# US 11,026,972 B2 · Methods for generating macrophages with enhanced cancer phagocytosis

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- Number: US 11,026,972 B2
- Document ID: US11026972B2
- Status: Granted
- Kind: B2
- Application number: 16/156,146
- Filed: 2018-10-10
- Published: 2019-05-09
- Granted: 2021-06-08
- Earliest claimed: 2016-04-10
- Assignees: Georgia State University Research Foundation, Inc.
- Applicants: Georgia State University Research Foundation, Inc.
- Inventors: Yuan Liu; Zhen Bian; Ke Zen
- Web page: https://patentgrep.com/patent/US11026972B2

## CPC

- A61K 47/6813: {the drug being a peptidic cytokine, e.g. an interleukin or interferon}
- A61K 31/7088: Compounds having three or more nucleosides or nucleotides
- A61K 31/739: Lipopolysaccharides
- A61K 38/19: Cytokines; Lymphokines; Interferons
- A61K 38/191: {Tumor necrosis factors [TNF], e.g. lymphotoxin [LT], i.e. TNF-beta}
- A61K 38/2006: {IL-1}
- A61K 38/204: {IL-6}
- A61K 38/217: {IFN-gamma}
- A61K 39/395: Antibodies (agglutinins A61K38/36 {; as drug carriers A61K47/50}); Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K 40/17: Monocytes; Macrophages
- A61K 40/22: Immunosuppressive or immunotolerising
- A61K 40/24: Antigen-presenting cells [APC]
- A61K 40/416: {Antigens related to auto-immune diseases; Preparations to induce self-tolerance}
- A61K 40/42: Cancer antigens
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 35/00: Antineoplastic agents
- C07K 16/244: {Interleukins [IL]}
- C07K 16/2896: {against molecules with a "CD"-designation, not provided for elsewhere}
- C12N 5/0645: {Macrophages, e.g. Kuepfer cells in the liver; Monocytes}
- C12N 15/1138: {against receptors or cell surface proteins}
- A61K 2039/505: {comprising antibodies}
- A61K 2239/38: characterised by the dose, timing or administration schedule
- A61K 2239/50: Colon
- A61K 2239/57: Skin; melanoma
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

The present invention relates to compositions and methods variously useful in treating cancer, inhibiting graft rejection, and treating autoimmune disease. The compositions and methods include those in which macrophages are conditioned to down regulate or upregulate the expression or activity of SIRPα or its interaction with CD47.

## Claims

### Claim 1

A method of generating macrophages with enhanced cancer phagocytosis, the method comprising:
(a) providing a biological sample from a subject, wherein the biological sample comprises macrophages;
(b) exposing the sample to an effective amount of a first composition comprising at least 100 units/ml IFNγ to suppress the expression or activity of signal regulatory protein α (SIRPα); and
(c) exposing the sample from step (b) to an effective amount of a second composition that activates Protein kinase C (PKC)-Spleen tyrosine kinase (Syk) pathway, thereby generating macrophages with enhanced cancer phagocytosis.

### Claim 2 (depends on 1)

The method of claim 1, wherein the biological sample further comprises cancer cells.

### Claim 3 (depends on 1)

The method of claim 1, wherein the biological sample further comprises dendritic cells.

### Claim 4 (depends on 1)

The method of claim 1, wherein the biological sample has been enriched for myeloid cells.

### Claim 5 (depends on 1)

The method of claim 1, wherein the first composition further comprises a Toll-like receptor (TLR) ligand.

### Claim 6 (depends on 5)

The method of claim 5, wherein the TLR ligand comprises a CpG oligonucleotide or a polyinosinic:polycytidylic acid (poly I:C).

### Claim 7 (depends on 5)

The method of claim 5, wherein the TLR ligand comprises GARDIQUIMOD or IMIQUIMOD.

### Claim 8 (depends on 1)

The method of claim 1, wherein the first composition further comprises, IL-6.

### Claim 9 (depends on 1)

The method of claim 1, wherein the first composition comprises a Toll-like receptor (TLR) ligand, IFNγ, and IL-6.

### Claim 10 (depends on 1)

The method of claim 1, wherein the second composition comprises phorbol 12-myristate 13-acetate (PMA).

### Claim 11 (depends on 1)

The method of claim 1, further comprising administering the macrophages with enhanced cancer phagocytosis to a subject.