSPCs, approximately 8.5x10 per kilogram of body weight of the human subject receiving the product 6 One or more HSPCs, approximately 9.0x10 per kilogram of body weight of the human subject receiving the product 6 One or more HSPCs, approximately 9.5x10 per kilogram of body weight of the human subject receiving the product 6 One or more HSPCs, approximately 1.0x10 per kilogram of body weight of the human subject receiving the product 7 One or more HSPCs, approximately 1.5x10 per kilogram of body weight of the human subject receiving the product 7 One or more HSPCs, approximately 2.0x10 per kilogram of body weight of the human subject receiving the product 7 One or more HSPCs, approximately 2.5x10 per kilogram of body weight of the human subject receiving the product 7 One or more HSPCs, approximately 3.0x10 per kilogram of body weight of the human subject receiving the product 7 One or more HSPCs, approximately 3.5x10 per kilogram of body weight of the human subject receiving the product 7 One or more HSPCs, approximately 4.0x10 per kilogram of body weight of the human subject receiving the product 7 One or more HSPCs, approximately 4.5x10 per kilogram of body weight of the human subject receiving the product 7 One or more HSPCs, approximately 5.0x10 per kilogram of body weight of the human subject receiving the product 7 One or more HSPCs, approximately 5.5x10 per kilogram of body weight of the human subject receiving the product 7 One or more HSPCs, approximately 6.0x10 per kilogram of body weight of the human subject receiving the product 7 One or more HSPCs, approximately 6.5x10 per kilogram of body weight of the human subject receiving the product 7 One or more HSPCs, approximately 7.0x10 per kilogram of body weight of the human subject receiving the product 7 One or more HSPCs, approximately 7.5x10 per kilogram of body weight of the human subject receiving the product 7 One or more HSPCs, approximately 8.0x10 per kilogram of body weight of the human subject receiving the product 7 One or more HSPCs, approximately 8.5x10 per kilogram of body weight of the human subject receiving the product 7 One or more HSPCs, approximately 9.0x10 per kilogram of body weight of the human subject receiving the product 7 One or more HSPCs, approximately 9.5x10 per kilogram of body weight of the human subject receiving the product 7 One or more HSPCs or approximately 1.0x10 per kilogram of body weight of the human subject receiving the product 8 One or more HSPCs; and / or b) The dose of the HSPCs includes the following total doses: approximately 5.0x10 5 or more HSPCs, approximately 6.0x10 5 or more HSPCs, approximately 7.0x10 5 or more HSPCs, approximately 8.0x10 5 or more HSPCs, approximately 9.0x10 5 or more HSPCs, approximately 1.0x10 6 or more HSPCs, approximately 1.5x10 6 or more HSPCs, approximately 2.0x10 6 or more HSPCs, approximately 2.5x10 6 or more HSPCs, approximately 3.0x10 6 or more HSPCs, approximately 3.5x10 6 or more HSPCs, approximately 4.0x10 6 or more HSPCs, approximately 4.5x10 6 or more HSPCs, approximately 5.0x10 6 or more HSPCs, approximately 5.5x10 6 or more HSPCs, approximately 6.0x10 6 or more HSPCs, approximately 6.5x10 6 or more HSPCs, approximately 7.0x10 6 or more HSPCs, approximately 7.5x10 6 or more HSPCs, approximately 8.0x10 6 or more HSPCs, approximately 8.5x10 6 or more HSPCs, approximately 9.0x10 6 or more HSPCs, approximately 9.5x10 6 or more HSPCs, approximately 1.0x10 7 or more HSPCs, approximately 1.5x10 7 or more HSPCs, approximately 2.0x10 7 or more HSPCs, approximately 2.5x10 7 or more HSPCs, approximately 3.0x10 7 or more HSPCs, approximately 3.5x10 7 or more HSPCs, approximately 4.0x10 7 or more HSPCs, approximately 4.5x10 7 or more HSPCs, approximately 5.0x10 7 One or more HSPCs, approximately 5.5x10 7 One or more HSPCs, approximately 6.0x10 7 One or more HSPCs, approximately 6.5x10 7 One or more HSPCs, approximately 7.0x10 7 One or more HSPCs, approximately 7.5x10 7 One or more HSPCs, approximately 8.0x10 7 One or more HSPCs, approximately 8.5x10 7 One or more HSPCs, approximately 9.0x10 7 One or more HSPCs, approximately 9.5x10 7 One or more HSPCs, approximately 1.0x10 8 One or more HSPCs, approximately 1.5x10 8 One or more HSPCs, approximately 2.0x10 8 One or more HSPCs, approximately 2.5x10 8 One or more HSPCs, approximately 3.0x10 8 One or more HSPCs, approximately 3.5x10 8 One or more HSPCs, approximately 4.0x10 8 One or more HSPCs, approximately 4.5x10 8 One or more HSPCs, approximately 5.0x10 8 One or more HSPCs, approximately 5.5x10 8 One or more HSPCs, approximately 6.0x10 8 One or more HSPCs, approximately 6.5x10 8 One or more HSPCs, approximately 7.0x10 8 One or more HSPCs, approximately 7.5x10 8 One or more HSPCs, approximately 8.0x10 8 One or more HSPCs, approximately 8.5x10 8 One or more HSPCs, approximately 9.0x10 8 One or more HSPCs, approximately 9.5x10 8 One or more HSPCs, approximately 1.0x10 9 One or more HSPCs, approximately 1.5x10 9 One or more HSPCs, approximately 2.0x10 9 One or more HSPCs, approximately 2.5x10 9 One or more HSPCs, approximately 3.0x10 9 one or more HSPCs, approximately 3.5x10 9 one or more HSPCs, approximately 4.0x10 9 one or more HSPCs, approximately 4.5x10 9 one or more HSPCs, approximately 5.0x10 9 one or more HSPCs, approximately 5.5x10 9 one or more HSPCs, approximately 6.0x10 9 one or more HSPCs, approximately 6.5x10 9 one or more HSPCs, approximately 7.0x10 9 one or more HSPCs, approximately 7.5x10 9 one or more HSPCs, approximately 8.0x10 9 one or more HSPCs, approximately 8.5x10 9 one or more HSPCs, approximately 9.0x10 9 one or more HSPCs, approximately 9.5x10 9 one or more HSPCs, approximately 1.0x10 10 one or more HSPCs or approximately 1.5x10 10 one or more HSPCs; and / or c) The dose of the Tmem comprises the following doses: about 1.0x10 5 or more Tmem per kg of body weight of the human subject receiving the product, about 2.0x10 5 or more Tmem per kg of body weight of the human subject receiving the product, about 3.0x10 5 or more Tmem per kg of body weight of the human subject receiving the product, about 4.0x10 5 or more Tmem per kg of body weight of the human subject receiving the product, about 5.0x10 5 or more Tmem per kg of body weight of the human subject receiving the product, about 6.0x10 5 or more Tmem per kg of body weight of the human subject receiving the product, about 7.0x10 5 or more Tmem per kg of body weight of the human subject receiving the product, about 8.0x10 5 or more Tmem per kg of body weight of the human subject receiving the product, about 9.0x10 5 or more Tmem per kg of body weight of the human subject receiving the product, about 1.0x10 6 or more Tmem per kg of body weight of the human subject receiving the product, about 1.5x10 6 or more Tmem per kg of body weight of the human subject receiving the product, about 2.0x10 6 or more Tmem per kg of body weight of the human subject receiving the product, about 2.5x10 6 or more Tmem per kg of body weight of the human subject receiving the product, about 3.0x10 6 or more Tmem per kg of body weight of the human subject receiving the product, about 3.5x10 6 or more Tmem per kg of body weight of the human subject receiving the product, about 4.0x10 6 or more Tmem per kg of body weight of the human subject receiving the product, about 4.5x10 6 or more Tmem per kg of body weight of the human subject receiving the product, about 5.0x10 6 or more Tmem per kg of body weight of the human subject receiving the product, about 5.5x10 6 One or more Tmem, approximately 6.0x10 per kilogram of body weight of the human subject receiving the product 6 One or more Tmem, approximately 6.5x10 per kilogram of body weight of the human subject receiving the product 6 One or more Tmem, approximately 7.0x10 per kilogram of body weight of the human subject receiving the product 6 One or more Tmem, approximately 7.5x10 per kilogram of body weight of the human subject receiving the product 6 One or more Tmem, approximately 8.0x10 per kilogram of body weight of the human subject receiving the product 6 One or more Tmem, approximately 8.5x10 per kilogram of body weight of the human subject receiving the product 6 One or more Tmem, approximately 9.0x10 per kilogram of body weight of the human subject receiving the product 6 One or more Tmem, approximately 9.5x10 per kilogram of body weight of the human subject receiving the product 6 One or more Tmem, approximately 1.0x10 per kilogram of body weight of the human subject receiving the product 7 One or more Tmem, approximately 1.5x10 per kilogram of body weight of the human subject receiving the product 7 One or more Tmem, approximately 2.0x10 per kilogram of body weight of the human subject receiving the product 7 One or more Tmem, approximately 2.5x10 per kilogram of body weight of the human subject receiving the product 7 One or more Tmem, approximately 3.0x10 per kilogram of body weight of the human subject receiving the product 7 One or more Tmem, approximately 3.5x10 per kilogram of body weight of the human subject receiving the product 7 One or more Tmem, approximately 4.0x10 per kilogram of body weight of the human subject receiving the product 7 One or more Tmem, approximately 4.5x10 per kilogram of body weight of the human subject receiving the product 7 One or more Tmem, approximately 5.0x10 per kilogram of body weight of the human subject receiving the product 7 One or more Tmem, approximately 5.5x10 per kilogram of body weight of the human subject receiving the product 7 One or more Tmem, approximately 6.0x10 per kilogram of body weight of the human subject receiving the product 7 One or more Tmems, approximately 6.5x10 per kilogram of body weight of the human subject receiving the product 7 One or more Tmems, approximately 7.0x10 per kilogram of body weight of the human subject receiving the product 7 One or more Tmems, approximately 7.5x10 per kilogram of body weight of the human subject receiving the product 7 One or more Tmems, approximately 8.0x10 per kilogram of body weight of the human subject receiving the product 7 One or more Tmems, approximately 8.5x10 per kilogram of body weight of the human subject receiving the product 7 One or more Tmems, approximately 9.0x10 per kilogram of body weight of the human subject receiving the product 7 One or more Tmems, approximately 9.5x10 per kilogram of body weight of the human subject receiving the product 7 One or more Tmems or approximately 1.0x10 per kilogram of body weight of the human subject receiving the product 8 One or more Tmems; and / or d) The dose of the Tmem includes the following total doses: approximately 5.0x10 5 or more Tmems, approximately 6.0x10 5 or more Tmems, approximately 7.0x10 5 or more Tmems, approximately 8.0x10 5 or more Tmems, approximately 9.0x10 5 or more Tmems, approximately 1.0x10 6 or more Tmems, approximately 1.5x10 6 or more Tmems, approximately 2.0x10 6 or more Tmems, approximately 2.5x10 6 or more Tmems, approximately 3.0x10 6 or more Tmems, approximately 3.5x10 6 or more Tmems, approximately 4.0x10 6 or more Tmems, approximately 4.5x10 6 or more Tmems, approximately 5.0x10 6 or more Tmems, approximately 5.5x10 6 or more Tmems, approximately 6.0x10 6 or more Tmems, approximately 6.5x10 6 or more Tmems, approximately 7.0x10 6 or more Tmems, approximately 7.5x10 6 or more Tmems, approximately 8.0x10 6 or more Tmems, approximately 8.5x10 6 or more Tmems, approximately 9.0x10 6 or more Tmems, approximately 9.5x10 6 or more Tmems, approximately 1.0x10 7 or more Tmems, approximately 1.5x10 7 or more Tmems, approximately 2.0x10 7 or more Tmems, approximately 2.5x10 7 or more Tmems, approximately 3.0x10 7 or more Tmems, approximately 3.5x10 7 or more Tmems, approximately 4.0x10 7 or more Tmems, approximately 4.5x10 7 or more Tmems, approximately 5.0x10 7 one or more Tmem, approximately 5.5x10 7 one or more Tmem, approximately 6.0x10 7 one or more Tmem, approximately 6.5x10 7 one or more Tmem, approximately 7.0x10 7 one or more Tmem, approximately 7.5x10 7 one or more Tmem, approximately 8.0x10 7 one or more Tmem, approximately 8.5x10 7 one or more Tmem, approximately 9.0x10 7 one or more Tmem, approximately 9.5x10 7 one or more Tmem, approximately 1.0x10 8 one or more Tmem, approximately 1.5x10 8 one or more Tmem, approximately 2.0x10 8 one or more Tmem, approximately 2.5x10 8 one or more Tmem, approximately 3.0x10 8 one or more Tmem, approximately 3.5x10 8 one or more Tmem, approximately 4.0x10 8 one or more Tmem, approximately 4.5x10 8 one or more Tmem, approximately 5.0x10 8 one or more Tmem, approximately 5.5x10 8 one or more Tmem, approximately 6.0x10 8 one or more Tmem, approximately 6.5x10 8 one or more Tmem, approximately 7.0x10 8 one or more Tmem, approximately 7.5x10 8 one or more Tmem, approximately 8.0x10 8 one or more Tmem, approximately 8.5x10 8 one or more Tmem, approximately 9.0x10 8 one or more Tmem, approximately 9.5x10 8 one or more Tmem, approximately 1.0x10 9 one or more Tmem, approximately 1.5x10 9 one or more Tmem, approximately 2.0x10 9 one or more Tmem, approximately 2.5x10 9 one or more Tmem, approximately 