Universal Immune Receptor Expressed by T Cells for the Targeting of Diverse and Multiple Antigens

Patent metadata

Field	Value
Publication number	US-2019330300-A1
Application number	US-201916298310-A
Country	US
Kind code	A1
Filing date	Mar 11, 2019
Priority date	Sep 22, 2011
Publication date	Oct 31, 2019
Grant date	—

Abstract

The invention provides compositions and methods for adoptive T cell therapy in treating a variety of disorders including cancer, infections, and autoimmune disorders. In one embodiment, the invention provides a universal immune receptor (UnivIR) that comprises an extracellular label binding domain, a transmembrane domain, and a cytoplasmic domain or otherwise an intracellular domain.

First claim

1 .- 20 . (canceled)

21 . A method for stimulating a UnivIR-mediated immune response in a mammal, the method comprising administering to a mammal an effective amount of a cell genetically modified to express a universal immune receptor (UnivIR), wherein the UnivIR comprises an extracellular label binding domain, a transmembrane domain, a T cell receptor signaling domain, wherein the label binding domain binds to a labeled antigen.

22 . The method of claim 21 , wherein distinct antigens are targeted sequentially or simultaneously.

23 . The method of claim 21 , wherein the label binding domain comprises a biotin binding domain and wherein the biotin binding domain binds to a biotinylated antigen.

24 . The method of claim 23 , wherein the biotin binding domain comprises avidin, or a biotin binding fragment thereof.

25 . The method of claim 21 , wherein the label binding domain binds to a labeled antigen selected from the group consisting of a tumor antigen, a self-antigen, a viral antigen, and any combination thereof.

26 . The method of claim 21 , wherein the UnivIR further comprises an intracellular domain of a costimulatory molecule.

27 . The method of claim 26 , wherein the intracellular domain of a costimulatory molecule selected from the group consisting of CD27, CD28, CD2, 4-1BB, OX40, CD30, CD40, PD-1, ICOS, lymphocyte function-associated antigen-1 (LFA-1), CD7, LIGHT, NKG2C, B7-H3, a ligand that specifically binds with CD83, and any combination thereof.

28 . The method of claim 21 , wherein the label binding domain binds to a label selected from the group consisting of myc-tag, FLAG-tag, His-tag, HA-tag, fluorescein isothiocyanate (FITC), dinitrophenol, peridinin chlorophyll protein complex, green fluorescent protein, biotin, phycoerythrin (PE), histidine, streptavidin, avidin, horse radish peroxidase, palmitoylation, nitrosylation, alkalanine phosphatase, glucose oxidase, Glutathione S-transferase (GST), and maltose binding protein.

29 . The method of claim 21 , wherein the label binding domain binds to a label, wherein the label is selected from the group consisting of a peptide, oligonucleotide, small molecule, and ligand.

30 . The method of claim 21 , wherein the cell is an autologous cell.

31 . The method of claim 30 , wherein the cell is selected from the group consisting of a T cell, a Natural Killer (NK) cell, a cytotoxic T lymphocyte (CTL), and a regulatory T cell.

32 . The method of claim 21 , wherein the method further comprises administering an antigen binding composition to the mammal, wherein the antigen binding composition comprises a label.

Assignees

• Univ Pennsylvania

Inventors

• Scholler Nathalie
• Urbanska Katarzyna
• Powell Daniel J

Classifications

• C07K2319/03

  containing a transmembrane segment · CPC title

• C07K14/7051 Primary

  T-cell receptor (TcR)-CD3 complex · CPC title

• C07K14/465

  from birds · CPC title

• C07K14/70521

  CD28, CD152 · CPC title

• C07K14/70517

  CD8 · CPC title