# US 2024/0201192 A1 · Folr2+ macrophages and anti-tumor immunity

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- Number: US 2024/0201192 A1
- Document ID: US20240201192A1
- Status: Published application
- Kind: A1
- Application number: 18/286,252
- Filed: 2022-04-12
- Published: 2024-06-20
- Earliest claimed: 2021-04-12
- Assignees: Institut Curie; Institut National de la Sante et de la Recherche Medicale; Université Paris Cité; Centre National De La Recherche Scientifique
- Applicants: Institut Curie; Institut National de la Sante et de la Recherche Medicale; Universite Paris Cite; Centre National de la Recherche Scientifique
- Inventors: Rodrigo Nalio Ramos; Pierre Guermonprez; Eliane Piaggio; Julie Helft
- Web page: https://patentgrep.com/patent/US20240201192A1

## CPC

- G01N 33/5758: {involving compounds serving as markers for tumours, cancers or neoplasias, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides or metabolites}
- G01N 33/5759: {involving compounds localised on the membrane of tumour or cancer cells}
- C07K 16/28: against receptors, cell surface antigens or cell surface determinants
- C12Q 1/6886: for cancer (immunoassay for cancer G01N33/575)
- G01N 33/56972: {White blood cells}
- C12Q 2600/118: Prognosis of disease development
- C12Q 2600/158: Expression markers
- G01N 2800/52: Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
- 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)
- 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)
- C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES

## Abstract

The invention relates to tumor-associated FOLR2+ macrophages and gene signature thereof as a biomarker of favorable outcome and anti-tumor immunity useful for the prognosis and monitoring of cancer patients. The invention relates also to FOLR2+ macrophages as a therapeutic target for enhancing T cell immunity in the prevention and treatment of cancer and infectious diseases.

## Claims

### Claim at position 1

1-16. (canceled)

### Claim 17

A method of treating cancer in a patient, comprising:
determining the level of FOLR2+ macrophages in a patient tumor sample, wherein the level of tumor-associated FOLR2+ macrophages correlates positively with outcome of cancer disease or treatment in the patient;
deducing therefrom whether the outcome of cancer disease or treatment is likely to be favorable or unfavorable in the patient; and
administering an appropriate treatment to the patient depending on whether the outcome of cancer disease or treatment is likely to be favorable or not in the patient.

### Claim 18 (depends on 17)

The method according to claim 17, wherein an elevated level of FOLR2+ macrophages in the patient tumor sample as compared to a reference, indicates that the outcome of cancer disease or treatment is likely to be favorable in the patient.

### Claim 19 (depends on 17)

The method according to claim 17, wherein the favorable outcome of cancer disease comprises an increased survival time or rate, a decreased rate of relapse, an increased time to relapse, and/or a reduced tumor evolution or metastasis.

### Claim 20 (depends on 17)

The method according to claim 17, which comprises determining the density of FOLR2+ cells in the patient tumor sample.

### Claim 21 (depends on 20)

The method according to claim 20, comprising determining the density of FOLR2+ cells in the patient tumor sample by immunohistochemical technique using anti-FOLR2 antibody.

### Claim 22 (depends on 20)

The method according to claim 20, wherein the FOLR2+ cells are further TREM2− or TREM2low and/or CADM1−.

### Claim 23 (depends on 17)

The method according to claim 17, which comprises determining the level of expression of FOLR2 gene in the patient tumor sample.

### Claim 24 (depends on 23)

The method according to claim 23, which comprises determining the level of FOLR2 protein in the patient tumor sample.

### Claim 25 (depends on 17)

The method according to claim 17, which comprises determining the level of expression of a gene signature of tumor-associated FOLR2+ macrophages, which comprises or consists of the FOLR2, SEPP1 and SLC40A1 genes.

### Claim 26 (depends on 25)

The method according to claim 25, which comprises determining the level(s) of mRNA expressed by the FOLR2 gene or the FOLR2, SEPP1 and SLC40A1 genes by RNA-Seq.

### Claim 27 (depends on 17)

The method according to claim 17, further comprising a step of classification of the patient into favorable and unfavorable prognosis groups based on the level of tumor-associated FOLR2+ macrophages determined in the patient tumor sample.

### Claim 28 (depends on 27)

The method according to claim 27, comprising the administration of an immune checkpoint blockage agent or an endocrine therapy agent, if the patient is classified as having a favorable prognosis.

### Claim 29 (depends on 27)

The method according to claim 27, comprising the administration of a chemotherapy agent, or a combination of chemotherapy agent and immunotherapy agent or endocrine therapy agent if the patient is classified as having an unfavorable prognosis.

### Claim 30 (depends on 17)

The method according to claim 17, wherein the cancer is selected from the group consisting of: breast, kidney, lung, liver, skin, uterus, brain, thyroid and adrenal gland cancer.

### Claim 31

A targeted antigen delivery system comprising a FOLR2 binding ligand associated with an antigen of interest or a nucleic acid encoding the antigen in expressible form.

### Claim 32 (depends on 31)

The targeted antigen delivery system according to claim 31, wherein the antigen of interest is a vaccine antigen.

### Claim 33 (depends on 31)

The targeted antigen delivery system according to claim 31, wherein the FOLR2 binding ligand comprises an anti-FOLR2 antibody or fragment thereof comprising the antigen-binding site.

### Claim 34 (depends on 31)

The targeted antigen delivery system according to claim 31, wherein the FOLR2 binding ligand and antigen or nucleic acid thereof are associated in a conjugate, a fusion protein or a particle.

### Claim 35 (depends on 31)

A pharmaceutical composition, comprising the antigen delivery system according to claim 31, and at least one pharmaceutically acceptable vehicle, adjuvant and/or carrier.

### Claim 36

A gene signature of tumor-associated FOLR2+ macrophages comprising or consisting of the FOLR2, SEPP1 and SLC40A1 genes.
