Antigenic modulation of cells

• US 8,007,784 B1
• Filed: 06/01/1999
• Issued: 08/30/2011
• Est. Priority Date: 06/27/1996
• Status: Expired due to Term

• Current Assignee: Albany Medical College (Albany Medical Center)
• Original Assignee: Albany Medical College (Albany Medical Center)
• Inventors: Scott, Mark D., Eaton, John W.
• Primary Examiner(s): HAYES, ROBERT CLINTON
• Application Number:
  US09/323,765
• Time in Patent Office: 4,473 Days
• Field of Search: 424/93.7, 424/93.1, 424/184.1, 435/325, 435/382, 435/177, 435/178, 435/181, 435/1.1
• US Class Current: 424/93.7
• CPC Class Codes: A61K 2039/515 Animal cells
• CPC Class Codes: A61K 35/17 Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes when activated by a specific antigen A61K39/00
• CPC Class Codes: A61K 35/30 Nerves; Brain; Eyes; Corneal cells; Cerebrospinal fluid; Neuronal stem cells; Neuronal precursor cells; Glial cells; Oligodendrocytes; Schwann cells; Astroglia; Astrocytes; Choroid plexus; Spinal cord tissue
• CPC Class Codes: A61K 35/36 Skin; Hair; Nails; Sebaceous glands; Cerumen; Epidermis; Epithelial cells; Keratinocytes; Langerhans cells; Ectodermal cells islets of Langerhans A61K35/39
• CPC Class Codes: A61K 35/39 Pancreas; Islets of Langerhans Langerhans cells of epidermis A61K35/36
• CPC Class Codes: A61K 35/407 Liver; Hepatocytes
• 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 47/60 the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
• CPC Class Codes: A61K 47/6901 Conjugates being cells, cell fragments, viruses, ghosts, red blood cells or viral vectors
• CPC Class Codes: C12N 5/0006 Modification of the membrane of cells, e.g. cell decoration
• CPC Class Codes: C12N 5/0641 Erythrocytes
• CPC Class Codes: C12N 5/0644 Platelets; Megakaryocytes

Abstract

The present invention is directed to a non-immunogenic cellular composition comprising: a cell having a cell surface and antigenic determinants on the cell surface; an optional linker molecule covalently attached to the cell surface; and a hydrophilic, biocompatible, non-immunogenicity providing compound or polymer (e.g., polyethylene glycol or a derivative thereof) covalently attached to the linker molecule or directly to the cell. In one embodiment, the linker molecule is covalently attached directly to the antigenic determinant on the cell surface. In an alternate embodiment, the linker molecule may be covalently attached to a non-antigenic site on the cell surface, but will camouflage the antigenic determinant on the cell surface. Various uses of the resulting non-immunogenic cell are also provided, including a method of decreasing phagocytosis of a cell, a method of decreasing an adverse reaction to a transfusion, a method of decreasing rejection of a transplanted cell, tissue or organ, and a method of decreasing antibody-induced aggregation of cells.

Claims

1. A non-aggregating, non-immunogenic nuclear cellular composition in which at least 25% by number of nuclear cells in said composition remain viable for 96 hours consisting of:

a) a mammalian nuclear cell having a cell surface and antigenic determinants on said surface;

b) a sufficient amount of hydrophilic, biocompatible, non-immunogenicity providing compound or polymer covalently attached to said surface so that recognition of said antigenic determinants on said surface is blocked by said covalently bonded hydrophilic, biocompatible, non-immunogenicity providing compound or polymer.

2. The cellular composition of claim 1 wherein said cell is a lymphocyte and the covalently bonded hydrophilic, biocompatible, non-immunogenicity providing compound or polymer is covalently bonded to the nuclear cell through a unit derived from reaction of a cyanuric chloride linking group on the covalently bonded hydrophilic, biocompatible, non-immunogenicity providing compound or polymer to the cell surface.

3. The cellular composition of claim 1 wherein linking moieties covalently attach the hydrophilic, biocompatible, non-immunogenicity providing compound or polymer to said surface, said linking moieties are covalently attached to said antigenic determinants on said cell surface and said nucleated cell is a vascular endothelial cell.