3.0x10 9 one or more Tmem, approximately 3.5x10 9 one or more Tmem, approximately 4.0x10 9 one or more Tmem, approximately 4.5x10 9 one or more Tmem, approximately 5.0x10 9 one or more Tmem, approximately 5.5x10 9 one or more Tmem, approximately 6.0x10 9 one or more Tmem, approximately 6.5x10 9 one or more Tmem, approximately 7.0x10 9 one or more Tmem, approximately 7.5x10 9 one or more Tmem, approximately 8.0x10 9 one or more Tmem, approximately 8.5x10 9 one or more Tmem, approximately 9.0x10 9 one or more Tmem, approximately 9.5x10 9 one or more Tmem, approximately 1.0x10 10 one or more Tmem or approximately 1.5x10 10 one or more Tmem; and / or e) The dose of the fresh Tregs includes the following doses: approximately 1.0x10 5 or more fresh Tregs per kg of body weight of the human subject receiving the product, approximately 2.0x10 5 or more fresh Tregs per kg of body weight of the human subject receiving the product, approximately 3.0x10 5 or more fresh Tregs per kg of body weight of the human subject receiving the product, approximately 4.0x10 5 or more fresh Tregs per kg of body weight of the human subject receiving the product, approximately 5.0x10 5 or more fresh Tregs per kg of body weight of the human subject receiving the product, approximately 6.0x10 5 or more fresh Tregs per kg of body weight of the human subject receiving the product, approximately 7.0x10 5 or more fresh Tregs per kg of body weight of the human subject receiving the product, approximately 8.0x10 5 or more fresh Tregs per kg of body weight of the human subject receiving the product, approximately 9.0x10 5 or more fresh Tregs per kg of body weight of the human subject receiving the product, approximately 1.0x10 6 or more fresh Tregs per kg of body weight of the human subject receiving the product, approximately 1.5x10 6 or more fresh Tregs per kg of body weight of the human subject receiving the product, approximately 2.0x10 6 or more fresh Tregs per kg of body weight of the human subject receiving the product, approximately 2.5x10 6 or more fresh Tregs per kg of body weight of the human subject receiving the product, approximately 3.0x10 6 or more fresh Tregs per kg of body weight of the human subject receiving the product, approximately 3.5x10 6 or more fresh Tregs per kg of body weight of the human subject receiving the product, approximately 4.0x10 6 or more fresh Tregs per kg of body weight of the human subject receiving the product, approximately 4.5x10 6 or more fresh Tregs per kg of body weight of the human subject receiving the product, approximately 5.0x10 6 One or more fresh Tregs, approximately 5.5x10 per kilogram of body weight of the human subject receiving the product 6 One or more fresh Tregs, approximately 6.0x10 per kilogram of body weight of the human subject receiving the product 6 One or more fresh Tregs, approximately 6.5x10 per kilogram of body weight of the human subject receiving the product 6 One or more fresh Tregs, approximately 7.0x10 per kilogram of body weight of the human subject receiving the product 6 One or more fresh Tregs, approximately 7.5x10 per kilogram of body weight of the human subject receiving the product 6 One or more fresh Tregs, approximately 8.0x10 per kilogram of body weight of the human subject receiving the product 6 One or more fresh Tregs, approximately 8.5x10 per kilogram of body weight of the human subject receiving the product 6 One or more fresh Tregs, approximately 9.0x10 per kilogram of body weight of the human subject receiving the product 6 One or more fresh Tregs, approximately 9.5x10 per kilogram of body weight of the human subject receiving the product 6 One or more fresh Tregs, approximately 1.0x10 per kilogram of body weight of the human subject receiving the product 7 One or more fresh Tregs, approximately 1.5x10 per kilogram of body weight of the human subject receiving the product 7 One or more fresh Tregs or approximately 2.0x10 per kilogram of body weight of the human subject receiving the product 7 One or more fresh Tregs; and / or f) The dose of the fresh Tregs comprises the following total doses: approximately 5.0x10 5 or more fresh Tregs, approximately 6.0x10 5 or more fresh Tregs, approximately 7.0x10 5 or more fresh Tregs, approximately 8.0x10 5 or more fresh Tregs, approximately 9.0x10 5 or more fresh Tregs, approximately 1.0x10 6 or more fresh Tregs, approximately 1.5x10 6 or more fresh Tregs, approximately 2.0x10 6 or more fresh Tregs, approximately 2.5x10 6 or more fresh Tregs, approximately 3.0x10 6 or more fresh Tregs, approximately 3.5x10 6 or more fresh Tregs, approximately 4.0x10 6 or more fresh Tregs, approximately 4.5x10 6 or more fresh Tregs, approximately 5.0x10 6 or more fresh Tregs, approximately 5.5x10 6 or more fresh Tregs, approximately 6.0x10 6 or more fresh Tregs, approximately 6.5x10 6 or more fresh Tregs, approximately 7.0x10 6 or more fresh Tregs, approximately 7.5x10 6 or more fresh Tregs, approximately 8.0x10 6 or more fresh Tregs, approximately 8.5x10 6 or more fresh Tregs, approximately 9.0x10 6 or more fresh Tregs, approximately 9.5x10 6 or more fresh Tregs, approximately 1.0x10 7 or more fresh Tregs, approximately 1.5x10 7 or more fresh Tregs, approximately 2.0x10 7 or more fresh Tregs, approximately 2.5x10 7 or more fresh Tregs, approximately 3.0x10 7 or more fresh Tregs, approximately 3.5x10 7 or more fresh Tregs, approximately 4.0x10 7 One or more fresh Tregs, approximately 4.5x10 7 One or more fresh Tregs, approximately 5.0x10 7 One or more fresh Tregs, approximately 5.5x10 7 One or more fresh Tregs, approximately 6.0x10 7 One or more fresh Tregs, approximately 6.5x10 7 One or more fresh Tregs, approximately 7.0x10 7 One or more fresh Tregs, approximately 7.5x10 7 One or more fresh Tregs, approximately 8.0x10 7 One or more fresh Tregs, approximately 8.5x10 7 One or more fresh Tregs, approximately 9.0x10 7 One or more fresh Tregs, approximately 9.5x10 7 One or more fresh Tregs, approximately 1.0x10 8 One or more fresh Tregs, approximately 1.5x10 8 One or more fresh Tregs, approximately 2.0x10 8 One or more fresh Tregs, approximately 2.5x10 8 One or more fresh Tregs, approximately 3.0x10 8 One or more fresh Tregs, approximately 3.5x10 8 One or more fresh Tregs, approximately 4.0x10 8 One or more fresh Tregs, approximately 4.5x10 8 One or more fresh Tregs, approximately 5.0x10 8 One or more fresh Tregs, approximately 5.5x10 8 One or more fresh Tregs, approximately 6.0x10 8 One or more fresh Tregs, approximately 6.5x10 8 One or more fresh Tregs, approximately 7.0x10 8 One or more fresh Tregs, approximately 7.5x10 8 One or more fresh Tregs, approximately 8.0x10 8 One or more fresh Tregs, approximately 8.5x10 8 One or more fresh Tregs, approximately 9.0x10 8 One or more fresh Tregs, approximately 9.5x10 8 One or more fresh Tregs, approximately 1.0x10 9 one or more fresh Tregs, approximately 1.5x10 9 one or more fresh Tregs, approximately 2.0x10 9 one or more fresh Tregs, approximately 2.5x10 9 one or more fresh Tregs or approximately 3.0x10 9 one or more fresh Tregs; and / or g) The cell therapy product contains less than approximately 5.0 x 10 5 Tcons per kilogram of body weight of the human subject receiving the product, less than approximately 4.5 x 10 5 Tcons per kilogram of body weight of the human subject receiving the product, less than approximately 4.0 x 10 5 Tcons per kilogram of body weight of the human subject receiving the product, less than approximately 3.5 x 10 5 Tcons per kilogram of body weight of the human subject receiving the product, less than approximately 3.0 x 10 5 Tcons per kilogram of body weight of the human subject receiving the product, less than approximately 2.5 x 10 5 Tcons per kilogram of body weight of the human subject receiving the product, less than approximately 2.0 x 10 5 Tcons per kilogram of body weight of the human subject receiving the product, less than approximately 1.5 x 10 5 Tcons per kilogram of body weight of the human subject receiving the product, less than approximately 1.0 x 10 5 Tcons per kilogram of body weight of the human subject receiving the product, less than approximately 9.5 x 10 4 Tcons per kilogram of body weight of the human subject receiving the product, less than approximately 9.0 x 10 4 Tcons per kilogram of body weight of the human subject receiving the product, less than approximately 8.5 x 10 4 Tcons per kilogram of body weight of the human subject receiving the product, less than approximately 8.0 x 10 4 Tcons per kilogram of body weight of the human subject receiving the product, less than approximately 7.5 x 10 4 Tcons per kilogram of body weight of the human subject receiving the product, less than approximately 7.0 x 10 4 Tcons per kilogram of body weight of the human subject receiving the product, less than approximately 6.5 x 10 4 Tcons per kilogram of body weight of the human subject receiving the product, less than approximately 6.0 x 10 4 Tcons per kilogram of body weight of the human subject receiving the product, less than approximately 5.5 x 10 4 Tcons per kilogram of body weight of the human subject receiving the product, less than approximately 5.0 x 10 4 Tcons per kilogram of body weight of the human subject receiving the product, less than approximately 4.5 x 10 4 Tcons, less than about 4.0x10 per kg of body weight of the human subject receiving the product 4 Tcons, less than about 3.5x10 per kg of body weight of the human subject receiving the product 4 Tcons, less than about 3.0x10 per kg of body weight of the human subject receiving the product 4 Tcons, less than about 2.5x10 per kg of body weight of the human subject receiving the product 4 Tcons, less than about 2.0x10 per kg of body weight of the human subject receiving the product 4 Tcons, less than about 1.5x10 per kg of body weight of the human subject receiving the product 4 Tcons, less than about 1.0x10 per kg of body weight of the human subject receiving the product 4 Tcons, less than about 9.5x10 per kg of body weight of the human subject receiving the product 3 Tcons, less than about 9.0x10 per kg of body weight of the human subject receiving the product 3 Tcons, less than about 8.5x10 per kg of body weight of the human subject receiving the product 3 Tcons, less than about 8.0x10 per kg of body weight of the human subject receiving the product 3 Tcons, less than about 7.5x10 per kg of body weight of the human subject receiving the product 3 Tcons, less than about 7.0x10 per kg of body weight of the human subject receiving the product 3 Tcons, less than about 6.5x10 per kg of body weight of the human subject receiving the product 3 Tcons, less than about 6.0x10 per kg of body weight of the human subject receiving the product 3 Tcons, less than about 5.5x10 per kg of body weight of the human subject receiving the product 3 Tcons, less than about 5.0x10 per kg of body weight of the human subject receiving the product 3 Tcons, less than about 4.5x10 per kg of body weight of the human subject receiving the product 3 Tcons, less than about 4.0x10 per kg of body weight of the human subject receiving the product 3 Tcons, less than about 3.5x10 per kg of body weight of the human subject receiving the product 3 Tcons, less than about 3.0x10 per kilogram of body weight of the human subject receiving the product 3 Tcons, less than about 2.5x10 per kilogram of body weight of the human subject receiving the product 3 Tcons, less than about 2.0x10 per kilogram of body weight of the human subject receiving the product 3 Tcons, less than about 1.5x10 per kilogram of body weight of the human subject receiving the product 3 Tcons or less than about 1.0x10 per kilogram of body weight of the human subject receiving the product 3 Tcons; and / or h) The cell therapy product contains less than approximately 6.0x10 7 total Tcons, less than approximately 5.5x10 7 total Tcons, less than approximately 5.0x10 7 total Tcons, less than approximately 4.5x10 7 total Tcons, less than approximately 4.0x10 7 total Tcons, less than approximately 3.5x10 7 total Tcons, less than approximately 3.0x10 7 total Tcons, less than approximately 2.5x10 7 total Tcons, less than approximately 2.0x10 7 total Tcons, less than approximately 1.5x10 7 total Tcons, less than approximately 1.0x10 7 total Tcons, less than approximately 9.5x10 6 total Tcons, less than approximately 9.0x10 6 total Tcons, less than approximately 8.5x10 6 total Tcons, less than approximately 8.0x10 6 total Tcons, less than approximately 7.5x10 6 total Tcons, less than approximately 7.0x10 6 total Tcons, less than approximately 6.5x10 6 total Tcons, less than approximately 6.0x10 6 total Tcons, less than approximately 5.5x10 6 total Tcons, less than approximately 5.0x10 6 total Tcons, less than approximately 4.5x10 6 total Tcons, less than approximately 4.0x10 6 total Tcons, less than approximately 3.5x10 6 total Tcons, less than approximately 3.0x10 6 total Tcons, less than approximately 2.5x10 6 total Tcons, less than approximately 2.0x10 6 total Tcons, less than approximately 1.5x10 6 total Tcons or less than approximately 1.0x10 6 total Tcons.

