# US 2024/0201172 A1 · Use of odorant receptor for suppressing lactate-induced m2-type differentiation of tumor-associated macrophages and tumor growth

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 2024/0201172 A1
- Document ID: US20240201172A1
- Status: Published application
- Kind: A1
- Application number: 18/287,048
- Filed: 2022-02-18
- Published: 2024-06-20
- Earliest claimed: 2021-04-16
- Assignees: Kyungpook National University Industry-Academic Cooperation Foundation; Daegu Gyeongbuk Institute of Science and Technology
- Applicants: Kyungpook National University Industry-Academic Cooperation Foundation; Daegu Gyeongbuk Institute of Science and Technology
- Inventors: Byung-Heon LEE; Jaehyung KOO; Poongkavithai Vadevoo SRI MURUGAN
- Web page: https://patentgrep.com/patent/US20240201172A1

## CPC

- A61K 31/713: Double-stranded nucleic acids or oligonucleotides
- G01N 33/5055: {involving macrophages}
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 35/00: Antineoplastic agents
- C12N 15/1138: {against receptors or cell surface proteins}
- G01N 33/50: Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing (measuring or testing processes involving enzymes or microorganisms, compositions or test papers therefor; processes for forming such compositions, condition responsive control in microbiological or enzymological processes C12Q)
- G01N 33/5011: {for testing antineoplastic activity}
- A01K 2207/12: Animals modified by administration of exogenous cells
- A01K 2217/075: inducing loss of function, i.e. knock out
- A01K 2227/105: Murine
- A01K 2267/0331: Animal model for proliferative diseases
- C12N 2310/14: interfering nucleic acids [NA]
- G01N 2333/726: G protein coupled receptor, e.g. TSHR-thyrotropin-receptor, LH/hCG receptor, FSH
- G01N 2500/10: involving cells
- 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)
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- A01K: ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS

## Abstract

The present invention relates to use of an odorant receptor for suppressing the lactate-induced M2-type differentiation of tumor-associated macrophages and tumor growth. In particular, the inventors of the present invention assumed that lactate-activated OR Olfr78 would function as a macrophage lactate sensor, and confirmed whether Olfr78 on bone marrow-derived macrophages (BMDMs) detect tumor-derived lactate and lactate-induced M2 polarization. The inventors of the present invention attempted to identify factors detected by Olfr78 in tumor conditioned media (TCM), and discovered that lactate in TCM and acetic acid under some conditions are major factors involved in Olfr78-mediated generation of tumor-friendly M2-TAMs. Finally, it was found that Olfr78 deficiency inhibited tumor progression and metastasis and improved antitumor immunity in vivo (in vivo). According to the present invention, Olfr78-lactate interaction plays a major role in tumor progression, and thus, targeting of the Olfr78-lactate axis can be effectively used in targeted cancer therapy.

## Claims

### Claim 1

A method for preventing or treating cancer in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a pharmaceutical composition comprising an expression or activity inhibitor of odorant receptor Olfr78 or OR51E2 as an active ingredient.

### Claim 2 (depends on 1)

The method of claim 1, wherein the expression inhibitor of Olfr78 or OR51E2 is any one selected from the group consisting of antisense nucleotides, small interfering RNAs (siRNAs), and short hairpin RNAs (shRNAs) that complementarily bind to mRNA of Olfr78 or OR51E2 gene.

### Claim 3 (depends on 1)

The method of claim 1, wherein the activity inhibitor of Olfr78 or OR51E2 is any one selected from the group consisting of low molecular weight compounds, peptides, peptide mimetics, aptamers, antibodies, and natural products that specifically bind to Olfr78 or OR51E2 protein.

### Claim 4 (depends on 1)

The method of claim 1, wherein the composition inhibits lactate- or acetate-induced M2 polarization of macrophages.

### Claim 5 (depends on 1)

The method of claim 1, wherein the cancer is lung cancer or breast cancer.

### Claim 6

(canceled)

### Claim 7

A method of screening an anticancer drug, the method comprising:
(1) contacting test substances with isolated macrophages;
(2) measuring a degree of binding of odorant receptor Olfr78 or OR51E2 and Gpr132 in the macrophages contacted with the test substances; and
(3) selecting a test substance with a reduced degree of the binding of Olfr78 or OR51E2 and Gpr132 compared to a control sample.

### Claim 8 (depends on 7)

The method of claim 7, wherein the test substance inhibits lactate- or acetate-induced M2 polarization of macrophages.

### Claim 9 (depends on 7)

The method of claim 7, wherein the anticancer drug is an anticancer drug for lung cancer or breast cancer.

### Claim 10

A reagent composition for inducing lactate- or acetate-induced M2 polarization of macrophages in vitro, comprising odorant receptor Olfr78 or OR51E2 as an active ingredient.

### Claim 11

A method of inducing lactate- or acetate-induced M2 polarization of macrophages, comprising treating macrophages with odorant receptor Olfr78 or OR51E2 in vitro.