Engineered antigen presenting cells and methods for their use

• US 5,962,320 A
• Filed: 07/03/1997
• Issued: 10/05/1999
• Est. Priority Date: 04/20/1993
• Status: Expired due to Fees

• Current Assignee: Leland Stanford Junior University (Stanford University)
• Original Assignee: Leland Stanford Junior University (Stanford University)
• Inventors: Robinson, William S.
• Primary Examiner(s): RAILEY, JOHNNY F
• Application Number:
  US08/888,360
• Time in Patent Office: 824 Days
• Field of Search: 435/325, 435/366, 424/93.21
• US Class Current: 435/366
• CPC Class Codes: A61K 2039/5154 Antigen presenting cells [APCs], e.g. dendritic cells or macrophages
• CPC Class Codes: A61K 2039/5156 expressing foreign proteins
• CPC Class Codes: A61K 2039/55522 Cytokines; Lymphokines; Interferons
• CPC Class Codes: A61K 39/00 Medicinal preparations containing antigens or antibodies materials for immunoassay G01N33/53
• CPC Class Codes: A61K 39/39 characterised by the immunostimulating additives, e.g. chemical adjuvants
• CPC Class Codes: C07K 14/005 from viruses
• CPC Class Codes: C07K 14/70532 B7 molecules, e.g. CD80, CD86
• CPC Class Codes: C12N 2730/10122 New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
• CPC Class Codes: C12N 2740/12043 viral genome or elements thereof as genetic vector

Abstract

Autologous, heterologous or xenogeneic primary cells or cell lines are genetically modified ex vivo to render the cells capable of processing and presenting selected antigens to cells of the immune system of a subject, and to express different HLA molecules for matching to the HLA specificity of the subject. The cells are also modified to express immunoregulatory molecules for directing the immune response of the subject. The cells and cell lines are used in methods to treat infectious diseases or cancer, or to prevent infectious disease by inoculation into a host to activate T cells and induce an antigen-specific immune response, and in assays of the cytolytic activity of a subject'"'"'s T cells. The cells can also be used to suppress an unwanted immune response of a subject to a selected antigen where the cells lack expression of a costimulation molecule needed for T cell activation.

Claims

1. A cell of heterologous or xenogeneic origin that is not a professional antigen presenting cell, wherein said cell is engineered to express at least one ABC transporter protein and at least one costimulation molecule to function as an antigen presenting cell.

2. The cell of claim 1, wherein said protein is TAP 1 and/or TAP 2 protein.

3. A cell of heterologous or xenogeneic origin that is not a professional antigen presenting cell, wherein said cell is engineered to express at least one chemokine molecule and at least one costimulation molecule to function as an antigen presenting cell.

4. The cell of claim 3 wherein said chemokine molecule is selected from the group consisting of MCP-1 and RANTES.

5. A cell of heterologous or xenogeneic origin that is not a professional antigen presenting cell, wherein said cell is engineered to express at least one costimulation molecule to function as an antigen presenting cell, and wherein said costimulation molecule is selected from the group consisting of B7-1, B7-2, and B7-3.

8. The cell of claim 5, wherein said cell is further engineered to express HLA class I and class II molecules of different antigen specificity than endogenous HLA molecules of said cell.

9. The cell of claim 5, further engineered to express at least one selected antigen from the group consisting of cancer and infectious agent antigens.

6. A cell of heterologous or xenogeneic origin that is not a professional antigen presenting cell, wherein said cell is engineered to express an immunoregulatory molecule and at least one costimulation molecule to function as an antigen presenting cell.

7. The cell of claim 6, wherein said immunoregulatory molecule is a lymphokine selected from the group consisting of interferons, interleukins and tumor necrosis factors.

10. A cell that is not a professional antigen presenting cell, wherein said cell is engineered to present a selected antigen to T cells and to suppress T cell activation by the selected antigen, and wherein said cell expresses at least one ABC transporter protein and at least one chemokine.

11. A cell that is not a professional antigen presenting cell, wherein said cell is engineered to present a selected antigen to T cells and to suppress T cell activation by the selected antigen, and to express HLA class I and class II molecules of different antigen specificity than endogenous HLA molecules of said cell.

12. A cell of heterologous or xenogeneic origin that is not a professional antigen presenting cell, wherein said cell is engineered to express at least one costimulation molecule to function as an antigen presenting cell, and wherein said costimulation molecule is selected from the group consisting of 4.1 BB ligand, LFA-3, CD72, heat-stable and CD40 molecules.

13. A human cell line that is not a professional antigen presenting cell line and that originally expressed at least one endogenous human HLA molecule of an endogenous antigen specificity, said cell line engineered to express human HLA class I and class II molecules of different antigen specificity than the endogenous HLA molecules of said cell line.

14. The cell line of claim 13, engineered to express at least one costimulation molecule.

23. The cell line of claim 13, wherein said cell line is further engineered to express one or more selected antigens selected from the group consisting of an infectious agent or cancer antigen.

26. A plurality of engineered antigen presenting cell lines according to claim 13, each cell line engineered to express HLA class I and class II molecules of a single specificity and different cell lines expressing different HLA specificities corresponding to those of a range of human hosts.

15. A cell line that is not a professional antigen presenting cell line, wherein said cell line is engineered to express human HLA class I and class II molecules of different antigen specificity than the endogenous HLA molecules of said cell line and at least one costimulation molecule selected from the group consisting of B7-1, B7-2, and B7-3.

16. A cell line that lacks expression of costimulation molecules for T cell activation and that is not a professional antigen presenting cell line, wherein said cell line is engineered to express human HLA class I and class II molecules of different antigen specificity than the endoegnous HLA molecules of said cell line.

24. The cell line of claim 16, wherein said cell line is further engineered to express one or more selected antigens from the group consisting of autoantigens, transplantation antigens and allergens.

17. A cell line that is not a professional antigen presenting cell line, wherein said cell line is engineered to express human HLA class I and class II molecules of different antigen specificity than the endogenous HLA molecules of said cell line and at least one chemokine molecule.

18. The cell line of claim 17, wherein said chemokine molecule is selected from the group consisting of MCP-1 and RANTES.

19. A cell line that is not a professional antigen presenting cell line, wherein said cell line is engineered to express human HLA class I and class II molecules of different antigen specificity than the endogenous HLA molecules of said cell line and at least one ABC transporter protein.

20. The cell line of claim 19, wherein said ABC transporter protein is selected from the group consisting of TAP-1 and TAP-2 proteins.

21. A cell line that is not a professional antigen presenting cell line, wherein said cell line is engineered to express human HLA class I and class II molecules of different antigen specificity than the endogenous HLA molecules of said cell line;

and at least one immunoregulatory molecule.

22. The cell line of claim 21, wherein said immunoregulatory molecule is a lymphokine selected from the group consisting of interferons, interleukins and tumor necrosis factors.

25. A cell line that is not a professional antigen presenting cell line, wherein said cell line is engineered to express human HLA class I and class II molecules of different antigen specificity than the endogenous HLA molecules of said cell line and at least one costimulation molecule selected from the group consisting of 4.1 BB ligand, LFA-3, CD72, heat-stable and CD40 molecules.