Diagnosis and therapy of cancer involving cancer stem cells

Patent metadata

Field	Value
Publication number	US-2016159901-A1
Application number	US-201414904011-A
Country	US
Kind code	A1
Filing date	Jul 30, 2014
Priority date	Jul 31, 2013
Publication date	Jun 9, 2016
Grant date	—

Abstract

The present invention provides methods for diagnosis or treatment of cancer diseases involving cancer stem cells comprising targeting CLDN6. In particular, the present invention provides a method of determining cancer stem cells comprising detecting cells expressing CLDN6, Furthermore, the present invention provides a method of treating or preventing cancer comprising inhibiting and/or eliminating cancer stem cells by administering an antibody having the ability of binding to CLDN6 to a cancer patient.

First claim

1 . A method of determining cancer stem cells comprising detecting cells expressing CLDN6.

2 . The method of claim 1 wherein the presence of cells expressing CLDN6 indicates the presence of cancer stem cells and/or the amount of cells expressing CLDN6 correlates with the amount of cancer stem cells.

3 . The method of claim 1 or 2 wherein cells expressing CLDN6 are detected in a sample obtained from a cancer patient.

4 . The method of any one of claims 1 to 3 wherein the method comprises a quantitative and/or qualitative determination of cells expressing CLDN6.

5 . The method of any one of claims 1 to 4 which comprises comparing the amount of cells expressing CLDN6 to the amount of cells expressing CLDN6 in a reference sample or to a predetermined reference range.

6 . The method of claim 5 wherein the reference sample is a sample from a patient who has not been diagnosed with cancer.

7 . The method of claim 5 wherein the predetermined reference range is based on a population of patients who have not been diagnosed with cancer.

8 . The method of any one of claims 1 to 7 which comprises monitoring the amount of cancer stem cells in a cancer patient.

9 . The method of claim 8 , wherein monitoring the amount of cancer stem cells in a cancer patient comprises comparing the amount of cancer stem cells in a sample obtained from the cancer patient to the amount of cancer stem cells in a sample obtained earlier from the cancer patient.

10 . The method of claim 9 wherein the sample obtained from the cancer patient is a sample taken from the cancer patient during or following the administration of cancer therapy.

11 . A method of monitoring the efficacy of a cancer therapy in a cancer patient comprising:
(i) determining the amount of cancer stem cells in a sample obtained from the cancer patient during or following the administration of the cancer therapy; and (ii) comparing the amount of cancer stem cells in the sample obtained from the cancer patient to the amount of cancer stem cells in a sample obtained earlier from the cancer patient, wherein determining the amount of cancer stem cells in the sample obtained from the cancer patient and/or determining the amount of cancer stem cells in the sample obtained earlier from the cancer patient comprises determining the amount of cells expressing CLDN6.

12 . The method of any one of claims 9 to 11 wherein the sample obtained earlier from the cancer patient is a sample taken from the cancer patient prior to, during or following the administration of cancer therapy.

13 . The method of any one of claims 10 to 12 wherein a stabilization or a decrease in the amount of cancer stem cells indicates that the cancer therapy is effective.

14 . The method of any one of claims 10 to 12 wherein an increase in the amount of cancer stem cells indicates that the cancer therapy is ineffective.

15 . The method of any one of claims 10 to 14 wherein the cancer therapy is cancer therapy directed against cancer stem cells.

16 . The method of any one of claims 3 to 15 wherein the sample obtained from the cancer patient is a biological fluid or a tumor biopsy.

17 . The method of any one of claims 3 to 11 wherein the sample has been subjected to one or more pretreatment steps.

18 . The method of any one of claims 1 to 17 wherein the cells expressing CLDN6 are detected or their amount is determined by using an immunoassay.

