Classifications

• • 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
  • C12N5/0647—Haematopoietic stem cells; Uncommitted or multipotent progenitors
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K31/00—Medicinal preparations containing organic active ingredients
  • A61K31/33—Heterocyclic compounds
  • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
  • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
  • A61K31/47—Quinolines; Isoquinolines
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K31/00—Medicinal preparations containing organic active ingredients
  • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
• • 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
  • A61K35/22—Urine; Urinary tract, e.g. kidney or bladder; Intraglomerular mesangial cells; Renal mesenchymal cells; Adrenal gland
• • 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
  • 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
  • A61K35/37—Digestive system
  • A61K35/407—Liver; Hepatocytes
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K38/00—Medicinal preparations containing peptides
  • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
  • A61K38/08—Peptides having 5 to 11 amino acids
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K39/00—Medicinal preparations containing antigens or antibodies
  • A61K39/0005—Vertebrate antigens
  • A61K39/001—Preparations to induce tolerance to non-self, e.g. prior to transplantation
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P37/00—Drugs for immunological or allergic disorders
  • A61P37/02—Immunomodulators
  • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection

Definitions

• one or more of the administrations can include a number of donor hematopoietic cells which is at least twice, is equal to, or is at least 75, 50, or 25% as great as, the number of bone marrow cells found in an adult of the recipient species; include a number of donor hematopoietic stem cells which is at least twice, is equal to, or is at least 75, 50, or 25% as great as, the number of bone marrow hematopoietic stem cells found in an adult of the recipient species.
• This method can be practiced without the administration of hematopoietic space- creating irradiation, e.g., whole body irradiation.
• Whole body irradiation is often used in the art to create hematopoietic space and thus promote engraftment, chimerism, and tolerance.
• the need for hematopoietic space-creating irradiation can be reduced or entirely eliminated by inclusion of one or more of the following steps in the method:
• Help reducing agent is an agent, e.g., an immunosuppressive drug, which results in the reduction of cytokine release.
• help reducing agents are cyclosporine, FK-506, and rapamycin.
• Anti-T cell antibodies because they can eliminate T cells, are not preferred for use as help reducing agents.
• a help reducing agent must be administered in sufficient dose to give the level of inhibition of cytokine release which will result in tolerance.
• the help reducing agent should be administered in the absence of treatments which promote cytokine, e.g., IL-2, release.
• Fig. 1 is a depiction of multilineage analysis of donor repopulation in animals administered either one injection ( — ) or five injections ( ) of BMC.
• mice were evaluated for myelosuppression. Complete blood counts were determined on days -1 , 1, 3, 6, 8, 10, 13, and 20 for animals receiving TI on day 0 with or without mAb treatments, without BMT. In recipients of TI ⁇ mAbs, average WBC counts reached a nadir of .3,000/ ⁇ l on day 1 , and returned to normal by day 8. The lowest level reached in any individual mouse was 2,600/ ⁇ l. Neither platelet counts nor hemoglobin concentrations decreased significantly at any time in any group. All animals survived with no clinical toxicity. Therefore, host conditioning with mAbs/TI does not cause clinically significant myelosuppression or toxicity, yet permits PGHSC engraftment from high-dose allogeneic marrow.
• ATG is superior to anti-NK monoclonal antibodies, as the latter are generally not lytic to all host NK cells, while the polyclonal mixture in ATG is capable of lysing all host NK cells.
• Anti-NK monoclonal antibodies can, however, be used.
• fetal liver can also serve as an alternative to bone marrow as a source of hematopoietic stem cells.
• the thymus is the major site of T cell maturation.
• Each organ includes an organ specific stromal matrix that can support differentiation of the respective undifferentiated stem cells implanted into the host.
• adult thymus may be used, fetal tissue obtained sufficiently early in gestation is preferred because it is free from mature T lymphocytes which can cause GVHD. Fetal tissues also tend to survive better than adult tissues when transplanted.
• Methods of preparing the recipient for transplant of hematopoietic stem cells may be varied. For instance, recipient may undergo a splenectomy. The latter would preferably be administered prior to the non-myeloablative regimen, e.g., at day -14.

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• Health & Medical Sciences (AREA)
• Life Sciences & Earth Sciences (AREA)
• Chemical & Material Sciences (AREA)
• Engineering & Computer Science (AREA)
• General Health & Medical Sciences (AREA)
• Immunology (AREA)
• Medicinal Chemistry (AREA)
• Veterinary Medicine (AREA)
• Public Health (AREA)
• Pharmacology & Pharmacy (AREA)
• Animal Behavior & Ethology (AREA)
• Epidemiology (AREA)
• Biomedical Technology (AREA)
• Cell Biology (AREA)
• Zoology (AREA)
• Biotechnology (AREA)
• Developmental Biology & Embryology (AREA)
• Bioinformatics & Cheminformatics (AREA)
• Virology (AREA)
• Hematology (AREA)
• Organic Chemistry (AREA)
• Wood Science & Technology (AREA)
• Genetics & Genomics (AREA)
• Microbiology (AREA)
• Transplantation (AREA)
• Proteomics, Peptides & Aminoacids (AREA)
• Gastroenterology & Hepatology (AREA)
• General Engineering & Computer Science (AREA)
• Urology & Nephrology (AREA)
• Physiology (AREA)
• Mycology (AREA)
• Nutrition Science (AREA)
• Biochemistry (AREA)
• General Chemical & Material Sciences (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• Chemical Kinetics & Catalysis (AREA)
• Medicines Containing Material From Animals Or Micro-Organisms (AREA)
• Inks, Pencil-Leads, Or Crayons (AREA)
• Gloves (AREA)
• Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

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• 1997
  • 1997-05-08 EP EP97926433A patent/EP0918524A4/en not_active Withdrawn
  • 1997-05-08 JP JP09540229A patent/JP2000511888A/ja not_active Ceased
  • 1997-05-08 WO PCT/US1997/007874 patent/WO1997041863A1/en not_active Ceased
  • 1997-05-08 AU AU31203/97A patent/AU734665B2/en not_active Ceased
  • 1997-05-08 ES ES00114769T patent/ES2201977T3/es not_active Expired - Lifetime
  • 1997-05-08 CA CA002253597A patent/CA2253597A1/en not_active Abandoned
  • 1997-05-08 DE DE69723888T patent/DE69723888T2/de not_active Expired - Fee Related
  • 1997-05-08 US US08/855,705 patent/US6006752A/en not_active Expired - Lifetime
  • 1997-05-08 AT AT00114769T patent/ATE245990T1/de not_active IP Right Cessation
• 1999
  • 1999-08-13 US US09/374,498 patent/US6412492B1/en not_active Expired - Lifetime
• 2002
  • 2002-05-24 US US10/155,878 patent/US6718986B2/en not_active Expired - Lifetime
• 2003
  • 2003-10-29 US US10/696,127 patent/US6877514B2/en not_active Expired - Lifetime

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