EP1660105A1 - Method of replenishing cells damaged by treatment for cancer - Google Patents

Method of replenishing cells damaged by treatment for cancer

Info

Publication number
EP1660105A1
EP1660105A1 EP03818823A EP03818823A EP1660105A1 EP 1660105 A1 EP1660105 A1 EP 1660105A1 EP 03818823 A EP03818823 A EP 03818823A EP 03818823 A EP03818823 A EP 03818823A EP 1660105 A1 EP1660105 A1 EP 1660105A1
Authority
EP
European Patent Office
Prior art keywords
cells
cancer
treatment
cell
blood cells
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP03818823A
Other languages
German (de)
French (fr)
Inventor
Donnie Rudd
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Regenetech Inc
Original Assignee
Regenetech Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Regenetech Inc filed Critical Regenetech Inc
Publication of EP1660105A1 publication Critical patent/EP1660105A1/en
Withdrawn legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/14—Blood; Artificial blood
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/28—Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/06—Animal cells or tissues; Human cells or tissues
    • C12N5/0602—Vertebrate cells
    • C12N5/0634—Cells from the blood or the immune system
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2501/00—Active agents used in cell culture processes, e.g. differentation
    • C12N2501/10—Growth factors
    • C12N2501/125—Stem cell factor [SCF], c-kit ligand [KL]
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2501/00—Active agents used in cell culture processes, e.g. differentation
    • C12N2501/20—Cytokines; Chemokines
    • C12N2501/22—Colony stimulating factors (G-CSF, GM-CSF)

Definitions

  • the present invention relates to a method of replenishing cells damaged by treatment for cancer.
  • One of the worse side effects of the use of chemotherapy in the treatment for cancer is the loss of energy by the patient due to loss of red blood cells.
  • chemotherapy often causes damage to other rapidly dividing cells, such as the bone m.arrow cens..Bone marrow is responsible for producing red blood cells, white blood cells, and platelets.
  • the reduced activity of the bone marrow is named myelosuppression.
  • Chemotherapy and radiation can depress the number of red blood cells to a low level .and eventually produce tiredness, lack of energy, .and anemia.
  • SCT SC transplantation
  • Fatigue can significantly interfere with a patient's quality of life and may limit the number of chemotherapy cycles that could be a ⁇ ninistered, which may limit the effectiveness of treatment altogether.
  • the preferred treatment for fatigue associated with cancer treatment has been the administration of medication such as epoetin alfa (Procrit), or when the condition becomes severe, a tr-ansfusion of red blood cells.
  • the d.amage by treatment for cancer can be from bone marrow transplantation, chemotherapy, or radiation.
  • the reintroduction of the cells is within a rather short period of time, preferably within one week after the cancer treatment procedure, but should be no later than wittrin one month after the cancer treatment
  • CFU-GM v presertf iny ⁇ units
  • CFU-GEMM CFU-gr ⁇ idocyte-macrophage-erythroid-megakarypcyte
  • BFU-E burst-forming units-erythroid
  • Recombin.ant hematopoietic growth factors have provided the clinician with a useful tool for treating patients with chemotherapy-induced myelosuppression. These factors include myeloid growth factors such as granulocyte colony-stimulating factor (G- CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) which decrease the duration of neutropenia and the incidence of serious infections. It is an object of this invention to provide a method for replenishing cells damaged by treatment for cancer.
  • G- CSF granulocyte colony-stimulating factor
  • GM-CSF granulocyte-macrophage colony-stimulating factor
  • hematopoietic blood cells are removed from a cancer patient prior to chemotherapy treatment.
  • the blood cells are what are currently referred to as pluripotent adult stem cells.
  • the blood cells are placed in a bioreactor, such as that described is United States Patent 5,702,941 which is incorporated herein by reference.
  • the bioreactor vessel is rotated at a speed that provides for suspension of the blood cells to m-aintain their three-dimensional geometry and their cell- to-cell support .and geometry. During the time that the cells are in the reactor, they are fed nutrients .and toxic materials are removed. The cells are expanded to a volume substantially greater than the origin ⁇ cells. The patient is then administered chemotherapy.
  • periphery blood (PB) cells are obtained from normal stem cell (SC) donors.
  • MNCs mononuclear cells
  • each donor Prior to apheresis, each donor is treated with G-CSF 6 :g/kg every 12 hr over 3 days and then once on day 4.
  • MNCs are collected by subjecting each donor's total blood volume to 3 rounds of continuous-flow leukapheresis through a Cobe Spectra cell separator.
  • IMDM Iscove's modified Dulbecco's medium
  • FCS fetal calf serum
  • HA human albumin
  • SCF human stem cell factor
  • IL Deerf ⁇ eld, IL
  • a humidified incubator at 37EC under an atmosphere of 5% CO 2 .
  • the culture bags are inspected daily. On days 2, 5, 6, and 7, each culture is mixed, and a sample is aspirated, counted using the trypan-blue exclusion test. If the concentration of cells in a bag exceeds 0.75 x 10 6 cells/ml, then IMDM supplemented with either 20% FCS, 5% HA or 20% human plasma, 100 ng/ml G-CSF, and 100 ng ml SCF is injected into the bag to adjust the cellular concentration to 0.75 x 10 6 cells/ml.
  • Hematopoietic colony-forming cells are assayed using a modification of a previously described assay.
  • 10 5 MNCs . are cultured in 0.8% methylcellulose with IMDM, 30% FCS, 1.0 U/ml eryihropoietin (Amgen), 50 ng/ml recombinant human GM-CSF (Immunex Corp., Seattle, WA), and 50 ng/ml SCF (Amgen).
  • colonies i defined ast aggregates of more th.an 500 hemoglobinized cells ori 3 or more erythroid subcolonies), for the number of colony-forming units gr.anulocyte-macrophage (CFU-GM) colonies of granulocytic or monocyte-macrophage cells or both, and for the number of CFU-granulocyte-erythroid-macrophage- megakaryocyte (CFU-GEMM) cont.aining all elements. Individual colonies .are plucked from the cultures with a micropipette .and analyzed for cellular composition.
  • CFU-GM colony-forming units
  • CFU-GEMM CFU-granulocyte-erythroid-macrophage- megakaryocyte
  • Lymphocytes are analyzed by 2-color staining using the following antibody combinations: CD56 ⁇ -CD10rPE/CD3 ⁇ FXTC, i CD3rPE/CD4-FITC, CD3-PE/CD8-FITC, CD19-PE. Controls include IgGl-PE/TgGl-FITC for isotype and CD14-PE/CD45-FITC for gating. Progenitor cells are analyzed by 3-color staining with the fmorochromes PerCP/PE/FITC using the following antibody combinations: CD45/CD90/CD34, CD45/CJD34/CD38, CD45/CD34/CD33, and CD45/CD34/CD15. CD45/IgGl/IgGl is

