ORDERED PROCESSING OF BLOOD PRODUCTS TO PRODUCE THERAPEUTICALLY ACTIVE CELLS

1 . A method for processing a blood related sample comprising: (a) providing a blood related sample comprising one or more target cells, platelet cells, red blood cells; and (b) reducing a number of the platelet cells in the blood related sample while maintaining a ratio of the red blood cells to the one or more target cells greater than about 50:1 to produce a reduced platelet blood related sample comprising the one or more target cells.

2 . The method of claim 1 , wherein the blood related sample comprises a hematocrit of greater than about 2%.

3 . The method of claim 1 , wherein the blood related sample comprises a hematocrit of greater than about 4%.

4 . The method of claim 1 , wherein the blood related sample comprises a hematocrit of less than about 30%.

5 . The method of claim 1 , wherein the blood related sample is a leukapheresis product.

6 . The method of any one of claims 1 to 5 , wherein the reduced platelet blood related sample comprises a ratio of platelets to target cells of less than about 500:1.

7 . The method of claim 6 , wherein the reduced platelet blood related sample comprises a ratio of platelets to target cells of less than about 100:1.

8 . The method of claim 6 , wherein the reduced platelet blood related sample comprises a ratio of platelets to target cells of less than about 10:1.

9 . The method of claim 6 , wherein the reduced platelet blood related sample comprises a ratio of platelets to target cells of less than about 5:1.

10 . The method of any one of claims 1 to 9 , wherein the red blood cells are maintained at a ratio of red blood cells to target cells of greater than about 100:1.

11 . The method of claim 10 , wherein the red blood cells are maintained at a ratio of red blood cells to target cells of greater than about 250:1.

12 . The method of claim 10 , wherein the red blood cells are maintained at a ratio of red blood cells to target cells of greater than about 500:1.

13 . The method of claim 10 , wherein the red blood cells are maintained at a ratio of red blood cells to target cells of no greater than about 1,000:1.

14 . The method of any one of claims 1 to 13 , further comprising removing one or more non-target cells from the blood related sample and/or the reduced platelet blood related sample.

15 . The method of claim 14 , wherein the one or more non-target cells comprise immune suppressive cells.

16 . The method of claim 15 , wherein the immune suppressive cells are regulatory T cells.

17 . The method of claim 15 , wherein the immune suppressive cells are regulatory B cells.

18 . The method of claim 15 , wherein the immune suppressive cells comprise myeloid derived suppressor cells.

19 . The method of any one of any one of claims 14 to 18 , wherein the non-target cells are removed by an affinity-based method.

20 . The method of claim 19 , wherein the affinity-based method targets a molecule on the cell surface of the non-target cells.

21 . The method of claim 19 or 20 , wherein the affinity-based method comprises the use of an antibody.

22 . The method of claim 21 , wherein the antibody is conjugated to biotin, streptavidin, a fluorescent moiety, or a magnetic material.

23 . The method of any one of claims 1 to 22 , comprising adding an anticoagulant to the blood related sample.

24 . The method of any one of claims 1 to 23 , wherein the blood related sample is a human blood related sample.

25 . The method of any one of claims 1 to 24 , wherein the blood related sample is collected from an individual afflicted with a cancer or a tumor or an HLA matched individual to the individual afflicted with a cancer or a tumor.

26 . The method of claim 25 , wherein the blood related sample is collected from an individual afflicted with a cancer or a tumor.

27 . The method of any one of claims 1 to 26 , wherein reducing the number of the platelet cells from the blood related sample comprises use of a method which uses an affinity reagent, a deterministic lateral displacement method, a method which uses a density media, an acoustophoretic method, or a dielectrophoretic method.

28 . The method of claim 27 , wherein reducing the number of the platelet cells from the blood related sample uses a method comprising deterministic lateral flow.

29 . The method of any one of claims 1 to 28 , further comprising isolating the one or more target cells from the reduced platelet blood related sample to produce one or more isolated target cells.

30 . The method of any one of claims 1 to 29 , wherein the one or more target cells comprise peripheral blood mononuclear cells.

31 . The method of any one of claims 1 to 29 , wherein the one or more target cells comprise a stem cell, a lymphoid cell, or a myeloid cell.

32 . The method of claim 30 , wherein the stem cell is a hematopoietic stem cell.

33 . The method of claim 30 , wherein the lymphoid cell is a T cell.

34 . The method of claim 33 , wherein the T cell displays a naïve phenotype.