3. The cell therapy product according to claim 1 or claim 2, wherein: a) The population consisting of isolated CD45 + cells is formulated in a volume ranging from about 5 mL to about 1 L; and / or b) the population consisting of isolated CD45 + cells is formulated in a volume of: 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 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 ranges from about 6.8 to about 7.6; and / or d) The excipient comprises a transfer buffer, optionally wherein the transfer buffer comprises from about 120 mEq to about 160 mEq of sodium, and / or the transfer buffer has a total osmolality of from about 270 mOsmol / L to about 320 mOsmol / L, optionally wherein the transfer buffer is selected from the group consisting of phosphate buffered saline (PBS), human serum, PlasmaLyte, Normosol-R, and any combination thereof, optionally wherein the transfer buffer further comprises from about 0.1% by volume to about 10% by volume of a human carrier protein, optionally wherein 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 population consisting of isolated CD45 + cells is formulated in a single-dose transfer bag, optionally wherein the single-dose transfer bag is a polyvinyl chloride (PVC) transfer bag or an ethylene vinyl acetate (EVA) transfer bag; and / or f) the population consisting of isolated CD45 + cells is enriched in HSPC, Tmem, and Treg; and / or g) the population consisting of the isolated CD45 + cells has a ratio of Tcon to HSPC of 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 1:6,500, 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, 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 population consisting of the isolated CD45 + cells has a ratio of Tcon to Tmem of 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 1:6,500, 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 population consisting of isolated CD45 + cells has a ratio of Tcon to 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 1:11, 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 1:9,000, 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 population consisting of isolated CD45 + cells has a ratio of HSPC to Tmem of from about 500:1 to about 1:1,000; and / or k) the population consisting of isolated CD45 + cells has a ratio of HSPC to Treg of from about 100:1 to about 1:30; and / or l) The population consisting of isolated CD45 + cells has a ratio of Tmem to Treg of from about 2000:1 to about 1:10; and / or m) the population consisting of isolated CD45 + cells further comprises a population enriched in TCR Vα24Jα18 + CD127 + invariant natural killer T cells (iNKT), optionally wherein the population consisting of isolated CD45 + cells comprises a dose of from about 5.0×10 2 to about 2.0×10 6 iNKT per kg body weight of the human subject receiving the product, or a total dose of from about 2.0x10 3 to about 4.0x10 8 iNKT, optionally wherein the dose of iNKT comprises the following doses: from about 5.0x10 2 or more iNKT per kg body weight of the human subject receiving the product, from about 6.0x10 2 or more iNKT per kg body weight of the human subject receiving the product, from about 7.0x10 2 or more iNKT per kg body weight of the human subject receiving the product, from about 8.0x10 2 or more iNKT per kg body weight of the human subject receiving the product, from about 9.0x10 2 or more iNKT per kg body weight of the human subject receiving the product, from about 1.0x10 3 or more iNKT per kg body weight of the human subject receiving the product, from about 2.0x10 3 or more iNKT per kg body weight of the human subject receiving the product, from about 3.0x10 3 or more iNKT per kg body weight of the human subject receiving the product, from about 4.0x10 3 or more iNKT per kg body weight of the human subject receiving the product, from about 5.0x10 3 or more iNKT per kg body weight of the human subject receiving the product, from about 6.0x10 3 or more iNKT per kg body weight of the human subject receiving the product, from about 7.0x10 3 or more iNKT per kg body weight of the human subject receiving the product, from about 8.0x10 3 or more iNKT per kg body weight of the human subject receiving the product, from about 9.0x10 3 one or more iNKTs, approximately 1.0x10 per kg of body weight of the human subject receiving the product 4 one or more iNKTs, approximately 2.0x10 per kg of body weight of the human subject receiving the product 4 one or more iNKTs, approximately 3.0x10 per kg of body weight of the human subject receiving the product 4 one or more iNKTs, approximately 4.0x10 per kg of body weight of the human subject receiving the product 4 one or more iNKTs, approximately 5.0x10 per kg of body weight of the human subject receiving the product 4 one or more iNKTs, approximately 6.0x10 per kg of body weight of the human subject receiving the product 4 one or more iNKTs, approximately 7.0x10 per kg of body weight of the human subject receiving the product 4 one or more iNKTs, approximately 8.0x10 per kg of body weight of the human subject receiving the product 4 one or more iNKTs, approximately 9.0x10 per kg of body weight of the human subject receiving the product 4 one or more iNKTs, approximately 1.0x10 per kg of body weight of the human subject receiving the product 5 one or more iNKTs, approximately 2.0x10 per kg of body weight of the human subject receiving the product 5 one or more iNKTs, approximately 3.0x10 per kg of body weight of the human subject receiving the product 5 one or more iNKTs, approximately 4.0x10 per kg of body weight of the human subject receiving the product 5 one or more iNKTs, approximately 5.0x10 per kg of body weight of the human subject receiving the product 5 one or more iNKTs, approximately 6.0x10 per kg of body weight of the human subject receiving the product 5 one or more iNKTs, approximately 7.0x10 per kg of body weight of the human subject receiving the product 5 one or more iNKTs, approximately 8.0x10 per kg of body weight of the human subject receiving the product 5 one or more iNKTs, approximately 9.0x10 per kg of body weight of the human subject receiving the product 5 one or more iNKTs, approximately 1.0x10 per kg of body weight of the human subject receiving the product 6 One or more iNKTs, about 1.5x10 per kilogram of body weight of the human subject receiving the product 6 One or more iNKTs or about 2.0x10 per kilogram of body weight of the human subject receiving the product 6 One or more iNKTs, optionally wherein the dose of the iNKTs comprises the following total doses: about 2.0x10 3 One or more iNKTs, about 3.0x10 3 One or more iNKTs, about 4.0x10 3 One or more iNKTs, about 5.0x10 3 One or more iNKTs, about 6.0x10 3 One or more iNKTs, about 7.0x10 3 One or more iNKTs, about 8.0x10 3 One or more iNKTs, about 9.0x10 3 One or more iNKTs, about 1.0x10 4 One or more iNKTs, about 2.0x10 4 One or more iNKTs, about 3.0x10 4 One or more iNKTs, about 4.0x10 4 One or more iNKTs, about 5.0x10 4 One or more iNKTs, about 6.0x10 4 One or more iNKTs, about 7.0x10 4 One or more iNKTs, about 8.0x10 4 One or more iNKTs, about 9.0x10 4 One or more iNKTs, about 1.0x10 5 One or more iNKTs, about 2.0x10 5 One or more iNKTs, about 3.0x10 5 One or more iNKTs, about 4.0x10 5 One or more iNKTs, about 5.0x10 5 One or more iNKTs, about 6.0x10 5 One or more iNKTs, about 7.0x10 5 One or more iNKTs, about 8.0x10 5 One or more iNKTs, about 9.0x10 5 One or more iNKTs, about 1.0x10 6 One or more iNKTs, about 1.5x10 6 one or more iNKTs, approximately 2.0x10 6 one or more iNKTs, approximately 2.5x10 6 one or more iNKTs, approximately 3.0x10 6 one or more iNKTs, approximately 3.5x10 6 one or more iNKTs, approximately 4.0x10 6 one or more iNKTs, approximately 4.5x10 6 one or more iNKTs, approximately 5.0x10 6 one or more iNKTs, approximately 5.5x10 6 one or more iNKTs, approximately 6.0x10 6 one or more iNKTs, approximately 6.5x10 6 one or more iNKTs, approximately 7.0x10 6 one or more iNKTs, approximately 7.5x10 6 one or more iNKTs, approximately 8.0x10 6 one or more iNKTs, approximately 8.5x10 6 one or more iNKTs, approximately 9.0x10 6 one or more iNKTs, approximately 9.5x10 6 one or more iNKTs, approximately 1.0x10 7 one or more iNKTs, approximately 1.5x10 7 one or more iNKTs, approximately 2.0x10 7 one or more iNKTs, approximately 2.5x10 7 one or more iNKTs, approximately 3.0x10 7 one or more iNKTs, approximately 3.5x10 7 one or more iNKTs, approximately 4.0x10 7 one or more iNKTs, approximately 4.5x10 7 one or more iNKTs, approximately 5.0x10 7 one or more iNKTs, approximately 5.5x10 7 one or more iNKTs, approximately 6.0x10 7 one or more iNKTs, approximately 6.5x10 7 one or more iNKTs, approximately 7.0x10 7 one or more iNKTs, approximately 7.5x10 7 one or more iNKTs, approximately 8.0x10 7 one or more iNKTs, approximately 8.5x10 7 one or more iNKTs, about 9.0x10 7 one or more iNKTs, about 9.5x10 7 one or more iNKTs, about 1.0x10 8 one or more iNKTs, about 1.5x10 8 one or more iNKTs, about 2.0x10 8 one or more iNKTs, about 2.5x10 8 one or more iNKTs, about 3.0x10 8 one or more iNKTs, about 3.5x10 8 one or more iNKTs or about 4.0x10 8 one or more iNKTs, optionally wherein the population consisting of isolated CD45 + cells has a ratio of HSPC to iNKT of about 1:2 to about 500,000:1, optionally wherein the population consisting of isolated CD45 + cells has a ratio of iNKT to Tcon 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, optionally wherein the population consisting of isolated CD45 + cells has a ratio of iNKT to Tmem of about 5:1 to about 1:1,000,000, optionally wherein the 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 includes a population composed of central memory T cells (T CM ), a population composed of effector memory T cells (T EM ), a population composed of stem cell central memory T cells (T SCM ), or any combination thereof, optionally wherein the T CM is CD4 + CD45RO + or CD8 + CD45RO + , and / or the T CM is CD45RA - , CD62L + , CCR7 + , or any combination thereof, optionally wherein the T EM is CD4 + , CD45RO + , CD45RA - , CD62L - , CCR7 - , or any combination thereof, optionally wherein the T 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 consisting of naive Treg cells, a population consisting of memory Treg cells, or a population consisting of naive Treg cells and memory Treg cells, optionally wherein the naive Treg cells are CD4 + CD25 + CD127 dim FoxP3 + CD45RA + CD45RO - , optionally wherein the dose of the Tregs comprises from about 2.0x10 5 to about 5.0x10 8 naive Treg cells per kilogram of body weight of the human subject receiving the product or a total dose of from about 8.0x10 5 to about 1.0x10 11 naive Treg cells; optionally wherein the population consisting of isolated CD45 + cells has a ratio of HSPC to naive Tregs of from about 1:500 to about 100:1, optionally wherein the population consisting of isolated CD45 + cells has a ratio of Tmem to naive Tregs of from about 3:1 to about 1:10, optionally wherein the population consisting of isolated CD45 + cells has a ratio of Tcon to naive Tregs 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, optionally wherein the memory Treg cells are CD4 + CD25 + CD127 dim FoxP3 + CD45RA - CD45RO + , optionally wherein the dose of the Tregs comprises from about 5.0x10 4 to about 5.0x10 8 memory Treg cells per kilogram of body weight of the human subject receiving the product or a total dose of from about 2.0x10 5 to about 1.0x10 11 memory Treg cells, optionally wherein the population consisting of isolated CD45 + cells has a ratio of HSPC to memory Tregs of from about 1:500 to about 10,000:1, optionally wherein the population consisting of isolated CD45 + The ratio of Tmem to memory Treg in the population of cells is from about 27:1 to about 9:10, optionally wherein the isolated CD45 + The ratio of Tcon to memory Treg in 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 1:20, 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 the Tcon is CD25 - , CD127 + or CD25 - CD127 + , and / or the Tcon is TCRα + TCRβ + CD45RA + CD45RO - CD25 - CD95 - IL-2Rβ - CD127 + ; and / or t) the population consisting of isolated CD45 + cells contains less than about 5 EU to less than about 0.5 EU of endotoxin per mL of the preparation; and / or u) The body weight of the human subject receiving the product is the actual body weight, or the body weight of the human subject receiving the product is the ideal body weight.