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Biomedical Technology (AREA)
  • Zoology (AREA)
  • Biotechnology (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Immunology (AREA)
  • Cell Biology (AREA)
  • Hematology (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Wood Science & Technology (AREA)
  • Medicinal Chemistry (AREA)
  • Genetics & Genomics (AREA)
  • Developmental Biology & Embryology (AREA)
  • Virology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Epidemiology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Microbiology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Biochemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • Diabetes (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)

Abstract

Disclosed herein is a method of replenishing cells damaged by treatment for cancer. The method comprises removing blood cells from a primate mammal, controllably expanding the cells at a rate which produces an expansion factor of at least 700% within 7 days while maintaining their three-dimensional geometry and their cell-to-cell support and cell-to-cell geometry, removing any toxic materials from the blood cells, and reintroducing the cells into the primate mammal within a time period sufficient to prevent the primate mammal from suffering decreased mobility due to loss of hematopoietic or other cells.

Description

METHOD OF REPLENISHING CELLS DAMAGED BY TREATMENT FOR CANCER Background of the Invention The present invention relates to a method of replenishing cells damaged by treatment for cancer. One of the worse side effects of the use of chemotherapy in the treatment for cancer is the loss of energy by the patient due to loss of red blood cells. In the process of destroying cancer cells, chemotherapy often causes damage to other rapidly dividing cells, such as the bone m.arrow cens..Bone marrow is responsible for producing red blood cells, white blood cells, and platelets. The reduced activity of the bone marrow is named myelosuppression. Chemotherapy and radiation can depress the number of red blood cells to a low level .and eventually produce tiredness, lack of energy, .and anemia. Myelosuppression is the dose-limiting toxicity of most highly effective chemotherapeutic agents. In recent years this limitation has been overcome through the use of SC transplantation (SCT). hi fact, SCT performed after high-dose chemotherapy allows further escalation of dose intensity, thus increasing survival in many patients with advanced malignant dise.ases. Nevertheless, most patients treated with SCT experience prolonged neutropenia .and thrombocytopenia resulting in increased morbidity .and mortality.
Labeled by some as cancer's number one side effect, fatigue is part of the illness of 72% to 95% of patients with cancer. Chronic or acute-some describe it as "hitting a wall"-- he fatigue experienced by patients with cancer differs from that of healthy people. It is debilitating and depressing, it interferes with normal activities, .and it is a barrier to a person's enjoyment of life. The National Cancer Institute describes fatigue's social implications as potentially "profound."
Fatigue, long discounted, has become more prominent because therapies have become more aggressive and exacerbated it and because health professionals have acknowledged it as a dose-limiting toxicity of therapy and as a quantifiable and treatable side effect. It is emerging as a serious topic of rese.arch, which encompasses biochemical, pathophysiologic, psychologic, .and behavioral variables. Unfortunately, while medical science has been making steady progress in treating cancer itself, cancer related fatigue is frequently over-looked, under-recognized and under-treated. Aside from the discomfort of feeling exhausted, fatigue can pose a number of obstacles to coping with cancer and reaping the full benefits of available treatments. Fatigue can significantly interfere with a patient's quality of life and may limit the number of chemotherapy cycles that could be aώninistered, which may limit the effectiveness of treatment altogether. In the past, the preferred treatment for fatigue associated with cancer treatment has been the administration of medication such as epoetin alfa (Procrit), or when the condition becomes severe, a tr-ansfusion of red blood cells.