4. The cellular composition of claim 1 wherein linking moieties covalently attach the hydrophilic, biocompatible, non-immunogenicity providing compound or polymer to said surface, said linking moieties are covalently attached to said antigenic determinants on said cell surface and said nucleated cell is a hepatic cell.

5. The cellular composition of claim 1 wherein linking moieties covalently attach the hydrophilic, biocompatible, non-immunogenicity providing compound or polymer to said surface, said linking moieties are covalently attached to said antigenic determinants on said cell surface and said nucleated cell is a neuronal cell.

6. The cellular composition of claim 5 wherein said cell is part of a tissue or organ and the covalently bonded hydrophilic, biocompatible, non-immunogenicity providing compound or polymer is covalently bonded to the nuclear cell through a unit derived from reaction of a cyanuric chloride linking group on the covalently bonded hydrophilic, biocompatible, non-immunogenicity providing compound or polymer to the cell surface.

7. The cellular composition of claim 1 wherein linking moieties covalently attach the hydrophilic, biocompatible, non-immunogenicity providing compound or polymer to said surface, said linking moieties are covalently attached to said antigenic determinants on said cell surface and said nucleated cell is a pancreatic cell.

8. The cellular composition of claim 1 wherein linking moieties covalently attach the hydrophilic, biocompatible, non-immunogenicity providing compound or polymer to said surface, said linking moieties are covalently attached to said antigenic determinants on said cell surface and said nucleated cell is an epithelial cell.

9. A non-aggregating, non-immunogenic anuclear cellular composition consisting of:

a) a mammalian anuclear cell having a cell surface and antigenic determinants on said surface;

a sufficient amount of hydrophilic, biocompatible, non-immunogenicity providing compound or polymer covalently attached to said surface so that recognition of said antigenic determinants on said surface is blocked by said covalently bonded hydrophilic, biocompatible, non-immunogenicity providing compound or polymer wherein linking moieties are covalently bonded to said antigenic determinants on said cell surface.

10. A non-aggregating, non-immunogenic anuclear cellular composition consisting of:

a) a mammalian anuclear cell having a cell surface and antigenic determinants on said surface;

a sufficient amount of hydrophilic, biocompatible, non-immunogenicity providing compound or polymer covalently attached to said surface so that recognition of said antigenic determinants on said surface is blocked by said covalently bonded hydrophilic, biocompatible, non-immunogenicity providing compound or polymer wherein said cell is an anuclear cell and the covalently bonded hydrophilic, biocompatible, non-immunogenicity providing compound or polymer is covalently bonded to the nuclear cell through a unit derived from reaction of a cyanuric chloride linking group on the covalently bonded hydrophilic, biocompatible, non-immunogenicity providing compound or polymer to the cell surface.

11. A non-aggregating, non-immunogenic anuclear cellular composition consisting of:

b) a mammalian anuclear cell having a cell surface and antigenic determinants on said surface;

a sufficient amount of hydrophilic, biocompatible, non-immunogenicity providing compound or polymer covalently attached to said surface so that recognition of said antigenic determinants on said surface is blocked by said covalently bonded hydrophilic, biocompatible, non-immunogenicity providing compound or polymer wherein said cell is a platelet and the covalently bonded hydrophilic, biocompatible, non-immunogenicity providing compound or polymer is covalently bonded to the nuclear cell through a unit derived from reaction of a cyanuric chloride linking group on the covalently bonded hydrophilic, biocompatible, non-immunogenicity providing compound or polymer to the cell surface.

12. A method of producing a non-immunogenic mammalian cell, said method comprising:

covalently attaching an amount of hydrophilic, biocompatible, non-immunogenicity providing compound or polymer to the cell surface, directly or by means of a linking moiety, so that said hydrophilic, biocompatible, nonimmunogenicity providing compound or polymer blocks recognition of antigenic determinants on the cell surface and yields a non-immunogenic cell wherein linking moieties covalently attach the hydrophilic, biocompatible, non-immunogenicity providing compound or polymer to said surface, said linking moiety is covalently bonded to said antigenic determinants on said cell surface.