4. The cell therapy product according to any one of claims 1 to 3, wherein the product further comprises a pharmaceutical composition comprising one or more doses of a graft-versus-host disease (GVHD) prophylactic agent, optionally wherein the GVHD prophylactic agent is tacrolimus, optionally wherein one or more doses of tacrolimus are provided to maintain a trough blood level of from about 5 ng / mL to about 10 ng / mL in the human subject receiving the product, optionally wherein the pharmaceutical composition comprises from about 0.01 mg to about 0.50 mg per kilogram of body weight of the human subject receiving the product, of tacrolimus, administered twice daily, optionally wherein after administration of the population of isolated CD45 + cells, the tacrolimus is dosed in an amount to maintain a target blood level of from about 1 ng / mL to about 10 ng / mL in the human subject receiving the product or is dosed in an amount to maintain the target blood level in the human subject receiving the product for about 20 days or longer, about 25 days or longer, about 30 days or longer, about 35 days or longer, about 40 days or longer, about 45 days or longer, about 50 days or longer, about 55 days or longer, about 60 days or longer, about 65 days or longer, about 70 days or longer, about 75 days or longer, about 80 days or longer, about 85 days or longer, about 90 days or longer, about 95 days or longer, about 100 days or longer, about 110 days or longer, about 120 days or longer, about 130 days or longer, about 140 days or longer or about 150 days.

5. The cell therapy product according to any one of claims 1 to 4, wherein: a) The HSPC, the Tmem, the Treg, or any combination thereof is obtained from an allogeneic donor HLA-matched to the human subject receiving the product, and / or the population consisting of isolated CD45 + cells is from an allogeneic donor HLA-matched to the human subject receiving the product; or b) wherein the HSPC, the Tmem, the Treg, or any combination thereof is obtained from an allogeneic donor having at least one HLA mismatch relative to the human subject receiving the product, and / or the population consisting of isolated CD45 + cells is from an allogeneic donor having at least one HLA mismatch relative to the human subject receiving the product, optionally wherein 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, optionally wherein the cells having at least one HLA mismatch are from a donor that is 6 / 8 HLA mismatched relative to the human subject receiving the product, or the cells having at least one HLA mismatch are from a donor that is 7 / 8 HLA mismatched relative to the human subject receiving the product, optionally wherein the cells having at least one HLA mismatch are from a donor that is 7 / 8 HLA mismatched relative to the human subject receiving the product, optionally wherein the donor that is 7 / 8 HLA mismatched relative to the human subject receiving the product has a mismatch in HLA-A, optionally wherein the donor that is 7 / 8 HLA mismatched relative to the human subject receiving the product has a mismatch in HLA-B, optionally wherein the donor that is 7 / 8 HLA mismatched relative to the human subject receiving the product has a mismatch in HLA-C, optionally wherein the donor that is 7 / 8 HLA mismatched relative to the human subject receiving the product has a mismatch in HLA-DRB1, optionally wherein the donor having the 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 while the human subject receiving the product is heterozygous for the HLA allele, optionally wherein the donor having the 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 while the human subject receiving the product is homozygous for the HLA allele, optionally wherein the donor having the at least one HLA mismatch relative 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 HSPC, the Tmem, the Treg, or any combination thereof is obtained from a donor who is haploidentical relative to the human subject receiving the product, or the population consisting of isolated CD45 + cells is from a donor who is haploidentical relative to the human subject receiving the product, Optionally wherein 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.

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

7. A method for treating the following human subjects: a) Suffering from or suspected of suffering from acute leukemia in a complete remission state, the method comprising administering to the human subject a cell therapy product comprising a population of cells consisting of isolated CD45 + cells, wherein the population of cells consisting of isolated CD45 + cells comprises an enriched population of CD34 + hematopoietic stem and progenitor cells (HSPCs), an enriched population of CD45RA - memory T cells (Tmem), and an enriched population of fresh CD4 + CD25 + CD127 dim regulatory T cells (Treg), and wherein the population of cells consisting of isolated CD45 + cells has depleted naive conventional CD3 + CD25 - CD45RA + T cells (Tcon) to comprise less than about 5.0x10 5 naive conventional CD3 + CD25 - CD45RA + T cells (Tcon) per kilogram of body weight of the human subject receiving the product, less than about 6.0x10 7 total naive conventional CD3 + CD25 - CD45RA +T cells (Tcon) or less than about 1.0x10 6 total naive conventional CD3 + CD25 - CD45RA + T cells (Tcon), optionally wherein the human subject has a blastic burden of about 5% or less in their bone marrow, optionally wherein there are no circulating blasts and / or blasts with Auer rods in the human subject, optionally wherein there is no extramedullary disease in the human subject, optionally wherein the absolute neutrophil count (ANC) of the human subject is about 1.0x10 9 / L or higher, optionally wherein the platelet count of the human subject is about 1.0x10 11 / L or higher, optionally wherein the human subject is red blood cell transfusion independent, optionally wherein the acute leukemia is in complete remission and hematologic incomplete recovery, optionally wherein the human subject has residual neutropenia, optionally wherein the absolute neutrophil count (ANC) of the human subject is about 1.0x10 9 / L or lower, optionally wherein the human subject has residual thrombocytopenia, optionally wherein the platelet count of the human subject is about 1.0x10 11 / L or lower; or b) having or suspected of having active acute leukemia, the method comprising administering to the human subject a cell therapy product comprising a population of isolated CD45 + cells, wherein the population of isolated CD45 + cells comprises an enriched population of CD34 + hematopoietic stem and progenitor cells (HSPCs), an enriched population of CD45RA - memory T cells (Tmem) and an enriched population of freshly isolated CD4 + CD25 + CD127 dim regulatory T cells (Tregs), and wherein the population of isolated CD45 + cells has been depleted of naive conventional CD3 + CD25 - CD45RA + T cells (Tcon) to comprise less than about 5.0x10 5 naive conventional CD3 + CD25 - CD45RA +T cells (Tcon), fewer than approximately 6.0x10 7 total naive conventional CD3 + CD25 - CD45RA + T cells (Tcon) or fewer than approximately 1.0x10 6 total naive conventional CD3 + CD25 - CD45RA + T cells (Tcon), optionally wherein the human subject has approximately 10% or less bone marrow blasts infiltration, optionally wherein the acute leukemia is acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and / or mixed phenotype acute leukemia (MPAL); or c) having or suspected of having chronic myelogenous leukemia (CML), the method comprising administering to the human subject a cell therapy product comprising a population of cells consisting of isolated CD45 + cells, wherein the population of cells consisting of isolated CD45 + cells comprises a population enriched in cells consisting of CD34 + hematopoietic stem and progenitor cells (HSPCs), a population enriched in cells consisting of CD45RA - memory T cells (Tmem), and a population enriched in cells consisting of fresh CD4 + CD25 + CD127 dim regulatory T cells (Treg), and wherein the population of cells consisting of isolated CD45 + cells has been depleted of naive conventional CD3 + CD25 - CD45RA + T cells (Tcon) to comprise fewer than approximately 5.0x10 5 naive conventional CD3 + CD25 - CD45RA + T cells (Tcon), fewer than approximately 6.0x10 7 total naive conventional CD3 + CD25 - CD45RA + T cells (Tcon) or fewer than approximately 1.0x10 6 total naive conventional CD3 + CD25 - CD45RA +T cells (Tcon), optionally wherein the human subject is in myeloid blast crisis and / or lymphoblastic blast crisis, optionally wherein the blast crisis is in a state of complete remission, optionally wherein the blast crisis is in a state of complete remission and incomplete hematological recovery, optionally wherein the CML is in the accelerated phase or the CML is in the chronic phase, optionally wherein the chronic phase CML is resistant or intolerant to one or more first-generation or second-generation tyrosine kinase inhibitors (TKIs); or d) 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 comprising a population of cells consisting of isolated CD45 + cells, wherein the population of cells consisting of isolated CD45 + cells comprises an enriched population of CD34 + hematopoietic stem and progenitor cells (HSPCs), an enriched population of CD45RA - memory T cells (Tmem), and an enriched population of freshly isolated CD4 + CD25 + CD127 dim regulatory T cells (Treg), and wherein the population of cells consisting of isolated CD45 + cells has been depleted of naive conventional CD3 + CD25 - CD45RA + T cells (Tcon) to comprise less than about 5.0 x 10 5 naive conventional CD3 + CD25 - CD45RA + T cells (Tcon), less than about 6.0 x 10 7 total naive conventional CD3 + CD25 - CD45RA + T cells (Tcon), or less than about 1.0 x 10 6 total naive conventional CD3 + CD25 - CD45RA + T cells (Tcon), optionally wherein the human subject has a blast load of about 10% or less in their bone marrow; or e) having or suspected of having myelofibrosis, the method comprising administering to the human subject a cell therapy product comprising a population of cells consisting of isolated CD45 + cells, wherein the population of cells consisting of isolated CD45 +A population of cells comprises an enriched population of CD34 + hematopoietic stem and progenitor cells (HSPCs), an enriched population of CD45RA - memory T cells (Tmem), and an enriched population of fresh CD4 + CD25 + CD127 dim regulatory T cells (Tregs), and wherein the population of isolated CD45 + cells has been depleted of naive conventional CD3 + CD25 - CD45RA + T cells (Tcon) to comprise less than about 5.0 x 10 5 naive conventional CD3 + CD25 - CD45RA + T cells (Tcon) per kilogram of body weight of the human subject receiving the product, less than about 6.0 x 10 7 total naive conventional CD3 + CD25 - CD45RA + T cells (Tcon), or less than about 1.0 x 10 6 total naive conventional CD3 + CD25 - CD45RA + T cells (Tcon), optionally wherein the myelofibrosis is eligible for standard myeloablative allogeneic hematopoietic stem cell transplantation (alloHSCT), optionally wherein the myelofibrosis is intermediate-risk-2 myelofibrosis or high-risk myelofibrosis, optionally wherein the myelofibrosis is intermediate-risk-1 myelofibrosis associated with high symptom burden, low platelet count, and / or complex cytogenetics.

