The General Hospital Corporation

Other

The United States of America As Represented by the Department of Health

Biotransplant, Inc.

David H Sachs

Megan Sykes

Zhirui Wang

Christene A Huang

Scott Arn

J Scott Arn

Joerg Seebach

Harout DerSimonian

Christian LeGuern

Kenth T Gustafsson

Curtis L Cetrulo

Christian A Leguern

Kazuhiko Yamada

Gilles Jf Blancho

Thomas Lorf

Martin Hertl

Manfred W Baetscher

A Benedict Cosimi

Transgenic swine that express human coagulation factors, e.g., human coagulation factor VII, and/or one or more of human coagulation factors II, X and XII, and do not express the corresponding porcine coagulation factor or factors, as well as cells, tissues and organs derived therefrom, and their use in transplantation procedures.

Miniature swine transgenic for one or more coagulation factors

Mutant forms of human CTLA4, and their use, e.g., in xenotransplantation.

Human CTLA4 mutants and use thereof

Methods of preparing and porcine cells, organs and tissues that have reduced immunogenicity, e.g., for transplant into humans, e.g., for the treatment of burn injuries.

Reducing immunogenicity of xenogeneic transplant tissues

IL-2 fusion toxins, e.g., bivalent-IL2 fusion toxins, and methods of use thereof.

Bivalent IL-2 fusion toxins

This invention relates to recombinant CTLA-4 proteins, e.g., soluble CTLA-4 or CTLA-4 fusion toxins, and methods for making and using them.

Recombinant cytotoxic T-lymphocyte-associated protein 4 (CTLA4)

The invention provides a swine which is homozygous for a major histocompatibility complex haplotype and at least 60% homozygous at all other genetic loci and such animal is propagatable, and a cell or an organ derived therefrom. The invention also provides a method for providing a swine which is homozygous at swine leukocyte antigens (SLA) A, B, C, DR, and DQ, and in which at least 60% of all other genetic loci are homozygous, as well as a method of inducing tolerance in a recipient mammal of a first species to a graft from a donor mammal of a second species.

Inbred miniature swine and uses thereof

The invention provides methods for restoring or inducing immunocompetence, the methods including the step of introducing donor thymic tissue into the recipient. The invention also provides methods for inducing tolerance in a recipient including introducing donor thymic tissue into the recipient. The invention further provides methods of inducing tolerance including administering to the recipient a short course of help reducing treatment or administering a short course and methods of prolonging the acceptance of a graft by administering a short course of an immunosuppressant.

Allogeneic and xenogeneic transplantation

Methods of promoting tolerance and inhibiting NK cell mediated attack in a human recipient to a swine graft are disclosed The methods include introducing into the recipient a swine hematopoietic stem cell which has been transformed with a transgene encoding a human MHC class I protein that inhibits recipient NK cell mediated attack.

Transgenic swine & swine cells having human HLA genes

Transgenic swine in which the normal expression of &agr;(1, 3) galactosyltransferase is prevented in at least one organ of tissue type. The absence or inactivation of this enzyme prevents the production of carbohydrate moieties having the distinctive terminal Gal&agr;1-3Gal&bgr;1-4GlcNAc epitope that is a significant factor in xenogeneic, particularly human, transplant rejection of swine grafts.

&agr;(1,3) galactosyltransferase negative porcine cells

In general, the invention features, a method of inducing tolerance in a recipient mammal, e.g., a human, of a first species to a tissue obtained from a mammal, e.g., a swine, e.g., a miniature swine, of a second species, which tissue expresses an MHC antigen, including inserting DNA encoding an MHC antigen of the second species into a bone marrow hematopoietic stem cell from the recipient mammal, and allowing the MHC antigen encoding DNA to be expressed in the recipient.

Specific tolerance in transplantation

The invention features a method designed to lengthen the time an implanted organ (a xenograft) survives in a xenogeneic host prior to rejection. Preparation of the recipient for transplantation includes the following steps: First, the recipient is administered low dose radiation. Second, an antibody preparation that binds T cells and NK cells is injected into the recipient. Third, natural antibodies are absorbed from the recipient's blood by hemoperfusion of an organ of the donor species. Fourth, hematopoietic stromal tissue of the donor species is administered to the recipient. Fifth, donor hematopoietic stem cells are injected into the recipient. Finally, the xenograft organ is implanted into the recipient mammal. Best results are obtained when all steps are used in combination.

Induced tolerance to xenografts

Transgenic swine in which the normal expression of .alpha.(1,3) galactosyltransferase is prevented in at least one organ of tissue type. The absence or inactivation of this enzyme prevents the production of carbohydrate moieties having the distinctive terminal Gal.alpha.1-3Gal.beta.1-4GlcNAc epitope that is a significant factor in xenogeneic, particularly human, transplant rejection of swine grafts.

.alpha.(1,3) galactosyltransferase negative porcine cells

A genetically engineered swine cell having a transgene encoding a human HLA protein.

Transgenic swine and swine cells having human HLA genes

Methods of inducing tolerance including administering to the recipient a short course of help reducing treatment or administering a short course and methods of prolonging the acceptance of a graft by administering a short course of an immunosuppressant.

Growing community of inventors

Newton, MA, United States of America

David H Sachs