19 . The method of claim 18 wherein the immunoassay is selected from the group consisting of western blots, immunohistochemistry, radioimmunoassays, ELISA (enzyme linked immunosorbent assay), “sandwich” immunoassays, immunoprecipitation assays, precipitation reactions, gel diffusion precipitation reactions, immunodiffusion assays, agglutination assays, complement-fixation assays, immunoradiometric assays, fluorescent immunoassays, immunofluorescence, protein A immunoassays, flow cytometry and FACS analysis.

20 . The method of any one of claims 1 to 19 wherein the cells expressing CLDN6 are detected or their amount is determined by using an antibody having the ability of binding to CLDN6.

21 . The method of any one of claims 1 to 20 wherein the cells expressing CLDN6 are cancer cells expressing CLDN6 and/or are cells which are present at a tumor site.

22 . A method of treating or preventing cancer comprising inhibiting and/or eliminating cancer stem cells by administering an antibody having the ability of binding to CLDN6 to a cancer patient.

23 . The method of claim 22 wherein the cancer stem cells express CLDN6.

24 . The method of claim 22 or 23 which further comprises administering chemotherapy and/or radiation therapy.

25 . The method of any one of claims 22 to 24 wherein inhibiting and/or eliminating cancer stem cells enhances the anti-cancer effect of chemotherapy and/or radiation therapy.

26 . The method of claim 25 wherein enhancement of the anti-cancer effect of chemotherapy and/or radiation therapy comprises an expansion of the lifespan of a cancer patient undergoing chemotherapy and/or radiation therapy.

27 . A method of treating or preventing cancer comprising administering (i) an antibody having the ability of binding to CLDN6 and (ii) chemotherapy to a cancer patient.

28 . The method of claim 27 wherein the cancer involves cancer stem cells expressing CLDN6.

29 . The method of claim 27 or 28 wherein administering an antibody having the ability of binding to CLDN6 results in inhibition or elimination of cancer stem cells expressing CLDN6.

30 . The method of any one of claims 27 to 29 wherein administering an antibody having the ability of binding to CLDN6 enhances the anti-cancer effect of chemotherapy.

31 . The method of claim 30 wherein enhancement of the anti-cancer effect of chemotherapy comprises an expansion of the lifespan of a cancer patient undergoing chemotherapy.

32 . The method of any one of claims 22 to 26 and 29 to 31 wherein elimination of cancer stem cells results in curing of cancer.

33 . The method of any one of claims 24 to 32 wherein the antibody having the ability of binding to CLDN6 and the chemotherapy are administered in synergistically effective amounts.

34 . The method of any one of claims 24 to 33 wherein the chemotherapy is administered at a dose which is below the maximum tolerated dose.

35 . The method of any one of claims 24 to 34 wherein the chemotherapy comprises administering an agent selected from the group consisting of taxanes, platinum compounds, nucleoside analogs, camptothecin analogs, anthracyclines, prodrugs thereof, salts thereof, and combinations thereof.

36 . The method of any one of claims 24 to 35 wherein the chemotherapy comprises administering an agent selected from the group consisting of paclitaxel, cisplatin, carboplatin, prodrugs thereof, salts thereof, and combinations thereof.

37 . The method of any one of claims 22 to 26 and 28 to 36 wherein the cancer stem cells are at a tumor site of the cancer patient.

38 . The method of any one of claims 22 to 37 wherein the cancer is resistant to chemotherapy, in particular if administered as

Assignees

• Ganymed Pharmaceuticals Ag
• Tron Translationale Onkologie An Der Universitätsmedizin Der Johannes Gutenberg
• Biontech Ag

Inventors

• Sahin Ugur
• Tureci Ozlem
• Walter Korden
• Wagner Meike
• Kreuzberg Maria
• Hacker Sabine
• Jacobs Stefan

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• G01N33/5759

  involving compounds localised on the membrane of tumour or cancer cells · CPC title

• G01N33/5758 Primary

  involving compounds serving as markers for tumours, cancers or neoplasias, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides or metabolites · CPC title

• A61N5/10

  X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy (A61N5/01 takes precedence) · CPC title