None of the currently available medications, such as epoetin alfa, provide full relief from fatigue due to chemotherapy. While they assist in reducing some of the problems and providing some relief, the medications also have side effects, which create a new series of problems for the patient. Likewise, a transfusion of red blood cells is generally administered only after the patient has suffered the worst effects of the fatigue. It can therefore be seen that a need exists to minimize the fatigue associated with chemotherapy or radiation for cancer in order to provide a better quality of life for patients undergoing treatment for cancer.
Summary of the Invention
The present invention is a method of replenishing cells damaged by treatment for cancer comprising removing blood cells from a primate mammal, controllably expanding the cells a rate which produces an expansion factor of at least seven times within 7 days while (ain;tain% .the geometry.: an their cell-tp-cell suρport,and . = . cells,, and.. reintroducing the cells into.the primate.mammal within a time period sufficient to prevent the primate mammal from suffering decreased mobility due to loss of hematopoietic or other cells. The d.amage by treatment for cancer can be from bone marrow transplantation, chemotherapy, or radiation. Preferably, the reintroduction of the cells is within a rather short period of time, preferably within one week after the cancer treatment procedure, but should be no later than wittrin one month after the cancer treatment
procedure. ; J thevpresertf iny^^ units (CFU) granulocyte- macropj^age. (CFU-GM) and. of. CFU-gr^idocyte-macrophage-erythroid-megakarypcyte (CFU-GEMM) will increase about 7-fold and about 9-fold, respectively, by day 7 and the number of burst-forming units-erythroid (BFU-E) will increase about 2.7-fold by day 5 of culture. . Significant increases i the numbers of cells expressing CD34+, CD34+^CD3.8+,. CD3.4+/CD33+, .CP34+ CD15+, and CD34+/CD90+ and significant declines in the numbers of cells expressing CD34+/CD38- and CD19 surface antigens will occur. Recombin.ant hematopoietic growth factors have provided the clinician with a useful tool for treating patients with chemotherapy-induced myelosuppression. These factors include myeloid growth factors such as granulocyte colony-stimulating factor (G- CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) which decrease the duration of neutropenia and the incidence of serious infections. It is an object of this invention to provide a method for replenishing cells damaged by treatment for cancer. It is a further object of this invention to provide a method for reducing fatigue in patients being treated for cancer with chemotherapy or radiation. These and still other objects and advantages of the present invention will be app.arent from the description of the preferred embodiments that follow. Detailed Description of the Invention This invention may be more fully described by the preferred embodiment as hereinafter described. In the preferred embodiment of this invention, hematopoietic blood cells are removed from a cancer patient prior to chemotherapy treatment. The blood cells are what are currently referred to as pluripotent adult stem cells. The blood cells are placed in a bioreactor, such as that described is United States Patent 5,702,941 which is incorporated herein by reference. The bioreactor vessel is rotated at a speed that provides for suspension of the blood cells to m-aintain their three-dimensional geometry and their cell- to-cell support .and geometry. During the time that the cells are in the reactor, they are fed nutrients .and toxic materials are removed. The cells are expanded to a volume substantially greater than the origin^ cells. The patient is then administered chemotherapy. In still another embodiment of this invention, periphery blood (PB) cells are obtained from normal stem cell (SC) donors. In brief, mononuclear cells (MNCs) are obtained from the first apheresis product collected from SC donors. Prior to apheresis, each donor is treated with G-CSF 6 :g/kg every 12 hr over 3 days and then once on day 4. MNCs are collected by subjecting each donor's total blood volume to 3 rounds of continuous-flow leukapheresis through a Cobe Spectra cell separator. Operative Method A) Collection and maintenace of cells Collected MNCs (0.75 x 106 cells/ml) are suspended in Iscove's modified Dulbecco's medium (IMDM) (GIBCO, Gr-and Island, NY) supplemented with 20% either fetal calf serum (FCS) (Flow Laboratories, McClean, NA), 5% human albumin (HA) or 20% human plasma, 100 ng ml recombin.ant human G-CSF (Amgen Inc., Thousand Oaks, CA), and 100 ng/ml recombinant human stem cell factor (SCF) (Amgen). The culture mix is injected into 300 ml or 500 ml Life Cell nonpyrogenic plastic bags (Baxter,