35 . The method of claim 33 , wherein the T cell displays a central memory phenotype.

36 . The method of claim 30 , wherein the lymphoid cell is a natural killer cell or a natural killer T cell.

37 . The method of claim 30 , wherein the myeloid cell is a dendritic cell.

38 . The method of claim 30 , wherein the myeloid cell is a macrophage cell.

39 . The method of any one of claims 29 to 38 , wherein the one or more target cells are isolated by a method which uses an affinity reagent, a deterministic lateral displacement method, a method which uses a density media, an acoustophoretic method, or a dielectrophoretic method.

40 . The method of any one of claims 29 to 38 , wherein the one or more target cells are isolated by a method which uses an affinity reagent.

41 . The method of any one of claims 29 to 38 , wherein the one or more target cells are isolated using deterministic lateral displacement.

42 . The method of any one of claims, 1 to 41 , further comprising culturing the one or more target cells of the reduced platelet blood related sample or the one or more isolated target cells.

43 . The method of any one of claims, 1 to 41 , further comprising genetically engineering the one or more target cells of the reduced platelet blood related sample or the one or more isolated target cells.

44 . The method of claim 43 , wherein the genetic engineering comprises rendering the one or more target cells transgenic for a chimeric antigen receptor.

45 . The method of claim 43 , wherein the genetic engineering comprises rendering the one or more target cells transgenic for a recombinant T cell receptor.

46 . The method of any one of claims 43 to 45 , further comprising activating the one or more target cells prior to or after the genetic engineering.

47 . A cell population comprising one or more target cells, platelet cells and red blood cells, the target cells at a ratio of platelets to target cells less than about 500:1 and at a ratio of red blood cells to target cells of greater than about 50:1.

48 . The cell population of claim 47 , wherein the target cells comprise human cells.

49 . The cell population of claim 47 , wherein the target cells, platelet cells, and red blood cells comprise human cells.

50 . The cell population of any one of claims 47 to 50 , wherein the ratio of platelets to target cells is less than about 100:1.

51 . The cell population of any one of claims 47 to 50 , wherein the ratio of platelets to target cells is less than about 10:1.

52 . The cell population of any one of claims 47 to 50 , wherein the ratio of platelets to target cells is less than about 5:1.

53 . The cell population of any one of claims 47 to 52 , wherein the ratio of red blood cells to target cells is greater than about 100:1.

54 . The cell population of any one of claims 47 to 52 , wherein the ratio of red blood cells to target cells is greater than about 250:1.

55 . The cell population of any one of claims 47 to 52 , wherein the ratio of red blood cells to target cells is greater than about 500:1.

56 . The cell population of any one of claims 47 to 52 , wherein the ratio of red blood cells to target cells is greater than about 1,000:1.

57 . The cell population of any one of claims 47 to 56 , wherein the one or more target cells comprise peripheral blood mononuclear cells.

58 . The cell population of any one of claims 47 to 56 , wherein the one or more target cells comprise a stem cell, a lymphoid cell, or a myeloid cell.

59 . The cell population of claim 58 , wherein the stem cell is a hematopoietic stem cell.

60 . The cell population of claim 58 , wherein the lymphoid cell is a T cell.

61 . The cell population of claim 60 , wherein the T cell displays a naïve phenotype.

62 . The cell population of claim 60 , wherein the T cell displays a central memory phenotype.

63 . The cell population of claim 58 , wherein the lymphoid cell is a natural killer cell or a natural killer T cell.

64 . The cell population of claim 58 , wherein the myeloid cell is a dendritic cell.

65 . The cell population of claim 58 , wherein the myeloid cell is a macrophage cell.

66 . The cell population of any one of claims 47 to 65 , wherein the one or more target cells comprise an exogenous nucleic acid encoding a chimeric antigen receptor or a recombinant T cell receptor.

67 . The cell population of claim 47 , wherein the one or more target cells comprises an activated T cell.

68 . The cell population of any one of claims 47 to 67 , wherein the cell population is substantially free of one or more immune suppressive cells.

69 . The cell population of claim 68 , wherein the immune suppressive cells are regulatory T cells.

70 . The cell population of claim 68 , wherein the immune suppressive cells are regulatory B cells.

71 . The cell population of claim 68 , wherein the immune suppressive cells comprise myeloid derived suppressor cells.

72 . The cell population of any one of claims 47 to 71 , wherein the one or more target cells possess the capacity to divide at least 3 time before exhaustion.