8. The method according to claim 7, wherein: 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 at a dose ranging from about 0.01 mg per kilogram of body weight of the human subject twice daily to 0.50 mg per kilogram of body weight of the human subject, optionally wherein after administering a third population consisting of CD45 + cells, the tacrolimus is dosed in an amount to maintain a target blood level of about 1 ng / mL to about 10 ng / mL in the human subject or is dosed in an amount to maintain the target blood level in the human subject for about 20 days or longer, about 25 days or longer, about 30 days or longer, about 35 days or longer, about 40 days or longer, about 55 days or longer, about 50 days or longer, about 55 days or longer, about 60 days or longer, about 65 days or longer, about 770 days or longer, about 75 days or longer, about 80 days or longer, about 85 days or longer, about 90 days or longer, about 95 days or longer, about 100 days or longer, about 110 days or longer, about 120 days or longer, about 130 days or longer, about 140 days or longer or about 150 days, optionally wherein the administration of the tacrolimus begins about 12 hours to about 24 hours after administering the cell therapy product, optionally wherein the administration of the tacrolimus is tapered beginning about 90 days after the initial administration of the tacrolimus; and / or b) said administration comprises infusing said population consisting of isolated CD45 + cells into said human subject; and / or c) the population consisting of isolated CD45 + cells comprises from about 1.0 x 10 5 to about 1.0 x 10 8 HSPCs per kilogram of body weight of the human subject; and / or 5 from about 5.0 x 10 10 to about 1.5 x 10 HSPCs; and / or d) the population consisting of the isolated CD45 + cells contains about 1.0x10 5 or more HSPCs per kilogram of the body weight of the human subject, about 2.0x10 5 or more HSPCs per kilogram of the body weight of the human subject, about 3.0x10 5 or more HSPCs per kilogram of the body weight of the human subject, about 4.0x10 5 or more HSPCs per kilogram of the body weight of the human subject, about 5.0x10 5 or more HSPCs per kilogram of the body weight of the human subject, about 6.0x10 5 or more HSPCs per kilogram of the body weight of the human subject, about 7.0x10 5 or more HSPCs per kilogram of the body weight of the human subject, about 8.0x10 5 or more HSPCs per kilogram of the body weight of the human subject, about 9.0x10 5 or more HSPCs per kilogram of the body weight of the human subject, about 1.0x10 6 or more HSPCs per kilogram of the body weight of the human subject, about 1.5x10 6 or more HSPCs per kilogram of the body weight of the human subject, about 2.0x10 6 or more HSPCs per kilogram of the body weight of the human subject, about 2.5x10 6 or more HSPCs per kilogram of the body weight of the human subject, about 3.0x10 6 or more HSPCs per kilogram of the body weight of the human subject, about 3.5x10 6 or more HSPCs per kilogram of the body weight of the human subject, about 4.0x10 6 or more HSPCs per kilogram of the body weight of the human subject, about 4.5x10 6 or more HSPCs per kilogram of the body weight of the human subject, about 5.0x10 6 or more HSPCs per kilogram of the body weight of the human subject, about 5.5x10 6 or more HSPCs per kilogram of the body weight of the human subject, about 6.0x10 6 or more HSPCs per kilogram of the body weight of the human subject, about 6.5x10 6 or more HSPCs per kilogram of the body weight of the human subject, about 7.0x10 6 one or more HSPCs, about 7.5x10 per kilogram of the body weight of the human subject 6 one or more HSPCs, about 8.0x10 per kilogram of the body weight of the human subject 6 one or more HSPCs, about 8.5x10 per kilogram of the body weight of the human subject 6 one or more HSPCs, about 9.0x10 per kilogram of the body weight of the human subject 6 one or more HSPCs, about 9.5x10 per kilogram of the body weight of the human subject 6 one or more HSPCs, about 1.0x10 per kilogram of the body weight of the human subject 7 one or more HSPCs, about 1.5x10 per kilogram of the body weight of the human subject 7 one or more HSPCs, about 2.0x10 per kilogram of the body weight of the human subject 7 one or more HSPCs, about 2.5x10 per kilogram of the body weight of the human subject 7 one or more HSPCs, about 3.0x10 per kilogram of the body weight of the human subject 7 one or more HSPCs, about 3.5x10 per kilogram of the body weight of the human subject 7 one or more HSPCs, about 4.0x10 per kilogram of the body weight of the human subject 7 one or more HSPCs, about 4.5x10 per kilogram of the body weight of the human subject 7 one or more HSPCs, about 5.0x10 per kilogram of the body weight of the human subject 7 one or more HSPCs, about 5.5x10 per kilogram of the body weight of the human subject 7 one or more HSPCs, about 6.0x10 per kilogram of the body weight of the human subject 7 one or more HSPCs, about 6.5x10 per kilogram of the body weight of the human subject 7 one or more HSPCs, about 7.0x10 per kilogram of the body weight of the human subject 7 one or more HSPCs, about 7.5x10 per kilogram of the body weight of the human subject 7 one or more HSPCs, about 8.0x10 per kilogram of the body weight of the human subject 7 one or more HSPCs, about 8.5x10 per kilogram of the body weight of the human subject 7 one or more HSPCs, about 9.0x10 per kilogram of the body weight of the human subject 7 one or more HSPCs, about 9.5x10 per kilogram of the body weight of the human subject 7 One or more HSPCs or about 1.0x10 per kilogram of the body weight of the human subject 8 One or more HSPCs; and / or e) The population consisting of the isolated CD45 + cells contains approximately 5.0 x 10 5 or more HSPCs, approximately 6.0 x 10 5 or more HSPCs, approximately 7.0 x 10 5 or more HSPCs, approximately 8.0 x 10 5 or more HSPCs, approximately 9.0 x 10 5 or more HSPCs, approximately 1.0 x 10 6 or more HSPCs, approximately 1.5 x 10 6 or more HSPCs, approximately 2.0 x 10 6 or more HSPCs, approximately 2.5 x 10 6 or more HSPCs, approximately 3.0 x 10 6 or more HSPCs, approximately 3.5 x 10 6 or more HSPCs, approximately 4.0 x 10 6 or more HSPCs, approximately 4.5 x 10 6 or more HSPCs, approximately 5.0 x 10 6 or more HSPCs, approximately 5.5 x 10 6 or more HSPCs, approximately 6.0 x 10 6 or more HSPCs, approximately 6.5 x 10 6 or more HSPCs, approximately 7.0 x 10 6 or more HSPCs, approximately 7.5 x 10 6 or more HSPCs, approximately 8.0 x 10 6 or more HSPCs, approximately 8.5 x 10 6 or more HSPCs, approximately 9.0 x 10 6 or more HSPCs, approximately 9.5 x 10 6 or more HSPCs, approximately 1.0 x 10 7 or more HSPCs, approximately 1.5 x 10 7 or more HSPCs, approximately 2.0 x 10 7 or more HSPCs, approximately 2.5 x 10 7 or more HSPCs, approximately 3.0 x 10 7 or more HSPCs, approximately 3.5 x 10 7 or more HSPCs, approximately 4.0 x 10 7 or more HSPCs, approximately 4.5 x 10 7 one or more HSPCs, approximately 5.0x10 7 one or more HSPCs, approximately 5.5x10 7 one or more HSPCs, approximately 6.0x10 7 one or more HSPCs, approximately 6.5x10 7 one or more HSPCs, approximately 7.0x10 7 one or more HSPCs, approximately 7.5x10 7 one or more HSPCs, approximately 8.0x10 7 one or more HSPCs, approximately 8.5x10 7 one or more HSPCs, approximately 9.0x10 7 one or more HSPCs, approximately 9.5x10 7 one or more HSPCs, approximately 1.0x10 8 one or more HSPCs, approximately 1.5x10 8 one or more HSPCs, approximately 2.0x10 8 one or more HSPCs, approximately 2.5x10 8 one or more HSPCs, approximately 3.0x10 8 one or more HSPCs, approximately 3.5x10 8 one or more HSPCs, approximately 4.0x10 8 one or more HSPCs, approximately 4.5x10 8 one or more HSPCs, approximately 5.0x10 8 one or more HSPCs, approximately 5.5x10 8 one or more HSPCs, approximately 6.0x10 8 one or more HSPCs, approximately 6.5x10 8 one or more HSPCs, approximately 7.0x10 8 one or more HSPCs, approximately 7.5x10 8 one or more HSPCs, approximately 8.0x10 8 one or more HSPCs, approximately 8.5x10 8 one or more HSPCs, approximately 9.0x10 8 one or more HSPCs, approximately 9.5x10 8 one or more HSPCs, approximately 1.0x10 9 one or more HSPCs, approximately 1.5x10 9 one or more HSPCs, approximately 2.0x10 9 one or more HSPCs, approximately 2.5x10 9 one or more HSPCs, approximately 3.0x10 9 one or more HSPCs, approximately 3.5x10 9 one or more HSPCs, approximately 4.0x10 9 one or more HSPCs, approximately 4.5x10 9 one or more HSPCs, approximately 5.0x10 9 one or more HSPCs, approximately 5.5x10 9 one or more HSPCs, approximately 6.0x10 9 one or more HSPCs, approximately 6.5x10 9 one or more HSPCs, approximately 7.0x10 9 one or more HSPCs, approximately 7.5x10 9 one or more HSPCs, approximately 8.0x10 9 one or more HSPCs, approximately 8.5x10 9 one or more HSPCs, approximately 9.0x10 9 one or more HSPCs, approximately 9.5x10 9 one or more HSPCs, approximately 1.0x10 10 one or more HSPCs or approximately 1.5x10 10 one or more HSPCs; and / or f) wherein the population consisting of the isolated CD45 + cells comprises from about 1.0 x 10 5 to about 1.0 x 10 8 Tmem per kilogram of body weight of the human subject receiving the product, about 5.0 x 10 5 to about 1.5 x 10 10 Tmem; and / or g) the population consisting of isolated CD45 + cells comprises about 1.0 x 10 5 or more Tmem per kg of body weight of the human subject who received the product, about 2.0 x 10 5 or more Tmem per kg of body weight of the human subject who received the product, about 3.0 x 10 5 or more Tmem per kg of body weight of the human subject who received the product, about 4.0 x 10 5 or more Tmem per kg of body weight of the human subject who received the product, about 5.0 x 10 5 or more Tmem per kg of body weight of the human subject who received the product, about 6.0 x 10 5 or more Tmem per kg of body weight of the human subject who received the product, about 7.0 x 10 5 or more Tmem per kg of body weight of the human subject who received the product, about 8.0 x 10 5 or more Tmem per kg of body weight of the human subject who received the product, about 9.0 x 10 5 or more Tmem per kg of body weight of the human subject who received the product, about 1.0 x 10 6 or more Tmem per kg of body weight of the human subject who received the product, about 1.5 x 10 6 or more Tmem per kg of body weight of the human subject who received the product, about 2.0 x 10 6 or more Tmem per kg of body weight of the human subject who received the product, about 2.5 x 10 6 or more Tmem per kg of body weight of the human subject who received the product, about 3.0 x 10 6 or more Tmem per kg of body weight of the human subject who received the product, about 3.5 x 10 6 or more Tmem per kg of body weight of the human subject who received the product, about 4.0 x 10 6 or more Tmem per kg of body weight of the human subject who received the product, about 4.5 x 10 6 or more Tmem per kg of body weight of the human subject who received the product, about 5.0 x 10 6 or more Tmem per kg of body weight of the human subject who received the product, about 5.5 x 10 6 one or more Tmem, about 6.0x10 per kilogram of body weight of the human subject receiving the product 6 one or more Tmem, about 6.5x10 per kilogram of body weight of the human subject receiving the product 6 one or more Tmem, about 7.0x10 per kilogram of body weight of the human subject receiving the product 6 one or more Tmem, about 7.5x10 per kilogram of