Method for improving autologous transplantation

• US 5,199,942 A
• Filed: 09/26/1991
• Issued: 04/06/1993
• Est. Priority Date: 06/07/1991
• Status: Expired due to Term

• Current Assignee: Immunex Corporation (Amgen Inc.)
• Original Assignee: Immunex Corporation (Amgen Inc.)
• Inventors: Gillis, Steven
• Primary Examiner(s): Rosenbaum, C. Fred
• Assistant Examiner(s): Polutta, Mark O.
• Application Number:
  US07/765,844
• Time in Patent Office: 558 Days
• Field of Search: 604/4-6, 604/48, 604/49, 128/898, 424/85.1, 424/85.2, 424/520, 424/529, 424/930, 424/93 V, 424/93 AA, 435/240.2, 435/240.21
• US Class Current: 604/4.01
• CPC Class Codes: A61K 2035/122 for inducing tolerance or supression of immune responses
• CPC Class Codes: A61K 2035/124 the cells being hematopoietic, bone marrow derived or blood cells
• CPC Class Codes: A61K 35/28 Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: C12N 2501/125 Stem cell factor [SCF], c-kit ligand [KL]
• CPC Class Codes: C12N 2501/22 Colony stimulating factors (G-CSF, GM-CSF)
• CPC Class Codes: C12N 2501/23 Interleukins [IL]
• CPC Class Codes: C12N 5/0647 Haematopoietic stem cells; Uncommitted or multipotent progenitors

Abstract

There is disclosed a method for autologous hematopoietic cell transplantation of patients receiving cytoreductive therapy, comprising: (1) obtaining hematopoietic progenitor cells from bone marrow or peripheral blood from a patient prior to cytoreductive therapy; (2) expanding the hematopoietic progenitor cells ex vivo with an ex vivo growth factor selected from the group consisting of interleukin-3 (IL-3), steel factor (SF), granulocyte macrophage-colony stimulating factor (GM-CSF), interleukin-1 (IL-1), GM-CSF/IL-3 fusion proteins and combinations thereof, to provide a cellular preparation comprising an expanded population of progenitor cells; and (3) administering the cellular preparation to the patient concurrently with or follwoing cytoreductive therapy. The inventive method optionally comprising a preliminary treatment with a recruitment growth factor to recruit hematopoietic progenitor cells into peripheral blood and a subsequent treatment with an engraftment growth factor to facilitate engraftment and proliferation of hematopoietic progenitor cells administered in the cellular preparation. The invention further provides a hematopoietic progenitor cell expansion media composition comprising cell media, an ex vivo growth factor, and autologous serum.

Claims

1. A method for autologous hematopoietic cell transplantation in a patient receiving cytoreductive therapy, comprising:

a. removing hematopoietic progenitor cells from the patient prior to cytoreductive therapy;

b. expanding the hematopoietic progenitor cells ex vivo with

(1) a growth factor comprising granulocyte macrophage-colony stimulating factor (GM-CSF) combined with interleukin-3 (IL-3), or a GM-CSF/IL-3 fusion protein, and

(2) one or more growth factors selected from the group consisting of steel factor (SF), interleukin-1 (IL-1) and granulocyte-colony stimulating factor (G-CSF) and combinations thereof,

to provide a cellular preparation comprising an expanded population of hematopoietic progenitor cells; and

c. administering the cellular preparation to the patient following cytoreductive therapy.

2. The method of claim 1 wherein the growth factor comprises a GM-CSF/IL-3 fusion protein.

3. The method of claim 1 wherein the growth factor comprises SF and a Leu²³ Asp²⁷ Glu³⁴ hGM-CSF/Gly₄ Ser Gly₅ Ser/Pro⁸ Asp¹⁵ Asp⁷⁰ hIL-3 fusion protein.

4. The method of claim 1 wherein the ex vivo growth factor comprises IL-1α

and Leu²³ Asp²⁷ Glu³⁴ hGM-CSF/Gly₄ Ser Gly₅ Ser/Pro⁸ Asp¹⁵ Asp⁷⁰ hIL-3 fusion protein, or a combination of SF, IL-1α and

Leu²³ Asp²⁷ Glu³⁴ hGM-CSF/Gly₄ Ser Gly₅ Ser/Pro⁸ Asp¹⁵ Asp⁷⁰ hIL-3 fusion protein.

5. The method of claim 1 wherein the hematopoietic progenitor cell are obtained from peripheral blood.

6. The method of claim 1 wherein the hematopoietic progenitor cells are obtained from bone marrow.

7. The method of claim 1 further comprising the step of subsequently treating the patient in vivo with an engraftment growth factor for 3 to 21 days following administrating the cellular preparation to the patient, wherein the engraftment growth factor is selected from the group consisting of GM-CSF, IL-3, SF, GM-CSF/IL-3 fusion proteins and combinations thereof.

8. The method of claim 7 wherein the engraftment growth factor comprises SF and a GM-CSF/IL-3 fusion protein.

9. The method of claim 1 further comprising the step of pre-treating the patient with a recruitment growth factor in vivo for 1-7 days prior to removing hematopoietic progenitor cells, wherein the recruitment growth factor is selected from the group consisting of GM-CSF, IL-3, SF, GM-CSF/IL-3 fusion proteins and combinations thereof.

10. The method of claim 9, wherein the ex vivo growth factor and the in vivo recruitment growth factor comprise a GM-CSF/IL-3 fusion protein.

11. The method of claim 9, wherein the ex vivo growth factor comprises SF and Leu²³ Asp²⁷ Glu³⁴ hGM-CSF/Gly₄ Ser Gly₅ Ser/Pro⁸ Asp¹⁵ Asp⁷⁰ hIL-3 fusion protein.

12. The method of claim 9 wherein the ex vivo growth factor comprises IL-1α

and Leu²³ Asp²⁷ Glu³⁴ hGM-CSF/Gly₄ Ser Gly₅ Ser/Pro⁸ Asp¹⁵ Asp⁷⁰ hIL-3 fusion protein, or a combination of SF, IL-1α and

Leu²³ Asp²⁷ Glu³⁴ hGM-CSF/Gly₄ Ser Gly₅ Ser/Pro⁸ Asp¹⁵ Asp⁷⁰ hIL-3 fusion protein.

13. The method of claim 9 wherein the in vivo recruitment growth factor comprises SF and GM-CSF.

14. The method of claim 9 wherein the hematopoietic progenitor cells are obtained from peripheral blood.

15. The method of claim 9 wherein the hematopoietic progenitor cells are obtained from bone marrow.

16. The method of claim 9 further comprising the step of subsequently treating the patient in vivo with an engraftment growth factor for 3 to 21 days following administrating the cellular preparation to the patient, wherein the engraftment growth factor is selected from the group consisting of GM-CSF, IL-3, SF, GM-CSF/IL-3 fusion proteins and combinations thereof.

17. The method of claim 16 wherein the engraftment growth factor comprises SF and a GM-CSF/IL-3 fusion protein.