Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai
Patent
1998-04-10
2000-08-15
Moezie, F. T.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Peptide containing doai
435 695, 4352401, 4353201, 435243, 435 2, 435354, 435366, 424529, 47 6, 514 2, 514 21, 600 36, 600 37, A61F 204, C12P 2102, A61K 3514
Patent
active
061036943
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to the field of improving the engraftment of hematopoietic stem and progenitor cells in human recipients to treat disease. The invention also relates to a method for decreasing radiation or chemotherapy for hematopoietic pluripotent cell engraftment.
2. Background Art
The practice of bone marrow transplantation (BMT) or peripheral blood stem cell transplantation (PBSCT) involves placing a suspension of donor hematopoietic pluripotent cells (HPCs) into the blood stream of the recipient. HPC transplantations are currently performed with a recipient pre-conditioning regimen of high dosage radiation and/or chemotherapy. The goal of these treatments is to create an environment in the recipient in which the donor's HPCs can successfully engraft by homing into the recipient's bone marrow to further undergo hematopoiesis. There may be several objectives for the use of such pre-conditioning regimens, including eliminating cells underlying diseases such as leukemia, or lymphoma, or serving an immunosuppressive function to mitigate graft rejection in the treatment of non-cancerous diseases. Conditioning regimens overall have the desirable effect of eradicating endogenous HPCs to make available more homing sites for transplanted HPCs to successfully engraft. It is believed that current radiation treatments allow homing and engraftment of transplanted stem cells by directly damaging or depleting the recipient's own stem cells, other hematopoietic regulatory cells, bone marrow stroma, and/or the microcirculatory system. Tavassoli, M., "The role of conditioning regimens in homing of transplanted hemopoietic cell," Bone Marrow Transplantion, 10: 15-17 (1992).
In clinical practice, radiation has been used primarily in high doses to eliminate cells underlying cancerous diseases and to immunosuppress graft rejection. Currently, patients are irradiated with approximately 500 to 1600 cGy at single doses or in fractions. However, the use of radiation can have lethal toxic effects in the recipient, due to the depletion of mature functional blood cells and damage to other organ systems. Therefore, non-myeloablative pre-transplantation regimens, which both minimize radiation effects and attain effective levels of engraftment, are very desirable.
SUMMARY OF THE INVENTION
The present invention provides a method of engrafting donor mammalian hematopoietic pluripotent cells in a mammalian recipient using a decreased amount of radiation, comprising: a. administering to the recipient at least one dosage of a hematopoietic growth factor; b. subjecting the recipient to a low dosage of radiation; and, c. transplanting the donor hematopoietic pluripotent cells into the recipient, thereby engrafting the donor mammalian hematopoietic pluripotent cells in the mammalian recipient using a decreased amount of radiation.
The invention also provides a method of engrafting donor mammalian hematopoietic pluripotent cells in a mammalian recipient using a decreased amount of radiomimetic compound, comprising: a. administering to the recipient at least one dosage of a hematopoietic growth factor; b. subjecting the recipient to a low dosage of radio-mimetic compound; and, c. transplanting the hematopoietic pluripotent cells into the recipient, thereby engrafting the donor mammalian hematopoietic pluripotent cells in the mammalian recipient using a decreased amount of radio-mimetic compound .
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a bar graph showing the cytokine hematopoietic growth factor pre-treatment conditioning effect on engraftment of HPCs following 200 cGy radiation in mice, one month after transplantation. Recipient C57BL/6J-Ly-5.1-Pep.sup.3b mice received b.i.d. sc injections of PBS (.quadrature.) 0.1% BSA, 4 .mu.g rhGCSF (.quadrature.) in 0.1% BSA, or 4 .mu.g rhGCSF plus 1.0 .mu.g rmSCF(.box-solid.) in 0.1% BSA (R&D Systems, Minneapolis, Minn.) for four days. On the fifth day, mice received a single sc injection followed one hour later by a 200 cGy r
REFERENCES:
patent: 5004681 (1991-04-01), Boyse et al.
patent: 5078996 (1992-01-01), Conlon, III et al.
patent: 5106733 (1992-04-01), Baker et al.
Down et al., "Transient and permanent engraftment potential of murine hematopoietic stem cell subsets: differential effects of host conditioning with gamma radiation and cytotoxic drugs," Exp. Hem. 21:913-921(1993).
Tavassoli, M., "The role of conditioning regimens in homing of transplanted hemopoietic cell," Bone Marrow Transplantation 10:15-17(1992).
Mauch, P. et al., "Hematopoietic stem cell compartment: acute and late effects of radiation therapy and chemotherapy," Int. J. Radiation Oncology Biol. Phys., 31(5): 1319-1339 (1995).
Uckun, F. et al., "in vivo radioprotective effects of recombinant human granulocyte colony-stimulating factor in lethally irradiated mice," Blood, 75:638-645 (1990).
Weaver, C.H. et al., "Phase I study of high-dose busulfan, melphalan and thiotepa with autologous stem cell support in patients with refractory malignancies," Bone Marrow Transplantation, 14:813-819 (1994).
Faucher, C. et al., "Comparison of G-CSF-primed peripheral blood progenitor cells and bone marrow auto transplantation: clinical assessment and cost-effectiveness," Bone Marrow Transplantation, 14:895-901 (1994).
Vose, J.M. et al. "Clinical applications of hematopoietic growth factors," J. Clin. Oncology, 13(4): 1023-1035 (1995).
Wilson et al., "Interleukin-I administration before high-dose ifosamide (I), CBDCA (C), and etoposide (E) (ICE) with autologous bone marrow shortens neutrophil recovery: a phase I/II study," Proc. Am. Soc. Clin. Oncol., 12: 937a (1993).
Talmadge, J.E., "The combination of stem cell transplantation and immunotherapy: future potential," In vivo, 8:675-690 (1994).
Juttner, C.A. et al., "Blood cell transplantation: report from an international consensus meeting," Bone Marrow Transplantation, 14:689-693 (1994).
George, M. J., "The present and future of hematopoietic cytokines in clinical practice," Polyfunctionality of Hematopoietic Regulators: The Metcalf Forum. STEM CELLS, 12(supp I): 249-255 (1994).
Nemunaitis, J., "Biological activities of hematopoietic growth factors that lead to future clinical application," Cancer Investigation, 12(5): 516-529 (1994).
Sheridan et al., The Lancet, 339, 640-644 (1992).
Moore et al., Proc. Natl. Acad. Sci. USA, 84, 7134-7138 (1987).
Rosenzweig et al. "Efficient and Durable Gene Marking of Hematopoietic Progenitor Cells in Nonhuman Primates After Non-ablatine Conditioning" Blood. pp. 1-44, 1999.
Manual of Oncology Therapeutics, Ed See-Lasley, The C.V. Masly Co., St. Louis, pp. 17,88,104. 1981.
Malech Harry L.
Mardiney, III Michael
Moezie F. T.
The United States of America as represented by the Department of
LandOfFree
Method of decreasing radiation of radio-mimetic chemotherapy for does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Method of decreasing radiation of radio-mimetic chemotherapy for, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Method of decreasing radiation of radio-mimetic chemotherapy for will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2006899