Use of PDL1 expressing cells to convert T cells into regulatory T cells

• US 9,644,179 B2
• Filed: 11/20/2012
• Issued: 05/09/2017
• Est. Priority Date: 11/23/2011
• Status: Active Grant

• Current Assignee: Government Of The United States Of America, Represented By The Secretary, Department Of Health And Human Services, Trustees Of The University Of Pennsylvania (University of Pennsylvania)
• Original Assignee: United States Department Of Health And Human Services, Trustees Of The University Of Pennsylvania (University of Pennsylvania)
• Inventors: Riley, James L., Fowler, Daniel H., Amarnath, Shoba
• Primary Examiner(s): OUSPENSKI, ILIA I
• Application Number:
  US14/359,764
• Publication Number:
  US 20140341933A1
• Time in Patent Office: 1,631 Days
• Field of Search: None
• CPC Class Codes: A61K 2239/31 characterized by the route of administration
• CPC Class Codes: A61K 2239/38 characterised by the dose, timing or administration schedule
• 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 39/4611 T-cells, e.g. tumor infiltrating lymphocytes [TIL], lymphokine-activated killer cells [LAK] or regulatory T cells [Treg]
• CPC Class Codes: A61K 39/4621 immunosuppressive or immunotolerising
• CPC Class Codes: A61K 39/46434 Antigens related to induction of tolerance to non-self
• CPC Class Codes: A61K 39/464412 CD19 or B4
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: C12N 2501/998 Proteins not provided for elsewhere
• CPC Class Codes: C12N 2502/99 genetically modified cells
• CPC Class Codes: C12N 2506/11 from blood or immune system cells
• CPC Class Codes: C12N 2506/115 from monocytes, from macrophages
• CPC Class Codes: C12N 5/0637 Immunosuppressive T lymphocytes, e.g. regulatory T cells or Treg

Abstract

The present invention provides methods and compositions for converting a T cell into a cell that exhibits at least one regulatory T cell phenotype. The converted T cell is generated by contacting a T cell with a cell that is modified to comprise an agent capable of activating PD1 signaling in a T cell. The converted T cell is useful for preventing, suppressing, blocking or inhibiting an immune response. For example the converted T cell is useful for preventing rejection of a transplanted tissue in a human or other animal host, or protecting against graft versus host disease. The converted T cell can also be used to treat autoimmune diseases.

Claims

1. A method of converting a pathogenic T cell into a cell that exhibits a regulatory T cell phenotype, the method comprising contacting the pathogenic T cell with a K562 cell modified to express an agent selected from the group consisting of PDL1, PDL2, and an anti-PD1 antibody, thereby converting said pathogenic T cell into a cell that exhibits a regulatory T cell phenotype.

2. The method of claim 1, wherein said pathogenic T cell is a non-regulatory T cell selected from the group consisting of a CD4⁺ cell, a CD4⁺CD25⁻

cell, and a CD4⁺CD25⁻

45RA⁺ cell.

3. The method of claim 1, wherein said pathogenic T cell is selected from the group consisting of a Th1 cell, a Th2 cell, a Th17 cell, and any combination thereof.

4. The method of claim 1, wherein said converted regulatory T cell exhibits a phenotype selected from the group consisting of expression of Foxp3, suppression of effector T cell activation, and a combination thereof.

5. The method of claim 1, wherein said modified K562 cell is irradiated.

6. The method of claim 1, wherein said pathogenic T cell induces graft vs host disease (GVHD).