# US 2019/0170756 A1 · Tirc7 based diagnostic and therapy of solid cancer

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- Number: US 2019/0170756 A1
- Document ID: US20190170756A1
- Status: Published application
- Kind: A1
- Application number: 16/324,393
- Filed: 2017-08-10
- Published: 2019-06-06
- Earliest claimed: 2016-08-10
- Assignees: Nekonal S.A.R.L.
- Applicants: Nekonal S.a.r.l.
- Inventors: Nalan UTKU
- Web page: https://patentgrep.com/patent/US20190170756A1

## CPC

- G01N 33/5759: {involving compounds localised on the membrane of tumour or cancer cells}
- A61P 35/00: Antineoplastic agents
- C07K 16/28: against receptors, cell surface antigens or cell surface determinants
- C07K 16/3061: {Blood cells}
- C12Q 1/00: Measuring or testing processes involving enzymes, nucleic acids or microorganisms (measuring or testing apparatus with condition measuring or sensing means, e.g. colony counters, C12M1/34); Compositions therefor; Processes of preparing such compositions
- C12Q 1/6886: for cancer (immunoassay for cancer G01N33/575)
- G01N 33/57595: {involving intracellular compounds}
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- C12Q 2600/106: Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
- C12Q 2600/112: Disease subtyping, staging or classification
- 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)
- 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)
- 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
- 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)

## Abstract

The present invention pertains to a combined diagnostic and therapeutic approach for cancer patients comprising the analysis of the biomarker T cell immune response cDNA 7 (TIRC7) and, depending on its expression in tumor cells, tumor infiltrating lymphocytes (TIL) and T regulatory cells (Treg) in a patient, the use of TIRC7 as a target for therapy. In particular, the invention provides methods for stratifying patients with cancer into two groups one of which will benefit from a TIRC7 modulatory treatment and one of which are non-responders to such a therapy. Furthermore, the invention provides compounds for the treatment of patients that are identified as responders according to the invention. Thus, the present disclosure offers a true theranostic approach for patients with various cancers via tackling immune escape of the cancer, in particular solid tumors, based on TIRC7.

## Claims

### Claim 1

An ex vivo method for stratifying a solid cancer patient into one of patient groups (i) or (ii), wherein patient group (i) is a solid cancer patient group that will benefit from a T cell immune response cDNA 7 (TIRC7)-modulatory treatment, and patient group (ii) is a solid cancer patient group that will not benefit from a TIRC7 modulatory treatment, the method comprising the ex vivo method steps of
(a) Providing a sample of tumor tissue of the solid cancer of the patient, wherein the tumor tissue comprises a tumor cell and/or a tumor infiltrating immune cell,
(b) Determining the expression of TIRC7 in or on the tumor cell and/or infiltrating immune cell, and
(C) Depending on the resultant of step (b), stratifying the patient into group (i) in the event the tumor cell in the tumor tissue and/or the immune cell in the tumor tissue expresses TIRC7 compared to a control cell, or stratifying the patient into group (ii) in the event the tumor cell in the tumor tissue and/or the immune cell in the tumor tissue does not express TIRC7 compared to a control cell.

### Claim 2

An ex vivo method for diagnosing a cancer patient to have a solid cancer disease which will respond to a TIRC7 modulatory treatment, the method comprising the ex vivo method steps of
(a) Providing a sample comprising a tumor tissue from said tumor in the cancer patient,
(b) Determining the expression of TIRC7 in a tumor cell in the tumor tissue or in an immune cell, such as a TIL, in the tumor tissue,
(c) Depending on the resultant of step (b), diagnosing the patient to have a solid cancer disease which will respond to a TIRC7 modulatory treatment in the event the tumor cell in the tumor tissue and/or the immune cell in the tumor tissue expresses TIRC7 compared to a control cell.

### Claim 3 (depends on 1, 2)

The method according to claim 1 or 2, wherein step (b) comprises determining the expression of TIRC7 and at least one additional immune cell factor such as FoxP3.

### Claim 4 (depends on 1, 2, 3)

The method according to any of claims 1 to 3, wherein TIRC7 modulatory treatment is an TIRC7 inhibitory treatment and wherein said TIRC7 modulator is a TIRC7 inhibitor.

### Claim 5 (depends on 1, 2, 3, 4)

The method according to any of claims 1 to 4, which is performed completely ex vivo, preferably in vitro.

