# US 12,109,236 B2 · Manipulating ARID5B expression in immune cells to promote metabolism, survival, and function

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- Number: US 12,109,236 B2
- Document ID: US12109236B2
- Status: Granted
- Kind: B2
- Application number: 17/055,525
- Filed: 2019-05-08
- Published: 2021-05-27
- Granted: 2024-10-08
- Earliest claimed: 2018-05-14
- Assignees: Regents of the University of Minnesota
- Applicants: Regents of the University of Minnesota
- Inventors: Jeffrey Steven Miller; Frank Martin Cichocki
- Web page: https://patentgrep.com/patent/US12109236B2

## CPC

- C07K 14/7051: {T-cell receptor (TcR)-CD3 complex}
- 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)
- A61K 40/11: T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer [LAK] cells
- A61K 40/15: Natural-killer [NK] cells; Natural-killer T [NKT] cells
- A61K 40/46: Viral antigens
- C07K 14/47: from mammals
- C07K 14/4702: {Regulators; Modulating activity}
- C12N 5/0646: {Natural killers cells [NK], NKT cells}
- C07K 2319/03: containing a transmembrane segment
- C12N 2510/00: Genetically modified cells
- Y02A 50/30: Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## Abstract

Provided herein are methods of manipulating ARID5B expression in immune cells such NK cells, T cells, and T cell and NK cell progenitors to enhance their persistence and function in vivo. Also provided herein are modified immune cells and compositions comprising such modified cells for anti-cancer, anti-viral, and other immunotherapies. In some embodiments, immune cells are genetically modified to increase ARID5B expression and, thus, improve persistence, increase in vivo anti-tumor efficacy, and increase viability and functionality of the modified cells after freezing and thawing.

## Claims

### Claim 1

An isolated population of Natural Killer (NK) cells comprising a recombinant nucleic acid encoding an AT-rich interaction domain 5B (ARID5B) polypeptide operably linked to a heterologous promoter, wherein the NK cells exhibit increased expression of said ARID5B polypeptide relative to a wild-type NK cell.

### Claim 2 (depends on 1)

The population of claim 1, wherein the NK cells are primary NK cells or NK-92 cells.

### Claim 3 (depends on 1)

The population of claim 1, wherein the NK cells are CD3−, TCR−, CD56+, and NKp46+.

### Claim 4 (depends on 1)

The population of claim 1, wherein the NK cells are differentiated in vitro from stem cells, hematopoietic stem or progenitor cells, or progenitor cells.

### Claim 5 (depends on 1)

The population of claim 1, wherein the NK cells are differentiated in vitro from a CD34+ hemogenic endothelium cell, a multipotent progenitor cell, or a NK progenitor cell.

### Claim 6 (depends on 1)

The population of claim 1, wherein the NK cells are differentiated in vitro from induced pluripotent stem cells.

### Claim 7 (depends on 1)

The population of claim 1, wherein the NK cells comprise a recombinant nucleic acid encoding a T-cell receptor (TCR) or a chimeric antigen receptor (CAR).

### Claim 8 (depends on 1)

The population of claim 1, wherein the NK cells are produced in vitro or ex vivo from immune cells isolated from or comprised in peripheral blood.

### Claim 9 (depends on 1)

The population of claim 1, wherein the NK cells are human.

### Claim 10 (depends on 1)

A cell composition comprising the population of NK cells of claim 1 and a carrier or excipient.

### Claim 11 (depends on 1)

A pharmaceutical composition comprising the population of NK cells of claim 1 and a pharmaceutically acceptable carrier or excipient.

### Claim 12 (depends on 1)

A therapeutic composition for treating a tumor in a subject comprising the population of NK cells of claim 1, wherein the NK cells are suspended in a pharmaceutically acceptable medium suitable for injection.