Antigenic modulation of cells

• US 5,908,624 A
• Filed: 06/27/1996
• Issued: 06/01/1999
• 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: Eaton, John W., Scott, Mark D.
• Primary Examiner(s): Caputa, Anthony C.
• Assistant Examiner(s): HAYES, ROBERT CLINTON
• Application Number:
  US08/671,452
• Time in Patent Office: 1,069 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 2035/124 the cells being hematopoietic, bone marrow derived or blood cells
• CPC Class Codes: A61K 35/18 Erythrocytes haemoglobin A61K38/42
• 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 5/0641 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; a linker molecule covalently attached to the cell surface; and a non-immunogenic compound (e.g., polyethylene glycol or derivative thereof) covalently attached to the linker molecule. 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 by virtue of the long chain length of the non-immunogenic compound. 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-immunogenic cellular composition comprising:

a cell having a cell surface and antigenic determinants of said cell surface;

a linker molecule covalently attached to said cell surface; and

a non-immunogenic compound covalently attached to said linker molecule and blocking recognition of said antigenic determinants on said cell surface, wherein said cell is a vascular endothelial cell.

2. The cellular composition of claim 1 wherein said non-immunogenic compound is polyethylene glycol.

3. The cellular composition of claim 1 wherein said non-immunogenic compound is methoxypolyethylene glycol.

4. The cellular composition of claim 1 wherein said non-immunogenic compound is polyethylene oxide.

5. The cellular composition of claim 1 wherein said non-immunogenic compound is dextran.

6. The cellular composition of claim 1 wherein said non-immunogenic compound is ficoll.

7. The cellular composition of claim 1 wherein said non-immunogenic compound is arabinogalactan.

8. The cellular composition of claim 1 wherein said linker molecule is cyanuric chloride.

9. The cellular composition of claim 1 wherein said linker molecule is imidazolyl formate.

10. The cellular composition of claim 1 wherein said linker molecule is succinimidyl succinate.

11. The cellular composition of claim 1 wherein said linker molecule is succinimidyl glutarate.

12. The cellular composition of claim 1 wherein said linker molecule is N-hydroxysuccinimide.

13. The cellular composition of claim 1 wherein said linker molecule is 4-nitrophenol.

14. The cellular composition of claim 1 wherein said linker molecule is 2,4,5-trichlorophenol.

15. The cellular composition of claim 1 wherein said linker molecule is covalently attached to said antigenic determinant on said cell surface.

16. The cellular composition of claim 1 wherein said cell is a vascular endothelial cell.

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

covalently attaching a non-immunogenic compound to a linker molecule, and said non-immunogenic compound blocking recognition of antigenic determinants on a cell surface; and

covalently attaching said linker molecule to a cell surface, so as to produce a non-immunogenic cell, wherein said non-immunogenic cell is a vascular endothelial cell.

18. The method of claim 17 wherein said linker molecule is covalently attached to said antigenic determinant on said cell surface.

19. The method of claim 17 wherein said non-immunogenic cell is a vascular endothelial cell.

20. The method of claim 19 further comprising transplanting a subject with said non-immunogenic cell.