Other

University of Pennsylvania

Crosscart, Inc.

Rush University

Uri Galili

Kevin R Stone

Patricia M Repik

A method for preparing a soft tissue xenograft includes the steps of removing at least a portion of a soft tissue from a non-human animal to provide a xenograft; washing the xenograft in saline and alcohol; subjecting the xenograft to cellular disruption treatment; and either digesting the xenograft with a glycosidase or glycosidase digestion followed by treatment for sialylation. A soft tissue xenograft for implantation into a human includes a portion of a soft tissue from a non-human animal, wherein the portion has extracellular matrix and substantially only dead cells. The matrix and dead cells have substantially no surface &agr;-galactosyl moieties and have sialic acid molecules linked to at least a portion of surface carbohydrate moieties. Each of the xenografts of the invention has substantially the same mechanical properties as a corresponding native soft tissue.

Soft tissue xenografts

Toxin complexes and methods for preventing immune rejection of xenografts are provided. Cell toxins are coupled to carriers that display ligands which allow the complex to be recognized by antigen binding sites (i.e., specific B cell and T cell receptors) on the lymphocytes as the target cells responsible for the specific immune response. The toxin complexes interact with the specific receptors (antigen binding sites) on lymphocytes, and are internalized by these target cells. Once internalized, the toxin complex dissociates to release the cell toxin, which destroys the target cell. In one embodiment, the target cells are B lymphocytes and T lymphocytes, the antigen binding sites are anti-Gal B cell receptors and T cell receptors which interact with &agr;-gal epitopes displayed on an &agr;1-acid glycoprotein carrier. In other embodiments, the toxin complex is directed by the corresponding ligands to target cells responsible for autoimmune diseases in which the specificity of the autoantibodies is defined.

Methods and compositions for preventing anti-Gal production in xenograft recipients

The invention encompasses methods and compositions for inducing an immune response in an anti-Gal synthesizing animal including viral and tumor antigens manipulated to express &agr;-galactosyl epitopes.

Compositions and methods for vaccines comprising &agr;-galactosyl epitopes

The invention provides a substantially non-immunogenic ligament or tendon xenograft for implantation into humans. The invention further provides a method for preparing a ligament xenograft by removing at least a portion of a ligament from a non-human animal to provide a xenograft; washing the xenograft in saline and alcohol; subjecting the xenograft cellular disruption treatment, such as exposure to ultraviolet radiation, immersion in alcohol, ozonation, freeze/thaw cycling, and optionally chemical crosslinking. In addition to or in lieu of the above treatments, the methods include digestion of the carbohydrate moieties of the xenograft with a glycosidase, preferably in a range of about 1 mU/ml to about 1000 U/ml, followed by treatment for sialylation. The invention also provides articles of manufacture produced by one or more of the above-identified methods of the invention. The invention further provides a ligament xenograft for implantation into a human including a portion of a ligament from a non-human animal, wherein the portion includes extracellular components and substantially only dead cells having substantially no surface &agr;-galactosyl moieties and having sialic acid linked to at least a portion of surface carbohydrate moieties. Each of the xenografts of the invention is substantially non-immunogenic and has substantially the same mechanical properties as the respective native ligament.

Anterior cruciate ligament xenografts

The invention provides an article of manufacture comprising a substantially non-immunogenic articular cartilage xenograft for implantation into humans. The invention further provides a method for preparing an articular cartilage xenograft by removing at least a portion of an articular cartilage from a non-human animal to provide a xenograft; washing the xenograft in saline and alcohol; subjecting the xenograft to at least one treatment selected from the group consisting of exposure to ultraviolet radiation, immersion in alcohol, ozonation, freeze/thaw cycling, and optionally to chemical crosslinking. In addition to or in lieu of the above treatments, the methods include a cellular disruption treatment and either digestion of the carbohydrate moieties of the xenograft with a glycosidase in a range of about 1 mU/ml to about 1000 U/ml or glycosidase digestion followed by treatment for sialylation. The invention also provides articles of manufacture produced by one or more of the above-identified methods of the invention. The invention further provides an articular cartilage xenograft for implantation into a human including a portion of an articular cartilage from a non-human animal, wherein the portion includes extracellular matrix and substantially only dead cells. The matrix and dead cells have substantially no surface .alpha.-galactosyl moieties and have sialic acid linked to at least a portion of surface carbohydrate moieties. Each of the xenografts of the invention is substantially non-immunogenic and has substantially the same mechanical properties as the respective native articular cartilage.

Articular cartilage xenografts

The invention provides an article of manufacture comprising a substantially non-immunogenic knee meniscal xenograft for implantation into humans. The invention further provides methods for preparing a knee meniscal xenograft by removing at least a portion of a meniscus from a non-human animal to provide a xenograft; washing the xenograft in saline and alcohol; and subjecting the xenograft to at least one treatment selected from the group consisting of exposure to ultraviolet radiation, immersion in alcohol, ozonation, and freeze/thaw cycling. In addition to or in lieu of the above treatments, the methods include a cellular disruption treatment and either digestion of the carbohydrate moieties of the xenograft with a glycosidase in a range of about 1 mU/ml to about 1000 U/ml or glycosidase digestion followed by treatment for sialylation. The invention also provides articles of manufacture produced by one or more of the above-identified methods of the invention. The invention further provides a meniscal xenograft for implantation into a human including a portion of a meniscus from a non-human animal, wherein the portion includes extracellular matrix and substantially only dead cells. The matrix and dead cells have substantially no surface .alpha.-galactosyl moieties and have sialic acid molecules linked to at least a portion of surface carbohydrate moieties. Each of the xenografts of the invention is substantially non-immunogenic and has substantially the same mechanical properties as the respective native meniscus.

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Chicago, IL, United States of America

Uri Galili