Drug – bio-affecting and body treating compositions – Whole live micro-organism – cell – or virus containing – Genetically modified micro-organism – cell – or virus
Patent
1995-06-06
2000-05-09
Crouch, Deborah
Drug, bio-affecting and body treating compositions
Whole live micro-organism, cell, or virus containing
Genetically modified micro-organism, cell, or virus
424 933, 424577, 800 8, 435 11, A61K 4800, C12N 1500, A01N 102
Patent
active
060600497
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
1. Field of the Invention
The field of the present invention relates to the transplanting of organs and tissues, and more particularly to the production in a surrogate of regulatory cells and factors capable of generating immune tolerance to a graft organ in the recipient and to subsequently transplanting xenografts from the surrogate to a recipient. The invention also relates to methods for producing within a surrogate, organs for transplant that are repopulated with cells from the organ graft recipient, lessening the antigen difference and therefore the risk of rejection.
2. Review Of The Related Art
The normal immune system is capable of specifically differentiating between "self" and foreign entities, with foreign entities including infectious agents. The ability to differentiate self from foreign entities is established naturally during fetal development, when the developing immune system of the fetus is programmed to recognize presented antigens as self; i.e. as antigens of the fetus. Several mechanisms are responsible for immune tolerance; including suppression, negative selection, and anergy. Suppression refers to the inhibition of lymphocytes that are reactive to self antigens. Negative selection refers to prevention of the development of immune clones capable of reacting with self antigens. Anergy refers to cells that recognize self but fail to proliferate or function in response to the self antigen.
Suppressor and regulatory T cells block the proliferation of self-reactive lymphoid cells, usually through the secretion of soluble factors. Upon recognition by a self-reactive precursor T cell, the self-reactive cells are suppressed. A network of antibodies and T cell receptors may develop the capability to react against the reactive components of self-reactive antibodies and T cells receptors, with the network of antibodies and T cell receptors also known as an anti-idiotype network. The antibodies and T cell receptors then neutralize self-reactive cells. Veto cells are T cells that express a self antigen.
The principal problems associated with organ transplantation are immune rejection and a shortage of acceptable donors. Unless the donor is an identical twin, the immune system of the recipient recognizes the graft as foreign and the recipient's immune system tries to reject the graft. Although immune suppression may postpone rejection for prolonged periods, immune suppression places the recipient at risk for infections and malignancies. Despite requiring chronic immune suppression, most organ and tissue transplants are successful in saving lives and improving the quality of life. The list of successfully transplanted tissues includes: kidney, heart, lung, liver, corneas, pancreas, pancreatic islets of Langerhans, intestines, brain tissue, liver, spleen, thymus, lymph nodes, bone marrow, skin, and bones. Combinations of tissue have also been transplanted; for example, heart-lung transplants, pancreas-kidney transplants, and pancreas-kidney-intestinal transplants.
Because of the relative success of the above organ and tissue transplants, a marked shortage of human organ donors exists. For example, although nearly 9,500 kidney transplants are performed annually in the United States, approximately 40,000 Americans develop end stage renal disease annually, and these 40,000 Americans could benefit from organ transplants. Xenografts, herein defined as transplants from another species, could potentially resolve the shortage of transplantable organs and tissues, but the risk of rejection is considered to be even greater than for allografts, herein defined as transplants from a non-identical donor of the same species.
Because of the severe shortage of human organ donors, transplant recipients have occasionally received a xenograft for short term life support, with the short term xenograft also referred to as a bridge transplant. By using bridge transplants of xenografts, additional time is provided to locate a suitable human donor.
Immune tolerance for new transplant grafts has
REFERENCES:
patent: 4400376 (1983-08-01), Sanderson
patent: 4406885 (1983-09-01), Pinter
patent: 4448765 (1984-05-01), Ash et al.
patent: 4624917 (1986-11-01), Sugimoto
patent: 5004681 (1991-04-01), Boyse et al.
patent: 5061620 (1991-10-01), Tsukamoto et al.
Herzog et al., Suppression and Contrasuppression in Athymic Nude Mice: Nude Mice Produce the Antigen Specific Component of a T Suppressor Factor that Inhibits the Late 24-hr Phase of DTH, but Do Not Generate Suppression nor Contrasuppression of the Early Initiating Phase of DTH; Cell Immunology 127, 130-145 (1990).