Deerfϊeld, IL) and placed in a humidified incubator at 37EC under an atmosphere of 5% CO2. The culture bags are inspected daily. On days 2, 5, 6, and 7, each culture is mixed, and a sample is aspirated, counted using the trypan-blue exclusion test. If the concentration of cells in a bag exceeds 0.75 x 106 cells/ml, then IMDM supplemented with either 20% FCS, 5% HA or 20% human plasma, 100 ng/ml G-CSF, and 100 ng ml SCF is injected into the bag to adjust the cellular concentration to 0.75 x 106 cells/ml. B) Analysis of hematopoietic colony-forming cells Hematopoietic colony-forming cells are assayed using a modification of a previously described assay. In brief, 105 MNCs .are cultured in 0.8% methylcellulose with IMDM, 30% FCS, 1.0 U/ml eryihropoietin (Amgen), 50 ng/ml recombinant human GM-CSF (Immunex Corp., Seattle, WA), and 50 ng/ml SCF (Amgen). One-milliUter aliquots of each culture mixture are then placed in 35-mm Petri dishes (Nunc Inc., Naperville, IL) and incubated in duplicate at 37EC in air in a humidified atmosphere of 5% C02. All cultures are evaluated after 7 days for the number of burst-forming unit- erythrαid (BFU-E). colonies i (defined ast aggregates of more th.an 500 hemoglobinized cells ori 3 or more erythroid subcolonies), for the number of colony-forming units gr.anulocyte-macrophage (CFU-GM) colonies of granulocytic or monocyte-macrophage cells or both, and for the number of CFU-granulocyte-erythroid-macrophage- megakaryocyte (CFU-GEMM) cont.aining all elements. Individual colonies .are plucked from the cultures with a micropipette .and analyzed for cellular composition.
C) Analysis of lymphocytes Lymphocytes are analyzed by 2-color staining using the following antibody combinations: CD56^-CD10rPE/CD3^FXTC, i CD3rPE/CD4-FITC, CD3-PE/CD8-FITC, CD19-PE. Controls include IgGl-PE/TgGl-FITC for isotype and CD14-PE/CD45-FITC for gating. Progenitor cells are analyzed by 3-color staining with the fmorochromes PerCP/PE/FITC using the following antibody combinations: CD45/CD90/CD34, CD45/CJD34/CD38, CD45/CD34/CD33, and CD45/CD34/CD15. CD45/IgGl/IgGl is
used as a control. In brief, 106 cells from each donor are incubated with 10 :1 of
antibodies at 2-8EC for 15 minutes in the dark and then washed twice in phosphate- buffered saline. Then the cells are resuspended, fixed with 1% formaldehyde, and analyzed on a FACScan flow cytometer (Becton-Dickinson) equipped with CELLQuest software (Becton Dickinson). For an.alyses of lymphocytes, 10,000 cells are acquired from each tube, and then gated on the b.asis of the forward and right angle light scatter patterns. The cutoff point is visually set at a level above background positivity exhibited by isotype controls. For analyses of progenitor cells, 75,000 cells from each tube is acquired and then sequentially gated.
D) Increase in hermatopietic colony-forming cells Incubation of the donors' PB cells in my tissue culture system significantly increases the numbers of hematopoietic colony-forming cells. A constant increase in the numbers of CFU-GM (up to 7-fold) and CFU-GEMM (up to 9-fold) colony-forming cells is observed up to day 7 with no clear plateau.
E) Increase in CD34+ cells
Incubation of MNCs from normal donors in my tissue culture system significantly increases the numbers of CD34+ cells. The average number of CD34+ cells increased 10-fold by day 6 of culture and plateaus on that same day. The relative number of CD34+ cells co-expressing the myeloid-lineage makers CD15 and CD33 increases significantly by days 5 and 6. Within one week of the chemotherapy treatment, the expanded cells are reintroduced into the body thereby allowing the body to maintain a sufficient level of replenished cells to overcome the fatigue caused by the chemotherapy. Even though the preferred embodiment of this invention is described above, it will be appreciated by those skilled in the art that other modifications can be made within the scope of this invention.

