Abstract: Antibody-mediated xenograft rejection is attenuated by (1) removing preformed antibodies to various identified carbohydrate xenoantigens from the recipient's circulation prior to transplantation by extracorporeal perfusion of the recipient's blood over a biocompatible solid support to which the xenoantigens are bound and/or (2) parenterally administering a xenoantibody-inhibiting amount of an identified xenoantigen to the recipient shortly before graft revascularization and thereafter.
Type:
Grant
Filed:
June 2, 1995
Date of Patent:
August 19, 2003
Assignees:
Alberta Research Council, Integris Baptist Medical Center, Inc.
Inventors:
A. Heather Good, David K.C. Cooper, Andrew J. Malcolm
Abstract: Methods to manipulate animals such as pigs, and the animals and tissues thereby derived, to reduce their immunogenicity following implantation into humans, are described. These methods are based on the discovery that certain carbohydrate structures on pig tissues, which require expression of the gene encoding the &agr; 1→3 galactosyl transferase enzyme, are targets for natural preformed antibodies of humans and elicit further antibody production in humans, while other carbohydrate structures do not or do so in a reduced amount. In the preferred embodiment, animals are produced by homologous recombination of the gene encoding &agr; 1→3 galactosyl transferase in embryonic stem cells or by microinjection into embryos of sequences eliminating or decreasing expression of &agr; 1→3 galactosyl transferase. In alternative embodiments, animals are produced having reduced amounts of →1→3 galactosyl epitopes or epitopes which are masked by sialylation or fucosylation.
Abstract: Methods to manipulate animals such as pigs, and the animals and tissues thereby derived, to reduce their immunogenicity following implantation into humans, are described. These methods are based on the discovery that certain carbohydrate structures on pig tissues, which require expression of the gene encoding the &agr; 1→3 galactosyl transferase enzyme, are targets for natural preformed antibodies of humans and elicit further antibody production in humans, while other carbohydrate structures do not or do so in a reduced amount. In the preferred embodiment, animals are produced by homologous recombination of the gene encoding &agr; 1→3 galactosyl transferase in embryonic stem cells or by microinjection into embryos of sequences eliminating or decreasing expression of &agr; 1→3 galactosyl transferase. In alternative embodiments, animals are produced having reduced amounts of &agr; 1→3 galactosyl epitopes or epitopes which are masked by sialylation or fucosylation.
Type:
Grant
Filed:
January 27, 1995
Date of Patent:
December 18, 2001
Assignees:
Integris Baptist Medical Center, Inc., Oklahoma Medical Research Foundation
Abstract: Antibody-mediated xenograft rejection is attenuated by (1) removing preformed antibodies to various identified carbohydrate xenoantigens from the recipient's circulation prior to transplantation by extracorporeal perfusion of the recipient's blood over a biocompatible solid support to which the xenoantigens are bound and/or (2) parenterally administering a xenoantibody-inhibiting amount of an identified xenoantigen to the recipient shortly before graft revascularization and thereafter.
Type:
Grant
Filed:
September 23, 1997
Date of Patent:
November 2, 1999
Assignees:
Alberta Research Council Edmonton, Integris Baptist Medical Center, Inc.
Inventors:
A. Heather Good, David K.C. Cooper, Andrew J. Malcolm
Abstract: Antibody-mediated xenograft rejection is attenuated by parenterally administering a xenoantibody-inhibiting amount of an identified carbohydrate xenoantigen to the recipient shortly before graft revascularization and thereafter.
Type:
Grant
Filed:
June 2, 1995
Date of Patent:
June 16, 1998
Assignees:
Alberta Research Council, INTEGRIS Baptist Medical Center, Inc.
Inventors:
A. Heather Good, David K. C. Cooper, Andrew J. Malcolm
Abstract: Antibodies directed against idiotypes on naturally occurring human anti-animal antibodies are disclosed for use in inhibiting xenograft rejection in human patients. An effective quantity of these anti-idiotypic antibodies is injected into the actual or potential xenograft recipient in order to bind to the idiotypes expressed on anti-animal antibodies as well as subpopulations of B lymphocytes, to inhibit hyperacute rejection of transplanted animal tissues or organs by the human patient. Alternatively, anti-idiotypic antibodies are used in the form of immunoaffinity columns to deplete anti-animal antibodies from the recipient's serum. Methods of making mouse monoclonal, mouse recombinant, and human recombinant anti-idiotypic antibodies are described, as well as immunoaffinity columns containing immobilized anti-idiotypic antibodies.
Type:
Grant
Filed:
October 12, 1993
Date of Patent:
October 1, 1996
Assignees:
Oklahoma Medical Research Foundation, Integris Baptist Medical Center, Inc.