Artificial antigen presenting cells and uses therefor

• US 7,754,482 B2
• Filed: 05/25/2005
• Issued: 07/13/2010
• Est. Priority Date: 05/27/2004
• Status: Active Grant

• Current Assignee: Trustees Of The University Of Pennsylvania (University of Pennsylvania)
• Original Assignee: Trustees Of The University Of Pennsylvania (University of Pennsylvania)
• Inventors: Suhoski, Megan M., June, Carl H., Riley, James L., Vonderheide, Robert H., Aqui, Nicole
• Primary Examiner(s): LI, QIAN JANICE
• Application Number:
  US11/137,807
• Publication Number:
  US 20060034810A1
• Time in Patent Office: 1,875 Days
• Field of Search: None
• US Class Current: 435/375
• CPC Class Codes: A61K 2035/124 the cells being hematopoietic, bone marrow derived or blood cells
• CPC Class Codes: A61K 2039/5154 Antigen presenting cells [APCs], e.g. dendritic cells or macrophages
• CPC Class Codes: A61K 2039/5158 Antigen-pulsed cells, e.g. T-cells
• CPC Class Codes: A61K 2039/55522 Cytokines; Lymphokines; Interferons
• CPC Class Codes: A61K 2039/55527 Interleukins
• CPC Class Codes: A61K 2039/55533 IL-2
• CPC Class Codes: A61K 39/12 Viral antigens
• CPC Class Codes: A61K 39/21 Retroviridae, e.g. equine infectious anemia virus
• CPC Class Codes: A61K 39/39 characterised by the immunostimulating additives, e.g. chemical adjuvants
• CPC Class Codes: A61K 47/642 the peptide or protein in the drug conjugate being a cytokine, e.g. IL2, chemokine, growth factors or interferons being the inactive part of the conjugate
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/10 Antimycotics
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: C12N 15/86 Viral vectors
• CPC Class Codes: C12N 2501/23 Interleukins [IL]
• CPC Class Codes: C12N 2501/2302 : Interleukin-2 (IL-2)
• CPC Class Codes: C12N 2501/51 : B7 molecules, e.g. CD80, CD86, CD28 (ligand), CD152 (ligand)
• CPC Class Codes: C12N 2501/515 : CD3, T-cell receptor complex
• CPC Class Codes: C12N 2501/599 : with CD designations not provided for elsewhere
• CPC Class Codes: C12N 2502/1114 : T cells
• CPC Class Codes: C12N 2502/99 : genetically modified cells
• CPC Class Codes: C12N 2510/00 : Genetically modified cells
• CPC Class Codes: C12N 2740/15043 : viral genome or elements thereof as genetic vector
• CPC Class Codes: C12N 5/0634 : Cells from the blood or the immune system
• CPC Class Codes: C12N 5/0635 : B lymphocytes
• CPC Class Codes: C12N 5/0636 : T lymphocytes
• CPC Class Codes: C12N 5/0637 : Immunosuppressive T lymphocytes, e.g. regulatory T cells or Treg
• CPC Class Codes: C12N 5/0639 : Dendritic cells, e.g. Langherhans cells in the epidermis
• CPC Class Codes: C12N 5/0694 : Cells of blood, e.g. leukemia cells, myeloma cells
• CPC Class Codes: G01N 33/505 : involving T-cells
• CPC Class Codes: G01N 33/56972 : White blood cells

Abstract

The invention relates to novel artificial antigen presenting cells (aAPCs). The aAPC comprises at least one stimulatory ligand and at least one co-stimulatory ligand where the ligands each specifically bind with a cognate molecule on a T cell of interest, thereby mediating expansion of the T cell. The aAPC of the invention can further comprise additional molecules useful for expanding a T cell of interest. The aAPC of the invention can be used as an “off the shelf” APC that can be readily designed to expand a T cell of interest. Also, the aAPC of the invention can be used identify the stimulatory, co-stimulatory, and any other factors that mediate growth and expansion of a T cell of interest. Thus, the present invention provides powerful tools for development of novel therapeutics where activation and expansion of a T cell can provide a benefit.

Claims

1. A method of expanding a population of CD25+CD4+ Treg cells, the method comprising:

contacting said population with;

(i) an artificial antigen presenting cell (aAPC) comprising a K562 cell, wherein said aAPC comprises CD64 on its surface loaded with an anti-CD3 antibody and CD86, wherein said CD64 is expressed from an exogenous expression vector; and

(ii) IL-2, wherein binding of said anti-CD3 antibody and said CD86 with said Treg cells induces proliferation of said Treg cells, thereby expanding said population of CD25+CD4+ Treg cells.

2. The method of claim 1, wherein said IL-2 is expressed from an exogenous expression vector, wherein said vector is in said aAPC.