Claims

What is claimed is: 1. A method of replenishing cells damaged by treatment for cancer comprising removing blood cells from a primate mammal, contrόllably expanding the cells a rate which produces an exp.ansion factor of at least seven times within 7 days while mamtaining their three-dimensional geometry and their cell-to-cell support and cell-to-cell geometry, removing .any toxic materials from the blood cells, and reintroducing the cells into the primate mammal within a time period sufficient to prevent the primate mammal from suffering decreased mobility due to loss of hematopoietic or other cells.
2. A method as in Claim 1 wherein the treatment for cancer is bone marrow tr∑insplantation.
3. A method as is Claim 1 wherein the treatment for cancer is chemotherapy.
4. A method as in Claim 1 wherein the treatment for cancer is radiation.
5. A method as in Claim 1 wherein the reintroduction of the exp.anded blood cells is accomplished within 1 month of the treatment for cancer.
6. A method as in Claim 1 wherein the reintroduction of the exp.anded blood cells is accomplished within 1 week of the treatment for cancer.
7. A method of replenishing cells damaged by treatment for cancer comprising removing peripheal blood cells from a primate mammal, expanding the cells while mamtaining their three-dimensional geometry and their cell-to-cell support and cell-to-cell geometry, removing .any toxic materials from the peripheal blood cells, and reintroducing the cells into the primate mammal within a time period sufficient to prevent the primate mammal from suffering decreased mobility due to loss of hematopoietic or other cells.
8. A method as in Claim 7 wherein the primate mammal is a human.
9. A method as in Claim 7 wherein the treatment for cancer is bone marrow transplantation.
10. A method as is Claim 7 wherein the treatment for cancer is chemotherapy.
11. A method as in Claim 7 wherein the treatment for cancer is radiation.
12. A method as in Claim 7 wherein the reintroduction of the expanded blood cells is accomplished within 1 month of the treatment for cancer.
13. A method as in Claim 7 wherein the reintroduction of the expanded blood cells is accomplished within 1 week of the treatment for cancer.
EP03818823A 2003-09-02 2003-09-02 Method of replenishing cells damaged by treatment for cancer Withdrawn EP1660105A1 (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/US2003/027248 WO2005032566A1 (en) 2003-09-02 2003-09-02 Method of replenishing cells damaged by treatment for cancer

Publications (1)

Publication Number Publication Date
EP1660105A1 true EP1660105A1 (en) 2006-05-31

Family

ID=34421164

Family Applications (1)

Application Number Title Priority Date Filing Date
EP03818823A Withdrawn EP1660105A1 (en) 2003-09-02 2003-09-02 Method of replenishing cells damaged by treatment for cancer

Country Status (6)

Country Link
EP (1) EP1660105A1 (en)
JP (1) JP2007521236A (en)
CN (1) CN1826125A (en)
BR (1) BR0318491A (en)
CA (1) CA2537314A1 (en)
WO (1) WO2005032566A1 (en)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
TWI634949B (en) * 2013-04-23 2018-09-11 獨立行政法人產業技術綜合研究所 Method for producing catalyst for cyclic

