Materials and methods for altering an immune response to exogenous and endogenous immunogens, including syngeneic and non-syngeneic cells, tissues or organs

Abstract

Disclosed herein are materials and methods for modulating an immunologically adverse response to an exogenous or endogenous immunogen, including a cell, tissue, or organ associated immunogen. An implantable material comprising cells, such as but not limited to endothelial cells, anchored or embedded in a biocompatible matrix can modulate an adverse immune or inflammatory reaction to exogenous or endogenous immunogens, including response to non-syngeneic or syngeneic cells, tissues or organs, exogenous immunogens or stimuli, as well as ameliorate an autoimmune condition. The implantable material can be provided prior to, coincident with, or subsequent to occurrence of the immune response or inflammatory reaction. The implantable material can induce immunological acceptance in a transplant patient, reduce graft rejection and reduce donor antigen immunogenicity.

Description

FIELD OF THE INVENTION[0001]This invention is directed to materials and methods for modulating an immunologically adverse response to an exogenous or endogenous immunogen, including a cell-, tissue-, or organ-associated immunogen. For example, the present invention can modulate an adverse immune response or inflammatory reaction to exogenous or endogenous immunogens, including non-syngeneic or syngeneic cells, tissues or organs, as well as ameliorate an autoimmune condition.BACKGROUND OF THE INVENTION[0002]Research on xenotransplantation has been intensified over the past years to alleviate organ shortage. However, host immune responses present a formidable barrier to transplantation across species. Whereas natural antibodies cause immediate rejection of such discordant transplants, endothelial cell (EC) injury and activation of graft vessel lining EC play a pivotal role in initiating chronic graft rejection. Disruption of the integrity of the endothelial layer is of undoubted impor...

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Benefits of technology

[0015]The present invention is also directed to an implantable material for reducing an immune response to a syngeneic or non-syngeneic cell, tissue or organ. According to this aspect of the invention, the implantable material comprises a biocompatible matrix and, anchored thereto and/or embedded therein, endothelial cells, endothelial-like cells, or analogs thereof. According to this aspect of the invention, an effective amount of the implantable material reduces the recipient's immune response to the syngeneic or non-syngeneic cell, tissue or organ. According to one embodiment of this aspect of the present invention, the cell, tissue or organ is that of the recipient suffering from an autoimmune disease.

[0016]The invention is also directed to a variation of the above-described implantable material which is useful for reducing an immune response to a non-syngeneic cell, tissue or organ, wherein said implantable material comprises cells, tissue, or organ or a segment thereof anchored to and/or embedded within the biocompatible matrix. An effective amount of this implantable material reduces the recipient's immune response to a non-syngeneic cell, tissue or org

Problems solved by technology

However, host immune responses present a formidable barrier to transplantation across species.

While such agents permit some degree of transplant acceptance, success is limited and perhaps of more significance, a patient's immune system is thoroughly compromised as a resu

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