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...

AI Technical Summary

Benefits of technology

[0008]In one aspect, the present invention is a method of reducing an immune response or an inflammatory reaction. According to this method, a recipient is provided an implantable material comprising a biocompatible matrix and anchored and / or embedded endothelial cells, endothelial-like cells, or analogs thereof. The implantable material is provided to the recipient in an amount sufficient to reduce the immune response or inflammatory reaction in the recipient.

[0009]According to the invention, the providing step can occur prior to, coincident with, or subsequent to administration to the recipient of one or more doses of a cell, tissue or organ from a syngeneic or non-syngeneic donor. According to another embodiment, the providing step is prior to, coincident with, or subsequent to occurrence of an immune response or inflammatory reaction. According to another embodiment, the method reduces an immune response or an inflammatory response by modulating immunological memory.

[0011]Additionally, the present invention is directed to a method of reducing donor antigen immunogenicity. According to this method, an implantable material comprising a biocompatible matrix and anchored and / or embedded endothelial cells, endothelial-like cells, or analogs thereof are presented prior to, coincident with, or subsequent to introduction of the donor antigen to a recipient in an amount effective to reduce donor antigen immunogenicity. According to another embodiment, the donor and recipient are the same. According to a further embodiment, the recipient has an autoimmune disease. According to yet another embodiment, the donor antigen comprises a non-endothelial cell antigen.

[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.

[0017]In a further aspect, the present invention is a cell suitable for use with the implantable material of any one of inventions described herein. According to one embodiment, the endothelial-like cell or its analog is a non-endothelial cell. According to another embodiment, the analog is non-natural. According to a further embodiment, the cell, when anchored to and / or embedded within a biocompatible matrix, reduces a recipient's humoral or cellular immune response to a syngeneic or non-syngeneic donor cell, tissue or organ.

[0021]In a further aspect, the present invention is a method of reducing an immune response or an inflammatory reaction resulting from exposure to an exogenous immunogen. According to this method, a recipient is provided with an implantable material comprising a biocompatible matrix and anchored or embedded endothelial cells, endothelial-like cells, or analogs thereof. The implantable material is provided to the recipient in an amount sufficient to reduce the immune response or inflammatory reaction in the recipient resulting from exposure to the exogenous immunogen.

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 result of such agents.

Similarly, exogenous immunogens or stimuli have posed a clinical challenge.

These, too, can result in adverse immunological events or inflammatory reactions which necessitate treatment.

Successful management of such diseases has eluded clinicians to date.

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