body weight of the human subject receiving the product 6 one or more Tmem, about 8.0x10 per kilogram of body weight of the human subject receiving the product 6 one or more Tmem, about 8.5x10 per kilogram of body weight of the human subject receiving the product 6 one or more Tmem, about 9.0x10 per kilogram of body weight of the human subject receiving the product 6 one or more Tmem, about 9.5x10 per kilogram of body weight of the human subject receiving the product 6 one or more Tmem, about 1.0x10 per kilogram of body weight of the human subject receiving the product 7 one or more Tmem, about 1.5x10 per kilogram of body weight of the human subject receiving the product 7 one or more Tmem, about 2.0x10 per kilogram of body weight of the human subject receiving the product 7 one or more Tmem, about 2.5x10 per kilogram of body weight of the human subject receiving the product 7 one or more Tmem, about 3.0x10 per kilogram of body weight of the human subject receiving the product 7 one or more Tmem, about 3.5x10 per kilogram of body weight of the human subject receiving the product 7 one or more Tmem, about 4.0x10 per kilogram of body weight of the human subject receiving the product 7 one or more Tmem, about 4.5x10 per kilogram of body weight of the human subject receiving the product 7 one or more Tmem, about 5.0x10 per kilogram of body weight of the human subject receiving the product 7 one or more Tmem, about 5.5x10 per kilogram of body weight of the human subject receiving the product 7 one or more Tmem, about 6.0x10 per kilogram of body weight of the human subject receiving the product 7 one or more Tmem, about 6.5x10 per kilogram of body weight of the human subject receiving the product 7 one or more Tmem, about 7.0x10 per kilogram of body weight of the human subject receiving the product 7 one or more Tmem, about 7.5x10 per kilogram of body weight of the human subject receiving the product 7 one or more Tmem, about 8.0x10 per kilogram of body weight of the human subject receiving the product 7 one or more Tmem, about 8.5x10 per kilogram of body weight of the human subject receiving the product 7 one or more Tmem, about 9.0x10 per kilogram of body weight of the human subject receiving the product 7 one or more Tmem, about 9.5x10 per kilogram of body weight of the human subject receiving the product 7 one or more Tmem or about 1.0x10 per kilogram of body weight of the human subject receiving the product 8 one or more Tmem; and / or h) the population consisting of isolated CD45 + cells contains about 5.0x10 5 or more Tmem, about 6.0x10 5 or more Tmem, about 7.0x10 5 or more Tmem, about 8.0x10 5 or more Tmem, about 9.0x10 5 or more Tmem, about 1.0x10 6 or more Tmem, about 1.5x10 6 or more Tmem, about 2.0x10 6 or more Tmem, about 2.5x10 6 or more Tmem, about 3.0x10 6 or more Tmem, about 3.5x10 6 or more Tmem, about 4.0x10 6 or more Tmem, about 4.5x10 6 or more Tmem, about 5.0x10 6 or more Tmem, about 5.5x10 6 or more Tmem, about 6.0x10 6 or more Tmem, about 6.5x10 6 or more Tmem, about 7.0x10 6 or more Tmem, about 7.5x10 6 or more Tmem, about 8.0x10 6 or more Tmem, about 8.5x10 6 or more Tmem, about 9.0x10 6 or more Tmem, about 9.5x10 6 or more Tmem, about 1.0x10 7 or more Tmem, about 1.5x10 7 or more Tmem, about 2.0x10 7 or more Tmem, about 2.5x10 7 or more Tmem, about 3.0x10 7 or more Tmem, about 3.5x10 7 or more Tmem, about 4.0x10 7 or more Tmem, about 4.5x10 7 one or more Tmem, approximately 5.0x10 7 one or more Tmem, approximately 5.5x10 7 one or more Tmem, approximately 6.0x10 7 one or more Tmem, approximately 6.5x10 7 one or more Tmem, approximately 7.0x10 7 one or more Tmem, approximately 7.5x10 7 one or more Tmem, approximately 8.0x10 7 one or more Tmem, approximately 8.5x10 7 one or more Tmem, approximately 9.0x10 7 one or more Tmem, approximately 9.5x10 7 one or more Tmem, approximately 1.0x10 8 one or more Tmem, approximately 1.5x10 8 one or more Tmem, approximately 2.0x10 8 one or more Tmem, approximately 2.5x10 8 one or more Tmem, approximately 3.0x10 8 one or more Tmem, approximately 3.5x10 8 one or more Tmem, approximately 4.0x10 8 one or more Tmem, approximately 4.5x10 8 one or more Tmem, approximately 5.0x10 8 one or more Tmem, approximately 5.5x10 8 one or more Tmem, approximately 6.0x10 8 one or more Tmem, approximately 6.5x10 8 one or more Tmem, approximately 7.0x10 8 one or more Tmem, approximately 7.5x10 8 one or more Tmem, approximately 8.0x10 8 one or more Tmem, approximately 8.5x10 8 one or more Tmem, approximately 9.0x10 8 one or more Tmem, approximately 9.5x10 8 one or more Tmem, approximately 1.0x10 9 one or more Tmem, approximately 1.5x10 9 one or more Tmem, approximately 2.0x10 9 one or more Tmem, approximately 2.5x10 9 one or more Tmem, approximately 3.0x10 9 one or more Tmem, approximately 3.5x10 9 one or more Tmem, approximately 4.0x10 9 one or more Tmem, approximately 4.5x10 9 one or more Tmem, approximately 5.0x10 9 one or more Tmem, approximately 5.5x10 9 one or more Tmem, approximately 6.0x10 9 one or more Tmem, approximately 6.5x10 9 one or more Tmem, approximately 7.0x10 9 one or more Tmem, approximately 7.5x10 9 one or more Tmem, approximately 8.0x10 9 one or more Tmem, approximately 8.5x10 9 one or more Tmem, approximately 9.0x10 9 one or more Tmem, approximately 9.5x10 9 one or more Tmem, approximately 1.0x10 10 one or more Tmem or approximately 1.5x10 10 one or more Tmem; and / or i) The population consisting of isolated CD45 + cells contains from about 1.0x10 5 to about 2.0x10 7 fresh Tregs per kilogram of body weight of the human subject; and / or 5 from about 5.0x10 9 to about 3.0x10 j) the population consisting of isolated CD45 + cells contains about 1.0x10 5 or more fresh Tregs per kg of body weight of the human subject, about 2.0x10 5 or more fresh Tregs per kg of body weight of the human subject, about 3.0x10 5 or more fresh Tregs per kg of body weight of the human subject, about 4.0x10 5 or more fresh Tregs per kg of body weight of the human subject, about 5.0x10 5 or more fresh Tregs per kg of body weight of the human subject, about 6.0x10 5 or more fresh Tregs per kg of body weight of the human subject, about 7.0x10 5 or more fresh Tregs per kg of body weight of the human subject, about 8.0x10 5 or more fresh Tregs per kg of body weight of the human subject, about 9.0x10 5 or more fresh Tregs per kg of body weight of the human subject, about 1.0x10 6 or more fresh Tregs per kg of body weight of the human subject, about 1.5x10 6 or more fresh Tregs per kg of body weight of the human subject, about 2.0x10 6 or more fresh Tregs per kg of body weight of the human subject, about 2.5x10 6 or more fresh Tregs per kg of body weight of the human subject, about 3.0x10 6 or more fresh Tregs per kg of body weight of the human subject, about 3.5x10 6 or more fresh Tregs per kg of body weight of the human subject, about 4.0x10 6 or more fresh Tregs per kg of body weight of the human subject, about 4.5x10 6 or more fresh Tregs per kg of body weight of the human subject, about 5.0x10 6 or more fresh Tregs per kg of body weight of the human subject, about 5.5x10 6 or more fresh Tregs per kg of body weight of the human subject, about 6.0x10 6 or more fresh Tregs per kg of body weight of the human subject, about 6.5x10 6 one or more fresh Tregs, approximately 7.0x10 per kilogram of the body weight of the human subject 6 one or more fresh Tregs, approximately 7.5x10 per kilogram of the body weight of the human subject 6 one or more fresh Tregs, approximately 8.0x10 per kilogram of the body weight of the human subject 6 one or more fresh Tregs, approximately 8.5x10 per kilogram of the body weight of the human subject 6 one or more fresh Tregs, approximately 9.0x10 per kilogram of the body weight of the human subject 6 one or more fresh Tregs, approximately 9.5x10 per kilogram of the body weight of the human subject 6 one or more fresh Tregs, approximately 1.0x10 per kilogram of the body weight of the human subject 7 one or more fresh Tregs, approximately 1.5x10 per kilogram of the body weight of the human subject 7 one or more fresh Tregs or approximately 2.0x10 per kilogram of the body weight of the human subject 7 one or more fresh Tregs; and / or k) The population consisting of isolated CD45 + cells contains approximately 5.0x10 5 or more fresh Tregs, approximately 6.0x10 5 or more fresh Tregs, approximately 7.0x10 5 or more fresh Tregs, approximately 8.0x10 5 or more fresh Tregs, approximately 9.0x10 5 or more fresh Tregs, approximately 1.0x10 6 or more fresh Tregs, approximately 1.5x10 6 or more fresh Tregs, approximately 2.0x10 6 or more fresh Tregs, approximately 2.5x10 6 or more fresh Tregs, approximately 3.0x10 6 or more fresh Tregs, approximately 3.5x10 6 or more fresh Tregs, approximately 4.0x10 6 or more fresh Tregs, approximately 4.5x10 6 or more fresh Tregs, approximately 5.0x10 6 or more fresh Tregs, approximately 5.5x10 6 or more fresh Tregs, approximately 6.0x10 6 or more fresh Tregs, approximately 6.5x10 6 or more fresh Tregs, approximately 7.0x10 6 or more fresh Tregs, approximately 7.5x10 6 or more fresh Tregs, approximately 8.0x10 6 or more fresh Tregs, approximately 8.5x10 6 or more fresh Tregs, approximately 9.0x10 6 or more fresh Tregs, approximately 9.5x10 6 or more fresh Tregs, approximately 1.0x10 7 or more fresh Tregs, approximately 1.5x10 7 or more fresh Tregs, approximately 2.0x10 7 or more fresh Tregs, approximately 2.5x10 7 or more fresh Tregs, approximately 3.0x10 7 or more fresh Tregs, approximately 3.5x10 7 One or more fresh Tregs, approximately 4.0x10 7 One or more fresh Tregs, approximately 4.5x10 7 One or more fresh Tregs, approximately 5.0x10 7 One or more fresh Tregs, approximately 5.5x10 7 One or more fresh Tregs, approximately 6.0x10 7 One or more fresh Tregs, approximately 6.5x10 7 One or more fresh Tregs, approximately 7.0x10 7 One or more fresh Tregs, approximately 7.5x10 7 One or more fresh Tregs, approximately 8.0x10 7 One or more fresh Tregs, approximately 8.5x10 7 One or more fresh Tregs, approximately 9.0x10 7 One or more fresh Tregs, approximately 9.5x10 7 One or more fresh Tregs, approximately 1.0x10 8 One or more fresh Tregs, approximately 1.5x10 8 One or more fresh Tregs, approximately 2.0x10 8 One or more fresh Tregs, approximately 2.5x10 8 One or more fresh Tregs, approximately 3.0x10 8 One or more fresh Tregs, approximately 3.5x10 8 One or more fresh Tregs, approximately 4.0x10 8 One or more fresh Tregs, approximately 4.5x10 8 One or more fresh Tregs, approximately 5.0x10 8 One or more fresh Tregs, approximately 5.5x10 8 One or more fresh Tregs, approximately 6.0x10 8 One or more fresh Tregs, approximately 6.5x10 8 One or more fresh Tregs, approximately 7.0x10 8 One or more fresh Tregs, approximately 7.5x10 8 One or more fresh Tregs, approximately 8.0x10 8 One or more fresh Tregs, approximately 8.5x10 8 One or more fresh Tregs, approximately 9.0x10 8 One or more fresh Tregs, approximately 9.5x10 8 One or more fresh Tregs, approximately 1.0x10 9 One or more fresh Tregs, approximately 1.5x10 9 One or more fresh Tregs, approximately 2.0x10 9 One or more fresh Tregs, approximately 2.5x10 9 One or more fresh Tregs or approximately 3.0x10 9 One or more fresh Tregs; and / or l) The population consisting of isolated CD45 + cells contains less than about 5.0 x 10 5 Tcons per kilogram of body weight of the human subject receiving the product, less than about 4.5 x 10 5 Tcons per kilogram of body weight of the human