### Claim 6 (depends on 1, 2, 3, 4, 5)

The method according to any of claims 1 to 5, wherein the TIRC7 modulatory treatment is a treatment comprising the administration of a TIRC7 modulator, such as an antibody binding to, and modulating, TIRC7, preferably wherein the antibody is metiliximab, or antibody derivatives of this molecule.

### Claim 7 (depends on 1, 2, 3, 4, 5, 6)

The method according to any of claims 1 to 6, wherein in step (b) the expression of TIRC7 in or on the cancer tumor cell and/or immune cell is determined on the protein level, for example by using an anti-TIRC7 antibody, or at the mRNA level, for example by a PCR-based detection method or hybridization technique.

### Claim 8 (depends on 1, 2, 3, 4, 5, 6, 7, 8)

The method according to any of claims 1 to 8, wherein said control cell is a cell not expressing TIRC7 protein (negative control).

### Claim 9 (depends on 1, 2, 3, 4, 5, 6, 7, 8)

The method according to any of claims 1 to 8, wherein the cancer patient is a relapsed or refractory cancer patient in which a previous therapy with a compound selected from the group consisting of an anti-CD20 antibody such as Rituximab, fludarabine and chlorodeoxiadenosine, has failed.

### Claim 10

A modulator of T cell immune response cDNA 7 (TIRC7) for use in the treatment of lymphoma solid cancer in a patient.

### Claim 11 (depends on 10)

The modulator of TIRC7 for use according to claim 10, wherein the solid cancer is a TIRC7 expressing solid cancer, and/or is a solid cancer characterized by the presence of tumor infiltrating lymphocytes in the tumor tissue.

### Claim 12 (depends on 10, 11)

The modulator of TIRC7 for use according to any of claims 10 to 11, wherein the treatment comprises a preceding stratification of the patient suffering from the solid cancer disease.

### Claim 13 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 12)

The modulator of TIRC7 for use according to claim 12, wherein the stratification is a stratification of the patient into one of patient groups (i) or (ii), wherein patient group (i) is a solid cancer patient group that will benefit from a T cell immune response cDNA 7 (TIRC7)-modulatory treatment, and patient group (ii) is solid cancer patient group that will not benefit from a TIRC7 modulatory treatment, according to method of any of claims 1 to 9.

### Claim 14 (depends on 10, 11, 12, 13)

The modulator of TIRC7 for use according to any of claims 10 to 13, wherein the patient is a relapsed or refractory solid cancer patient in which a previous therapy with a compound selected from the group consisting of anti-CD20 antibody such as Rituximab, fludarabine and chlorodeoxiadenosine, has failed.

### Claim 15 (depends on 10, 11, 12, 13, 14)

The modulator of TIRC7 for use according to any of claims 10 to 14, wherein the solid cancer is a cancer stemming from any solid organ tissue.

### Claim 16

A method for treating a patient suffering from solid cancer, the method comprising the steps of
(a) Determining the expression of TIRC7 in or on a tumor cell and/or immune cell comprised in a tumor tissue sample from the patient compared to a negative control,
(b) If the resultant of step (a) is that TIRC7 is expressed in or on the tumor cell and/or immune cell, administering to the patient a therapeutically effective dose of a TIRC7 modulator.

### Claim 17 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 16)

The method according to claim 16, wherein step (a) comprises a method according to any of claims 1 to 9.

### Claim 18 (depends on 16, 17)

The method according to claim 16 or 17, wherein the modulator of TIRC7 is an antibody binding to, and inhibiting, the extracellular domain of TIRC7, preferably wherein the antibody, or antibody derivatives of these molecules, such as chimerized, humanized, or otherwise optimized antibody molecules.

### Claim 19 (depends on 16, 17, 18)

The method according to any of claims 16 to 18, wherein the patient is a relapsed or refractory solid cancer patient in which a previous therapy with a compound selected from the group consisting of anti-CD20 antibody such as anti-PD1. PD1L, CTLA4 or other targeted therapies, has failed.

### Claim 20 (depends on 16, 17, 18, 19)

The method according to any of claims 16 to 19, wherein the therapeutically effective dose of a TIRC7 modulator induces an increased caspase 3 dependent apoptosis in tumor cells in said patient.