Cytotherapeutics, cytotherapeutic units and methods for treatments using them

Abstract

The present invention provides cytotherapeutic units comprising predetermined numbers of selected types of potent cells. Assurance of the nature and identities of such cells is achieved through assay and certification of said numbers and identities. Therapeutic modalities are provided. Libraries of cell preparations with assayed and preferably certified populations are preferred and the preparation of cell preparations tailored to specific patients or disease states are provided.

Claims

1. A cytotherapeutic unit comprising a plurality of potent cells; the content of said unit being known with respect to the identities and numbers of at least some of said plurality; the unit being assayed to ensure the accuracy of said identities and numbers.

2. The cytotherapeutic unit of claim 1 wherein the accuracy of the assay is certified by the provider of the unit.

3. The cytotherapeutic unit of claim 1 wherein the potent cells for which the identities and numbers are known are pluripotent cells.

4. The cytotherapeutic unit of claim 1 wherein said identities reflect the presence or absence of at least one antigenic determinant on identified cells.

5. The cytotherapeutic unit of claim 1 wherein said potent cells are obtained from fetal cord blood or other fetal tissue

6. (canceled)

7. The cytotherapeutic unit of claim 1 wherein said potent cells are obtained from placenta.

8. (canceled)

9. (canceled)

10. The cytotherapeutic unit of claim 1 wherein potent cells for which the identities and numbers are known comprise at least some of the cells exhibiting CD34, CD8, CD10, OCT4.

11. The cytotherapeutic unit of claim 1 wherein potent cells are derived from a plurality of sources.

12. The cytotherapeutic unit of claim 1 wherein potent cells are derived from at least two individuals.

13. (canceled)

14. The cytotherapeutic unit of claim 1 wherein potent cells are genetically modified.

15. (canceled)

16. The cytotherapeutic unit of claim 1 wherein the plurality of potent cells is selected to render the cytotherapeutic unit suitable for therapy for an indicated disease state or condition.

17. (canceled)

18. A cytotherapeutic unit comprising minimum numbers of preselected types of potent cells.

19-25. (canceled)

26. A kit for treatment of a person suspected of having a disease state or condition comprising the cytotherapeutic unit of claim 1, additionally comprising a certification of the accuracy of the assay.

27. (canceled)

28. A kit for treatment of a person suspected of having a disease state or condition comprising the cytotherapeutic unit of claim 18, additionally comprising a certification of the potent cell composition of the unit.

29. (canceled)

30. (canceled)

31. The cytotherapeutic unit of claim 18, comprising cells derived from umbilical cord blood, placenta, or a mixture thereof, wherein at least one type of cell has been removed from the unit.

32. (canceled)

33. (canceled)

34. The cytotherapeutic unit of claim 18, comprising cells derived from umbilical cord blood, placenta, or a mixture thereof, said cells comprising a plurality of different types, at least some of the different types having been separated into components and recombined into said unit.

35. The cytotherapeutic unit of claim 34, wherein said separated cell types have been frozen separately.

36. (canceled)

37. (canceled)

38. (canceled)

39. A method of treating a disease in a mammal comprising administering to said mammal a therapeutically effective amount of a composition comprising the cytotherapeutic unit of claim 1.

40-49. (canceled)

50. A library of cytotherapeutic units, each unit member of said library comprising a plurality of potent cells; the content of each said units being known with respect to the identities and numbers at least some of the plurality of potent cells comprising said unit; each of said units being assayed to ensure the accuracy of said identities and numbers.

51. A method of treatment of a patient in need of cytotherapeutic treatment comprising selecting from the library of cytotherapeutic units of claim 50 at least two unit members of said library; combing aliquots from said unit members to form a treatment unit and administering said treatment unit to the patient.

52. (canceled)

53. (canceled)

Description

EXAMPLE 1

[0061] An adult having acute myelogenous leukemia (AML) is in need of hematopoetic reconstitution by way of a cell transplant. The patient undergoes traditional chemotherapy followed by conventional preparation for transplant as determined by the patient's healthcare provider but includes destroying the diseased bone marrow. The patient's weight is determined. Appropriate HLA typing has been done by conventional methods. Based on these parameters, which include the disease to be treated, the patient's body weight and HLA matching, the transplanter requests and is provided with a cytotherapeutic unit comprising a plurality of potent nucleated cells; the content of said unit being known with respect to the identities and numbers at least some of said plurality; the unit being assayed to ensure the accuracy of said identities and numbers, which is certified. In particular, the unit is certified to contain about 1.4×10.sup.7 nucleated cells per kilogram of the patient's body weight. Additional certified information includes HLA information. Because the patient suffers from AML, the cytotherapeutic unit contains no less than one (1) percent of CD34+ of the total nucleated cells and no less than 2.5 percent CD8+ cells to minimize graft versus tumor effect. In this case the transplanter requests twice the total number of cells needed for transplant (1.4×10.sup.7 nucleated cells multiplied by the patient's weight in kilograms ×2). The transplanter requests the 1× amount just prior to the transplant in order to have the number of cells suitable for this transplant. The second half of the cells is to be shipped in the event that a second transplant becomes necessary. Accordingly, the second cytotherapeutic unit is the same as that to be used in the initial transplant. Alternatively, the transplanter may request, based on alterations in the patient's weight, severity of disease or even changes in recommended treatment, that the second cytotherapeutic unit be altered in the appropriate manner (increased number of CD34 positive cells, etc.) and certified. The transplant is performed in the same manner conventionally used by the transplanter.

EXAMPLE 2

[0062] A child having sickle cell anemia is in need of a cell transplant. It is determined that 1.7×10.sup.7 nucleated cells per kilogram of body weight of the child is needed. Appropriate HLA typing is done by conventional methods. It is determined that the cytotherapeutic unit must have no less than 1% CD34+ cells of the total nucleated cells. Said CD34+ cells are further described in a ratio of 2:1 as CD34+/CD33+: CD34+/CD33.sup.−. A cytotherapeutic unit having these parameters is provided. This unit comprises cells derived from cord blood as well as pluripotential placental cells such as those described in WO 02/064755, which are derived in the manner described in WO02/064755. The ratio of CD34+/ CD33+ cells is 2:1 to CD34+/ CD33−, a fact which is ascertained by assay and certified as being accurate. The certified cells are determined using FACS; based on the fluorescent properties of the particles, cell surface marker-specific antibodies or ligands are labeled with distinct fluorescent labels. Cells are processed through the cell sorter, allowing separation of cells based on their ability to bind to the antibodies used. Cell surface marker-specific antibodies may be purchased from any company selling such reagents, including Becton Dickinson, for example. The transplant is performed in the same manner conventionally used by the transplanter.

EXAMPLE 3

[0063] A child suffers from adrenal leukodysplasia. It is determined that a cellular transplant is appropriate. It is determined that 2×10.sup.7 nucleated cells (derived from cord blood by a conventional technique) per kilogram of body weight of the child is needed. Appropriate HLA typing is done by conventional methods. A cytotherapeutic unit having these parameters is provided. In particular, the unit is certified to contain no less than 0.25% of CD34+/CD38− cells and with no less than 0.5% depletion of CD8+ cells of the total nucleated cells. The transplant is performed in the same manner conventionally used by the transplanter.