subject receiving the product, less than about 4.0 x 10 5 Tcons per kilogram of body weight of the human subject receiving the product, less than about 3.5 x 10 5 Tcons per kilogram of body weight of the human subject receiving the product, less than about 3.0 x 10 5 Tcons per kilogram of body weight of the human subject receiving the product, less than about 2.5 x 10 5 Tcons per kilogram of body weight of the human subject receiving the product, less than about 2.0 x 10 5 Tcons per kilogram of body weight of the human subject receiving the product, less than about 1.5 x 10 5 Tcons per kilogram of body weight of the human subject receiving the product, less than about 1.0 x 10 5 Tcons per kilogram of body weight of the human subject receiving the product, less than about 9.5 x 10 4 Tcons per kilogram of body weight of the human subject receiving the product, less than about 9.0 x 10 4 Tcons per kilogram of body weight of the human subject receiving the product, less than about 8.5 x 10 4 Tcons per kilogram of body weight of the human subject receiving the product, less than about 8.0 x 10 4 Tcons per kilogram of body weight of the human subject receiving the product, less than about 7.5 x 10 4 Tcons per kilogram of body weight of the human subject receiving the product, less than about 7.0 x 10 4 Tcons per kilogram of body weight of the human subject receiving the product, less than about 6.5 x 10 4 Tcons per kilogram of body weight of the human subject receiving the product, less than about 6.0 x 10 4 Tcons per kilogram of body weight of the human subject receiving the product, less than about 5.5 x 10 4 Tcons per kilogram of body weight of the human subject receiving the product, less than about 5.0 x 10 4 Tcons per kilogram of body weight of the human subject receiving the product, less than about 4.5 x 10 4 a Tcon, less than about 4.0x10 per kg of body weight of the human subject receiving the product 4 a Tcon, less than about 3.5x10 per kg of body weight of the human subject receiving the product 4 a Tcon, less than about 3.0x10 per kg of body weight of the human subject receiving the product 4 a Tcon, less than about 2.5x10 per kg of body weight of the human subject receiving the product 4 a Tcon, less than about 2.0x10 per kg of body weight of the human subject receiving the product 4 a Tcon, less than about 1.5x10 per kg of body weight of the human subject receiving the product 4 a Tcon, less than about 1.0x10 per kg of body weight of the human subject receiving the product 4 a Tcon, less than about 9.5x10 per kg of body weight of the human subject receiving the product 3 a Tcon, less than about 9.0x10 per kg of body weight of the human subject receiving the product 3 a Tcon, less than about 8.5x10 per kg of body weight of the human subject receiving the product 3 a Tcon, less than about 8.0x10 per kg of body weight of the human subject receiving the product 3 a Tcon, less than about 7.5x10 per kg of body weight of the human subject receiving the product 3 a Tcon, less than about 7.0x10 per kg of body weight of the human subject receiving the product 3 a Tcon, less than about 6.5x10 per kg of body weight of the human subject receiving the product 3 a Tcon, less than about 6.0x10 per kg of body weight of the human subject receiving the product 3 a Tcon, less than about 5.5x10 per kg of body weight of the human subject receiving the product 3 a Tcon, less than about 5.0x10 per kg of body weight of the human subject receiving the product 3 a Tcon, less than about 4.5x10 per kg of body weight of the human subject receiving the product 3 a Tcon, less than about 4.0x10 per kg of body weight of the human subject receiving the product 3 a Tcon, less than about 3.5x10 per kg of body weight of the human subject receiving the product 3 Tcons, less than about 3.0x10 per kilogram of body weight of the human subject receiving the product 3 Tcons, less than about 2.5x10 per kilogram of body weight of the human subject receiving the product 3 Tcons, less than about 2.0x10 per kilogram of body weight of the human subject receiving the product 3 Tcons, less than about 1.5x10 per kilogram of body weight of the human subject receiving the product 3 Tcons or less than about 1.0x10 per kilogram of body weight of the human subject receiving the product 3 Tcons; and / or m) the population consisting of isolated CD45 + cells contains fewer than about 6.0x10 7 Tcon, fewer than about 5.5x10 7 Tcon, fewer than about 5.0x10 7 Tcon, fewer than about 4.5x10 7 Tcon, fewer than about 4.0x10 7 Tcon, fewer than about 3.5x10 7 Tcon, fewer than about 3.0x10 7 Tcon, fewer than about 2.5x10 7 Tcon, fewer than about 2.0x10 7 Tcon, fewer than about 1.5x10 7 Tcon, fewer than about 1.0x10 7 Tcon, fewer than about 9.5x10 6 Tcon, fewer than about 9.0x10 6 Tcon, fewer than about 8.5x10 6 Tcon, fewer than about 8.0x10 6 Tcon, fewer than about 7.5x10 6 Tcon, fewer than about 7.0x10 6 Tcon, fewer than about 6.5x10 6 Tcon, fewer than about 6.0x10 6 Tcon, fewer than about 5.5x10 6 Tcon, fewer than about 5.0x10 6 Tcon, fewer than about 4.5x10 6 Tcon, fewer than about 4.0x10 6 Tcon, fewer than about 3.5x10 6 Tcon, fewer than about 3.0x10 6 Tcon, fewer than about 2.5x10 6 Tcon, fewer than about 2.0x10 6 Tcon, fewer than about 1.5x10 6 Tcon or fewer than about 1.0x10 6 Tcon; and / or n) the population consisting of isolated CD45 + cells further comprises a population enriched in invariant natural killer T cells (iNKT) consisting of TCR Vα24Jα18 + CD127 + Optionally, the population consisting of isolated CD45 + cells contains from about 5.0×10 2 to about 2.0×10 6 iNKT per kg of body weight of the human subject receiving the product, or from about 2.0x10 3 to about 4.0x10 8 iNKT. Optionally, the population consisting of isolated CD45 + cells contains about 5.0x10 2 or more iNKT per kg of body weight of the human subject receiving the product, about 6.0x10 2 or more iNKT per kg of body weight of the human subject receiving the product, about 7.0x10 2 or more iNKT per kg of body weight of the human subject receiving the product, about 8.0x10 2 or more iNKT per kg of body weight of the human subject receiving the product, about 9.0x10 2 or more iNKT per kg of body weight of the human subject receiving the product, about 1.0x10 3 or more iNKT per kg of body weight of the human subject receiving the product, about 2.0x10 3 or more iNKT per kg of body weight of the human subject receiving the product, about 3.0x10 3 or more iNKT per kg of body weight of the human subject receiving the product, about 4.0x10 3 or more iNKT per kg of body weight of the human subject receiving the product, about 5.0x10 3 or more iNKT per kg of body weight of the human subject receiving the product, about 6.0x10 3 or more iNKT per kg of body weight of the human subject receiving the product, about 7.0x10 3 or more iNKT per kg of body weight of the human subject receiving the product, about 8.0x10 3 or more iNKT per kg of body weight of the human subject receiving the product, about 9.0x10 3 One or more iNKTs, approximately 1.0x10 per kilogram of body weight of the human subject receiving the product 4 One or more iNKTs, approximately 2.0x10 per kilogram of body weight of the human subject receiving the product 4 One or more iNKTs, approximately 3.0x10 per kilogram of body weight of the human subject receiving the product 4 One or more iNKTs, approximately 4.0x10 per kilogram of body weight of the human subject receiving the product 4 One or more iNKTs, approximately 5.0x10 per kilogram of body weight of the human subject receiving the product 4 One or more iNKTs, approximately 6.0x10 per kilogram of body weight of the human subject receiving the product 4 One or more iNKTs, approximately 7.0x10 per kilogram of body weight of the human subject receiving the product 4 One or more iNKTs, approximately 8.0x10 per kilogram of body weight of the human subject receiving the product 4 One or more iNKTs, approximately 9.0x10 per kilogram of body weight of the human subject receiving the product 4 One or more iNKTs, approximately 1.0x10 per kilogram of body weight of the human subject receiving the product 5 One or more iNKTs, approximately 2.0x10 per kilogram of body weight of the human subject receiving the product 5 One or more iNKTs, approximately 3.0x10 per kilogram of body weight of the human subject receiving the product 5 One or more iNKTs, approximately 4.0x10 per kilogram of body weight of the human subject receiving the product 5 One or more iNKTs, approximately 5.0x10 per kilogram of body weight of the human subject receiving the product 5 One or more iNKTs, approximately 6.0x10 per kilogram of body weight of the human subject receiving the product 5 One or more iNKTs, approximately 7.0x10 per kilogram of body weight of the human subject receiving the product 5 One or more iNKTs, approximately 8.0x10 per kilogram of body weight of the human subject receiving the product 5 One or more iNKTs, approximately 9.0x10 per kilogram of body weight of the human subject receiving the product 5 One or more iNKTs, approximately 1.0x10 per kilogram of body weight of the human subject receiving the product 6 One or more iNKTs, per kilogram of body weight of the human subject receiving the product, approximately 1.5x10 6 One or more iNKTs or per kilogram of body weight of the human subject receiving the product, approximately 2.0x10 6 One or more iNKTs, optionally wherein the population consisting of isolated CD45 + cells contains approximately 2.0x10 3 One or more iNKTs, approximately 3.0x10 3 One or more iNKTs, approximately 4.0x10 3 One or more iNKTs, approximately 5.0x10 3 One or more iNKTs, approximately 6.0x10 3 One or more iNKTs, approximately 7.0x10 3 One or more iNKTs, approximately 8.0x10 3 One or more iNKTs, approximately 9.0x10 3 One or more iNKTs, approximately 1.0x10 4 One or more iNKTs, approximately 2.0x10 4 One or more iNKTs, approximately 3.0x10 4 One or more iNKTs, approximately 4.0x10 4 One or more iNKTs, approximately 5.0x10 4 One or more iNKTs, approximately 6.0x10 4 One or more iNKTs, approximately 7.0x10 4 One or more iNKTs, approximately 8.0x10 4 One or more iNKTs, approximately 9.0x10 4 One or more iNKTs, approximately 1.0x10 5 One or more iNKTs, approximately 2.0x10 5 One or more iNKTs, approximately 3.0x10 5 One or more iNKTs, approximately 4.0x10 5 One or more iNKTs, approximately 5.0x10 5 One or more iNKTs, approximately 6.0x10 5 One or more iNKTs, approximately 7.0x10 5 One or more iNKTs, approximately 8.0x10 5 One or more iNKTs, approximately 9.0x10 5 One or more iNKTs, approximately 1.0x10 6 One or more iNKTs, approximately 1.5x10 6 One or more iNKTs, approximately 2.0x10 6 One or more iNKTs, approximately 2.5x10 6 One or more iNKTs, approximately 3.0x10 6 One or more iNKTs, approximately 3.5x10 6 One or more iNKTs, approximately 4.0x10 6 One or more iNKTs, approximately 4.5x10 6 One or more iNKTs, approximately 5.0x10 6 One or more iNKTs, approximately 5.5x10 6 One or more iNKTs, approximately 6.0x10 6 One or more iNKTs, approximately 6.5x10 6 One or more iNKTs, approximately 7.0x10 6 One or more iNKTs, approximately 7.5x10 6 One or more iNKTs, approximately 8.0x10 6 One or more iNKTs, approximately 8.5x10 6 One or more iNKTs, approximately 9.0x10 6 One or more iNKTs, approximately 9.5x10 6 One or more iNKTs, approximately 1.0x10 7 One or more iNKTs, approximately 1.5x10 7 One or more iNKTs, approximately 2.0x10 7 One or more iNKTs, approximately 