Chen et al., Transplantation Tolerance: Evidence for Lyt+, 2-, Qa 1.2+ Suppressor-Inducer T Cells in Allogeneic Thymus-Grafted Nude Mice; Cell Immunology 77, 318 (1983).
Miller et al., An Immunological Suppressor Cell Inactivating Cytotoxic T-Lymphocyte Precursor Cells Recognizing It, Nature 287, 544 (1980).
Simpson et al., Mice with the xid Mutation Lack the Regulatory Antibodies that are Necessary for the Induction of Contrasuppression, Cell Immunology 164, 126 (1995).
Rosenkrantz et al., Both Ongoing Suppression and Clonal Elimination Contribute to Graft-Host Tolerance After Transplantation of HLA Mismatched T Cell-Depleted Marrow for Severe Combined Immunodeficiency; Journal of Immunology 144, 1721 (1990).
Asseman et al., Interleukin 10 is a Growth Factor for a Population of Regulatory T Cells; Gut 42, 157 (1998).
Gebel, et al., Characterization of Circulating Suppressor T Lymphocytes in Bone Marrow Transplant Recipients; Transplantation 43, 258 (1987).
Kunicaka, et al., Induction of Suppressor Cells to T-and B-Cell Proliferative Responses and Immunoglobulin Production by Monoclonal Antibodies Recognizing the CD3 T-Cell Differentiation Antigen, Cellular Immunology 116, 195 (1988).
Knulst, et al., Prevention of Lethal Graft-Versus-Host Disease in Mice by Monoclonal Antibodies Directed Against T Cells or Their Subsets. II. Evidence for the Induction of a State of Tolerance Based on Suppression; Bone Marrow Transplantation 13, 293 (1994).
Gianello, et al., Tolerance to Class I-Disparate Renal Allografts in Miniature Swine; Transplantation 59, 772 (1995).
Deeg, et al., Specific Tolerance and Immunocompetence in Haploidentical, but not in Completely Allogeneic, Canine Chimeras Treated with Methotrexate and Cyclosporine; Transplantation 44, 621 (1987).
Shen, et al., Suppressor Cells and Intrathymic Inoculation of Donor Alloantigens in Cardiac Transplantation; Society of Thoracic Surgeons, 1683 (1995).
Shimomura et al., Tolerance Induction to Cardiac Allografts by Simultaneous or Sequential Intrathymic Inoculation of Disparate Alloantigens; Transplantation 60, 806 (1995).
Rieger et al., Induction of Suppressor Cell Mechanism in Antilymphocyte Serum-Induced Skin Allograft Tolerance in Mice; Folia Biology 25 (Praha), 220 (1979).
Sanada et al., Establishment of Chimerism in Donor Liver with Recipient-Type Bone Marrow Cells Prior to Liver Transplantation Produces Marked Suppression of Allograft Rejection in Rats; Transplantation Int 11, S174 (1998).
Qian, et al., Intrathymic Tolerance and Age; Transplantation Proceedings 27, 3391, (1995).
Database Medline, Abstract 82224968 and Transplantation 33(5):510-514 (May 1982).
Proceedings of "Xenograft 25," M. A. Hardy (ed.), Elsevier, 1989.
Alexandre, et al., "Present Experiences in a Series of 26 ABO-Incompatible Living Donor Renal Allografts," Transplantation Proceedings, 19:4538-4532 (1987).
Auchincloss, Hugh, Jr., "Xenogeneic Transplantation," Transplantation, 46:1-20 (1988).
Drugan, et al., "Fetal Organ and Xenograft Transplantation," Am. J. Obstet. Gynecol., 160:289-293 (1989).
Platt, et al., "Discordant Xenografting: Challenges and Controversies," Current Opinion in Immunology, 3:735-739 (1991).
Crombleholme, et al., "Transplantation of Fetal Cells," Am. J. Obstet. Gynecol., 164:218-230 (1991).
Zanjani, et al., "Hematopoietic Chimerism in Sheep and Nonhuman Primates by in Utero Transplantation of Fetal Hematopoietic Stem Cells," Blood Cells, 17:349
Beckerleg Anne Marie S.
Crouch Deborah
Ximerex, Inc.
LandOfFree
Surrogate tolerogenesis for the development of tolerance to xeno does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Surrogate tolerogenesis for the development of tolerance to xeno, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Surrogate tolerogenesis for the development of tolerance to xeno will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-1061940