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EP-4740017-A1 - AN IN VITRO METHOD FOR DETECTING CANCER

EP4740017A1EP 4740017 A1EP4740017 A1EP 4740017A1EP-4740017-A1

Abstract

The present invention relates to an in vitro method for detecting cancer in a subject, for predicting the clinical outcome of a subject suffering from cancer, or for monitoring the treatment of a subject suffering from cancer, based on the tumoral carbohydrate Ca10 (Ca10) levels measured in a biofluid sample isolated from the subject.

Inventors

  • SUBIZA GARRIDO-LESTACHE, José Luis
  • Angelina Querencias, Alba
  • Tudela Garcia, José Ignacio
  • Moltó Delgado, Luis Manuel
  • Fernández Arquero, Miguel
  • Viñuela Martín, Marcos
  • CAÑADA VICINAY, Francisco Javier
  • Kalograiaki, Ioanna
  • PALOMARES GRACIA, OSCAR
  • Martín de la Cruz, Leticia

Assignees

  • Inmunotek, S.L.
  • Fundación Investigación del Hospital Clínico San Carlos Madrid

Dates

Publication Date
20260513
Application Date
20241120

Claims (10)

  1. 1. An in vitro method for detecting cancer in a subject, comprising: (a) quantifying the tumoral carbohydrate Ca10 (Ca10) levels in a biofluid sample isolated from the subject; and (b) comparing the Ca10 levels obtained in step (a) with a control level, Wherein if the Ca10 levels in the subject are increased with respect to the control levels, then the subject suffers from cancer.
  2. 2. An in vitro method for predicting the clinical outcome of a subject suffering from cancer, or for monitoring the treatment of a subject suffering from cancer, comprising (a) quantifying the tumoral carbohydrate Ca10 (Ca10) levels in a biological sample isolated from the subject; and (b) comparing the Ca10 levels obtained in step (a) with a control level, Wherein if the Ca10 levels in the subject are increased with respect to the control level, then the clinical outcome of the subject is negative and either the subject is going to suffer from metastasis or the tumoral mass is going to increase; or the treatment is not effective.
  3. 3. The method according to claim 1 or 2, wherein the cancer is a carcinoma or an adenocarcinoma.
  4. 4. The method according to any one of claims 1 to 3, wherein the cancer is prostate cancer, cervix cancer, breast cancer, pancreatic cancer, lung cancer, gastric cancer, endometrial cancer, skin cancer, thyroid cancer, bladder cancer, ovarian cancer, lever cancer, esophageal cancer, or colorectal cancer.
  5. 5. The method according to any one of claims 1 to 4, wherein the biofluid sample is blood, serum, plasma, pleural liquid, bronchioalveolar liquid, peritoneal liquid, urine, or sputum.
  6. 6. Use of a kit for detecting cancer in vitro, or for predicting in vitro the clinical outcome of a subject suffering from cancer, or for monitoring in vitro the treatment of a subject suffering from cancer, wherein the kit comprises elements for quantifying the Ca10 levels in a biological sample of a subject.
  7. 7. Use of a kit for detecting cancer in vitro, or for predicting in vitro the clinical outcome of a subject suffering from cancer, or for monitoring in vitro the treatment of a subject suffering from cancer, according to claim 6, wherein the cancer is a carcinoma or an adenocarcinoma.
  8. 8. Use of a kit for detecting cancer in vitro, or for predicting in vitro the clinical outcome of a subject suffering from cancer, or for monitoring in vitro the treatment of a subject suffering from cancer, according to claim 6 or 7, wherein the cancer is prostate cancer, cervix cancer, breast cancer, pancreatic cancer, lung cancer, gastric cancer, endometrial cancer, skin cancer, thyroid cancer, bladder cancer, ovarian cancer, lever cancer, esophageal cancer, or colorectal cancer.
  9. 9. Use of a kit for detecting cancer in vitro, or for predicting in vitro the clinical outcome of a subject suffering from cancer, or for monitoring in vitro the treatment of a subject suffering from cancer, according to any one of claims 6 to 8, wherein the biological sample is blood, serum or plasma pleural liquid, bronchioalveolar liquid, peritoneal liquid, urine, or sputum.
  10. 10. Use of a kit for detecting cancer in vitro, or for predicting in vitro the clinical outcome of a subject suffering from cancer, or for monitoring in vitro the treatment of a subject suffering from cancer, according to any one of claims 6 to 9, wherein the elements are antibodies, or a fragment thereof, peptides or aptamers, all of them with affinity for Ca10.