2.5x10 7 One or more iNKTs, approximately 3.0x10 7 One or more iNKTs, approximately 3.5x10 7 One or more iNKTs, approximately 4.0x10 7 One or more iNKTs, approximately 4.5x10 7 One or more iNKTs, approximately 5.0x10 7 One or more iNKTs, approximately 5.5x10 7 One or more iNKTs, approximately 6.0x10 7 One or more iNKTs, approximately 6.5x10 7 One or more iNKTs, approximately 7.0x10 7 One or more iNKTs, approximately 7.5x10 7 One or more iNKTs, approximately 8.0x10 7 One or more iNKTs, approximately 8.5x10 7 one or more iNKTs, approximately 9.0x10 7 one or more iNKTs, approximately 9.5x10 7 one or more iNKTs, approximately 1.0x10 8 one or more iNKTs, approximately 1.5x10 8 one or more iNKTs, approximately 2.0x10 8 one or more iNKTs, approximately 2.5x10 8 one or more iNKTs, approximately 3.0x10 8 one or more iNKTs, approximately 3.5x10 8 one or more iNKTs or approximately 4.0x10 8 one or more iNKTs, optionally wherein the iNKT is CD1d-tet + 、6B11 + or CD1d-tet + 6B11 + ; and / or o) wherein the population consisting of isolated CD45 + cells is from an allogeneic donor having at least one HLA mismatch relative to the 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 includes a population composed of T central memory cells (T CM ), a population composed of T effector memory cells (T EM ), a population composed of T stem cell central memory cells (T SCM ), or any combination thereof, optionally where the T CM is CD4 + CD45RO + or CD8 + CD45RO + , and / or the T CM is CD45RA - , CD62L + , CCR7 + , or any combination thereof, optionally where the T EM is CD4 + , CD45RO + , CD45RA - , CD62L - , CCR7 - , or any combination thereof, optionally where the T 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) The Tregs comprise a population consisting of naive Treg cells, a population consisting of memory Treg cells, or a population consisting of naive Treg cells and memory Treg cells, optionally wherein the naive Treg cells are CD4 + CD25 + CD127 dim FoxP3 + CD45RA + CD45RO - , optionally wherein the Tregs comprise from about 2.0 x 10 5 to about 5.0 x 10 8 naive Treg cells or from about 8.0 x 10 5 to about 1.0 x 10 11 naive Treg cells per kilogram of body weight of the human subject receiving the product, optionally wherein the memory Treg cells are CD4 + CD25 + CD127 dim FoxP3 + CD45RA - CD45RO + , optionally wherein said Treg comprises from about 5.0x10 4 per kg body weight of the human subject receiving said product to about 5.0x10 8 memory Treg cells or from about 2.0x10 5 to about 1.0x10 11 memory Treg cells; and / or u) The Tcon is TCRα + , TCRβ + or TCRα + TCRβ + , and / or the Tcon is CD25 - , CD127 + or CD25 - CD127 + , and / or the Tcon is TCRα + TCRβ + CD45RA + CD45RO - CD25 - CD95 - IL-2Rβ - CD127 + ; and / or v) the population of isolated CD45 + cells contains less than about 5 EU to less than about 0.5 EU of endotoxin per mL of the preparation; and / or w) the HSPC, the Tmem, the Treg, or any combination thereof is obtained from an allogeneic donor HLA-matched to the human subject receiving the product, or the population consisting of isolated CD45 + cells is from an allogeneic donor HLA-matched to the human subject receiving the product; and / or x) The HSPC, the Tmem, the Treg, or any combination thereof is obtained from an allogeneic donor having at least one HLA mismatch relative to the human subject receiving the product, or the population consisting of isolated CD45 + cells is from an allogeneic donor having at least one HLA mismatch relative to the human subject receiving the product, optionally wherein 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, optionally wherein the cells having at least one HLA mismatch are from a donor that is 6 / 8 HLA mismatched relative to the human subject receiving the product, or the cells having at least one HLA mismatch are from a donor that is 7 / 8 HLA mismatched relative to the human subject receiving the product, optionally wherein the cells having at least one HLA mismatch are from a donor that is 7 / 8 HLA mismatched relative to the human subject receiving the product, optionally wherein the donor that is 7 / 8 HLA mismatched relative to the human subject receiving the product has a mismatch in HLA-A, optionally wherein the donor that is 7 / 8 HLA mismatched relative to the human subject receiving the product has a mismatch in HLA-B, optionally wherein the donor that is 7 / 8 HLA mismatched relative to the human subject receiving the product has a mismatch in HLA-C, optionally wherein the donor that is 7 / 8 HLA mismatched relative to the human subject receiving the product has a mismatch in HLA-DRB1, optionally wherein the donor having the 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 while the human subject receiving the product is heterozygous for the HLA allele, optionally wherein the donor having the 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 while the human subject receiving the product is homozygous for the HLA allele, optionally wherein the donor having the at least one HLA mismatch relative 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; and / or y) the HSPC, the Tmem, the Treg, or any combination thereof is obtained from a donor who is haploidentical relative to the human subject receiving the product, or the population consisting of isolated CD45 + cells is from a donor who is haploidentical 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) The overall survival rate at 12 months or more after administration of the cell therapy product ranges from about 75% to about 100%; and / or bb) The overall survival rate of the human subject is increased after administration of the cell therapy product relative to a corresponding human subject who has received a standard myeloablative allogeneic hematopoietic stem cell transplantation (alloHSCT); and / or cc) The graft-versus-host disease-free and relapse-free survival (GFRS) rate at 12 months or more after administration of the cell therapy product ranges from about 65% to about 100%; and / or dd) The graft-versus-host disease-free and relapse-free survival (GFRS) rate of the human subject is increased after administration of the cell therapy product relative to a corresponding human subject who has received a standard myeloablative allogeneic hematopoietic stem cell transplantation (alloHSCT); and / or ee) The relapse-free survival rate at 12 months or more after administration of the cell therapy product ranges from about 70% to about 100%; and / or ff) The relapse-free survival rate of the human subject is increased after administration of the cell therapy product relative to a corresponding human subject who has received a standard myeloablative allogeneic hematopoietic stem cell transplantation (alloHSCT); and / or gg) wherein the incidence of acute graft-versus-host disease at 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 graft-versus-host disease at 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) at 100 days or more after administration of the cell therapy product ranges from approximately 1% to approximately 10%; and / or jj) The incidence of grade 2 or higher infections at 100 days or more after administration of the cell therapy product ranges from approximately 23% to approximately 31%.

9. The method according to claim 7 or claim 8, wherein the method further comprises administering a conditioning regimen prior to administering the cell therapy product, optionally wherein the conditioning regimen is administered about two to about ten days before administering the multi-component cell therapy, optionally wherein the conditioning regimen is a total body irradiation (TBI)-based regimen or a total lymphoid irradiation (TLI)-based regimen, optionally wherein the TBI-based regimen comprises fractionated total body irradiation, optionally wherein the fractionated total body irradiation comprises 2 or more, 3 or more, 4 or more, 5 or more, 6 or more, 7 or more, 8 or more, 9 or more, 10 or more, 11 or more, 12 or more, 13 or more, 14 or more, or 15 or more doses, optionally wherein the fractionated total body irradiation comprises a total dose ranging from about 500 cGy to about 1600 cGy, optionally wherein the TBI-based regimen further comprises one or more conditioning reagents, optionally wherein the one or more conditioning reagents are selected from the group consisting of cyclophosphamide, etoposide, fludarabine, thiotepa, antithymocyte globulin (ATG), and any combination thereof, optionally wherein the conditioning regimen is a myeloablative conditioning regimen, optionally wherein the myeloablative conditioning regimen comprises 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, optionally wherein the myeloablative conditioning regimen comprises three or more conditioning reagents, wherein at least one conditioning reagent comprises thiotepa, optionally wherein the myeloablative conditioning regimen comprises one or more doses of busulfan, fludarabine, and thiotepa, optionally wherein the one or more doses of busulfan, fludarabine, and thiotepa comprise about 5 mg to about 12 mg of thiotepa per kilogram of the body weight of the human subject, about 7 mg to about 11 mg of busulfan per kilogram of the body weight of the human subject, and about 100 mg to about 200 mg of fludarabine per square meter of body surface area, respectively.

10. The method according to any one of claims 7 to 9, wherein the method further comprises collecting one or more mobilized peripheral blood donations from the donor, optionally wherein the peripheral blood donation is mobilized by granulocyte colony-stimulating factor (G-CSF), granulocyte macrophage colony-stimulating factor (GM-CSF), plerixafor, or any combination thereof, optionally wherein at least one of the mobilized peripheral blood donations is treated and sorted using one or more immunoisolation particles (ISPs) to enrich for HSPCs, Tmem, and Tregs, optionally wherein the one or more ISPs comprise an affinity reagent, optionally wherein the affinity reagent is an immunomagnetic separation particle, optionally wherein the immunomagnetic separation particle is an antibody conjugated to an iron-containing particle, optionally wherein the affinity reagent comprises a plurality of CD34 reagents that bind to CD34 on HSPCs, optionally wherein the average number of ISPs per HSPC in the population consisting of the isolated CD45 + cells is equal to or less than about 20,000, optionally wherein the average number of ISPs per HSPC in the population consisting of the isolated CD45 + cells is from about 1000 to about 20,000, optionally wherein the affinity reagent comprises a plurality of CD45RA reagents that bind to one or more CD45RA receptors on Tmem, optionally wherein the affinity reagent comprises a plurality of CD25 reagents that bind to one or more CD25 receptors on Tregs, optionally wherein the average number of ISPs per Treg in the population consisting of the isolated CD45 + cells is equal to or less than about 4000, optionally wherein the average number of ISPs per Treg in the population consisting of the isolated CD45 + cells is from about 1500 to about 2500.

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

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

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

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

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

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