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

• US 9,040,092 B2
• Filed: 08/09/2012
• Issued: 05/26/2015
• Est. Priority Date: 04/21/2005
• Status: Expired due to Fees

• Current Assignee: Massachusetts Institute of Technology
• Original Assignee: Massachusetts Institute of Technology
• Inventors: Edelman, Elazer R., Nugent, Helen Marie, Methe, Heiko
• Primary Examiner(s): BELYAVSKYI, MICHAIL A
• Application Number:
  US13/570,320
• Publication Number:
  US 20130177600A1
• Time in Patent Office: 1,020 Days
• Field of Search: None
• US Class Current: 424/577
• CPC Class Codes: A61K 2035/122 for inducing tolerance or supression of immune responses
• CPC Class Codes: A61K 35/44 Vessels; Vascular smooth muscle cells; Endothelial cells; Endothelial progenitor cells
• CPC Class Codes: A61K 39/001 Preparations to induce tolerance to non-self, e.g. prior to transplantation
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/00 Medicinal preparations characterised by special physical form nuclear magnetic resonance contrast preparations or magnetic resonance imaging contrast preparations A61K49/18; preparations containing radioactive substances A61K51/12
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C12N 2533/54 Collagen; Gelatin
• CPC Class Codes: C12N 5/069 Vascular Endothelial cells

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.

Claims

1. A method of treating a recipient of a cell, tissue or organ from a donor, the method comprising the steps of:

administering to the recipient one or more doses of a cell, tissue or organ from a syngeneic or non-syngeneic donor; and

providing to the recipient an implantable material comprising

a biocompatible matrix; and

,

endothelial cells anchored or embedded in a 3D matrix,

wherein the providing step is prior to, coincident with, or subsequent to administration to said recipient of the one or more doses of a cell, tissue or organ from a syngeneic or non-syngeneic donor, and

wherein said implantable material is delivered locally at a non-luminal site to the recipient in an amount sufficient to systemically modulate the recipient'"'"'s humoral or cellular immune response to said donor cell, tissue or organ.

2. The method of claim 1, wherein said method modulates a recipient'"'"'s humoral or cellular immune response to administration of a non-syngeneic donor cell, tissue or organ.

3. The method of claim 1, wherein modulation of the recipient'"'"'s immune response results in reduced maturation of innate immune cells, wherein said innate immune cells are selected from the group consisting of NK cells, dendritic cells, monocytes, and macrophages.

4. The method of claim 3, wherein modulation of the recipient'"'"'s immune response results in reduced expression by dendritic cells of HLA-DR, IL 12, Toll-like receptor or CD83;

inhibits dendritic cell-induced lymphocyte proliferation;

or inhibits proliferation, activation or differentiation of dendritic cells.

5. The method of claim 1, wherein the cells embedded in the matrix are autologous, allogeneic, xenogeneic or genetically-modified variants or any one of the foregoing.

10. The method of claim 1, wherein the cells embedded in the matrix are vascular endothelial cells.

12. The method of claim 1, wherein the cells embedded in the matrix are selected from the group consisting of:

progenitor cells, stem cells, non-endothelial cells, and genetically-altered, -engineered or -modified cells.

6. A method of treating an individual exposed to an exogenous immunogen, the method comprising the steps of:

identifying an individual exposed to or likely exposed to an exogenous immunogen; and

administering to the individual exposed to the exogenous immunogen an implantable material comprising

a biocompatible matrix; and

,

endothelial cells anchored or embedded in a 3D matrix,

wherein the administering step is prior to, coincident with, or subsequent to the exogenous immunogen, and

wherein said implantable material is administered locally at a non-luminal site to said individual exposed to the exogenous immunogen in an amount sufficient to systemically reduce the exposed individual'"'"'s immune inflammatory reaction resulting from exposure to the exogenous immunogen.

7. The method of claim 6, wherein said exogenous immunogen is naturally occurring.

8. The method of claim 6, wherein said exogenous immunogen is selected from the group consisting of pharmaceutical agents, toxins, surgical implants, infectious agents and chemicals.

9. The method of claim 6, wherein the cells embedded in the matrix are autologous, allogeneic, xenogeneic or genetically-modified variants or any one of the foregoing.

11. The method of claim 6, wherein the cells embedded in the matrix are vascular endothelial cells.

13. The method of claim 6, wherein the cells embedded in the matrix are selected from the group consisting of:

progenitor cells, stem cells, non-endothelial cells, and genetically-altered, -engineered or -modified cells.