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5635387A (en) * 1990-04-23 1997-06-03 Cellpro, Inc. Methods and device for culturing human hematopoietic cells and their precursors
US5199942A (en) * 1991-06-07 1993-04-06 Immunex Corporation Method for improving autologous transplantation
US5277701A (en) * 1991-11-15 1994-01-11 Regents Of The University Of Minnesota Treatment of aluimmunization and refractoriness to platelet transfusion by protein A column therapy
US6436387B1 (en) * 1992-11-24 2002-08-20 G.D. Searle & Co. Methods of ex-vivo expansion of hematopoietic cells using multivariant IL-3 hematopoiesis chimera proteins
DE4240635C2 (en) * 1992-12-03 1997-07-10 Lothar Prof Dr Kanz Multiplication of hematopoietic progenitor cells ex vivo and compositions of hematopoietic growth factors
US5702941A (en) * 1993-09-09 1997-12-30 Synthecon, Inc. Gas permeable bioreactor and method of use
US5599705A (en) * 1993-11-16 1997-02-04 Cameron; Robert B. In vitro method for producing differentiated universally compatible mature human blood cells

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO2005032566A1 *

Also Published As

Publication number Publication date
CA2537314A1 (en) 2005-04-14
CN1826125A (en) 2006-08-30
WO2005032566A1 (en) 2005-04-14
BR0318491A (en) 2006-09-12
JP2007521236A (en) 2007-08-02

Similar Documents

Publication Publication Date Title
Torok-Storb et al. Regulation of in vitro erythropoiesis by normal T cells: evidence for two T-cell subsets with opposing function
Sandstrom et al. Effects of CD34+ cell selection and perfusion on ex vivo expansion of peripheral blood mononuclear cells
Szabolcs et al. Expansion of immunostimulatory dendritic cells among the myeloid progeny of human CD34+ bone marrow precursors cultured with c-kit ligand, granulocyte-macrophage colony-stimulating factor, and TNF-alpha.
JP5543778B2 (en) Methods for producing cell populations
JPH09505462A (en) In vitro proliferation of neutrophil and megakaryocyte progenitor cells in serum-free medium.
JPH08511935A (en) Selective cell growth
Garbe et al. Transforming growth factor‐beta 1 delays formation of granulocyte‐macrophage colony‐forming cells, but spares more primitive progenitors during ex vivo expansion of CD34+ haemopoietic progenitor cells
WO1993012805A1 (en) Methods for regulatory lineages of human hematopoietic cells
Tarella et al. Both early and committed haemopoietic progenitors are more frequent in peripheral blood than in bone marrow during mobilization induced by high‐dose chemotherapy+ G‐CSF
US20040077985A1 (en) Method of replenishing cells damaged by treatment for cancer
Norol et al. Ex vivo expanded mobilized peripheral blood CD34+ cells accelerate haematological recovery in a baboon model of autologous transplantation
US20070172466A1 (en) Method of replenishing cells damaged by treatment for cancer
US20040044300A1 (en) Method of replenishing cells damaged by treatment for cancer
JPH08509859A (en) Expansion of stem cells in long-term bone marrow cultures by neutralization of TGF-β
EP1660105A1 (en) Method of replenishing cells damaged by treatment for cancer
US20040076620A1 (en) Method of repairing primate mammalian tissue
Enokihara et al. Interleukin 2 stimulates the T‐cells from patients with eosinophilia to produce CFU‐Eo growth stimulating factor
Ariyama et al. Synergistic effects of stem cell factor and interleukin 6 or interleukin 11 on the expansion of murine hematopoietic progenitors in liquid suspension culture
Lundell et al. Clinical scale expansion of cryopreserved small volume whole bone marrow aspirates produces sufficient cells for clinical use
MXPA06002378A (en) Method of replenishing cells damaged by treatment for cancer
Smith et al. Neutrophil maturation of CD34+ cells from peripheral blood and bone marrow in serum-free culture medium with PIXY321 and granulocyte-colony stimulating factor (G-CSF)
Roecklein et al. Ex vivo expansion of immature 4-hydroperoxycyclophosphamide-resistant progenitor cells from G-CSF-mobilized peripheral blood
Ogata et al. Effects of interleukin 2 on myelodysplastic syndromes
Estrov et al. Ex vivo expansion of apheresis‐derived peripheral blood hematopoietic progenitors
KR20060085332A (en) Method of replenishing cells damaged by treatment for cancer

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 20060322

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IT LI LU MC NL PT RO SE SI SK TR

DAX Request for extension of the european patent (deleted)
17Q First examination report despatched

Effective date: 20070619

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN

18D Application deemed to be withdrawn

Effective date: 20100622