Description

AN IN VITRO METHOD FOR DETECTING CANCER The invention refers to an in vitro method for cancer detection based on the tumor- associated carbohydrate Ca10 (Ca10) levels in a biological fluid sample. Thus, the present invention relates to the technical field of cancer, specifically, to tumor serum markers thereof. BACKGROUND ART Malignant transformation is accompanied by changes in tumor cell surface carbohydrates, including aberrant or incomplete glycosylation of heavily glycosylated structures. These structures can be released from tumor cells and detected in the biological fluids of cancer patients, making them useful as tumor markers. In addition, their presence may be associated with cancer prognosis by influencing metastasis and tumor progression. The carbohydrate Ca10 is a highly glycosylated structure present on the cell surface of murine Ehrlich tumor (ET) cells. Ca10 was defined by its reactivity with the monoclonal antibody A10, obtained from hybridomas derived from mice immunized with ET cells. Ca10 is spontaneously released from ET cells and can be detected in the serum of solid ET-bearing mice. Therefore, there is the necessity in the state to the art to increase the insights on tumor escape mechanisms in order to develop new tools in the detection of cancer. DESCRIPTION OF THE INVENTION By studying the serum levels of murine Ca10 (mCa10) in mice bearing solid murine Ehrlich carcinoma, a strong correlation between mCa10 levels and tumor mass was established. mCa10 is a proteoglycan with a heparan sulfate glycosaminoglycan structure, sensitive to certain heparinases (heparinase 3). The heparan sulfate structure found in mCa10 is peculiar for its extremely low sulfatation degree. It would be related to the non-sulfated precursor of this glycosaminoglycan, heparosan, normally absent on the cell surface of mammalian cells. The analysis of the main carbohydrate component in mCa10, either by nuclear magnetic resonance (NMR) or by chromatography of the released fragments after complete hydrolysis with heparinases only shows a significant proportion (20-40%) of non-acetylated glucosamine residues. It does not show sulfation of either glucosamine or glucuronic acid residues, contrary to what could be expected for normally processed heparan sulfate glycosaminoglycan present in healthy tissues. This discrepancy suggests a typical processing or modification in the mCa10 heparan sulfate glycosaminoglycan. Surprisingly, circulating levels of a human homologue (Ca10H) of the murine tumor glycosaminoglycan mCa10 are detected in the serum of cancer patients with tumors originating from different tissues. Apart from their common reactivity with A10, the structural relationship between mCa10 and Ca10H is based on their high sensitivity to heparinase 3, which is highly specific for glycosaminoglycans of heparan sulfate. Circulating Ca10H levels are found to be elevated in serum of cancer patients, on a cut-off established with sera from control subjects. Of note, in patients with prostate cancer, it has been possible to establish a correlation between serum Ca10H levels and bone metastases. Since Ca10H levels in serum vary among cancer patients with different or the same histological tumor type, Ca10H could represent a new “tumor marker” with additional clinical usefulness as a prognostic factor. Uses of Ca10 as a tumor marker. In view of the foregoing, the present invention discloses Ca10H as a “tumor marker”, this is, a substance that is found in high levels in biofluid sample of some people with cancer in comparison with non-suffering cancer people. Tumor markers are produced either by the cancer cells themselves or by the body in response to the presence of cancer or certain benign (noncancerous) conditions. Based on the above, a first aspect the present invention relates to an in vitro method for detecting cancer in a subject, hereinafter “detection method of the invention”, comprising: (a) quantifying the tumoral carbohydrate Ca10 levels in a biofluid sample isolated from the subject; and (b) comparing the Ca10 levels obtained in step (a) with a control level, Wherein if the Ca10 levels in the subject are increased with respect to the control levels, then the subject suffers from cancer. As used herein, the term “cancer detection” refers to the identification of a tumoral tissue by examination or parameters or biomarkers in a subject. In the context of the present invention, the parameter required for detecting cancer is the Ca10H levels in a biofluid sample of the subject. As use herein, the term “cancer” refers to the disease resulting from the uncontrolled proliferation of cells giving rise to a malignant tumour or to a malignant tumoral tissue. A tumour is considered malignant when the tumour cells can grow rapidly, show anaplasia and/or are able to infiltrate the tissue, invade adjacent tissues or even spread to other parts of the body, a process known as metastasis. Thus, in one particular embodiment