Materials and Methods for Treatment of Cancer

Abstract

Glypican 5 is shown for the first time to have a role in proliferation of cancer cells, including tumours which do not show chromosomal amplification at 13q31. The use of glypican 5 (GPC5) antagonists and binding agents for the treatment of cancer, particularly rhabdomyosarcoma and breast cancer, is disclosed.

1 - 41 . (canceled) 
     
     
         42 . A method of inhibiting proliferation of a target cell, comprising contacting the cell with a GPC5 antagonist or a GPC5 binding agent. 
     
     
         43 . A method according to  claim 42  wherein the target cell inappropriately expresses or overexpresses GPC5. 
     
     
         44 . A method according to  claim 42  wherein the cell inappropriately expresses or overexpresses WT1. 
     
     
         45 . A method according to  claim 42  wherein the cell is a cancer cell. 
     
     
         46 . A method according to  claim 45  wherein the cancer is selected from the group consisting of rhabdomyosarcoma, lymphoma, non-small cell lung cancer, bladder cancer, breast cancer, prostate cancer, a neuroglial tumour, squamous cell carcinoma of the head and neck, leukemia, leiomyosarcoma, liposarcoma, malignant fibrous histocytoma of bone or soft tissues, melanoma, mesothelioma, thyroid cancer, lung cancer, testicular cancer and ovarian cancer. 
     
     
         47 . A method according to  claim 42  wherein the cell does not carry a chromosomal amplicon at 13q31. 
     
     
         48 . A method according to  claim 42  wherein the binding agent binds to GPC5 protein. 
     
     
         49 . A method according to  claim 48  wherein the binding agent is an antibody or a peptide. 
     
     
         50 . A method according to  claim 48  further comprising contacting the cell with a therapeutic agent. 
     
     
         51 . A method according to  claim 50  wherein the therapeutic agent is associated with the binding agent. 
     
     
         52 . A method according to  claim 50  wherein the therapeutic agent is capable of binding to the binding agent. 
     
     
         53 . A method according to  claim 50  wherein the therapeutic agent comprises a moiety selected from the group consisting of a cytotoxic molecule, a precursor molecule capable of being converted into a cytotoxic molecule by enzyme action, a cell or molecule of the immune system, and a viral vector. 
     
     
         54 . A method according to  claim 42  wherein the binding agent binds to heparan sulphate chains associated with GPC5 protein. 
     
     
         55 . A method according to  claim 54  wherein the binding agent is an antibody or a peptide. 
     
     
         56 . A method according to  claim 42  wherein the GPC5 antagonist inhibits activity of GPC5 protein. 
     
     
         57 . A method according to  claim 56  wherein the GPC5 antagonist is an antibody or a peptide. 
     
     
         58 . A method according to  claim 56  further comprising contacting the cell with a therapeutic agent. 
     
     
         59 . A method according to  claim 58  wherein the GPC5 antagonist increases the sensitivity of the cell to the therapeutic agent. 
     
     
         60 . A method of determining the susceptibility of a cancer to treatment with a GPC5 antagonist or binding agent, comprising determining the presence, absence or level of expression of GPC5 and/or WT1 in a cell from said cancer. 
     
     
         61 . A method according to claim  19  further comprising the step of determining the presence, absence or degree of chromosomal amplification at 13q31 in a cell from said cancer. 
     
     
         62 . A method of determining the susceptibility of a cancer to treatment with a GPC5 antagonist or binding agent, comprising determining the presence, absence or degree of chromosomal amplification at 13q31. 
     
     
         63 . A method according to  claim 62  further comprising determining the presence, absence or level of expression of GPC5 and/or WT1 in a cell from said cancer. 
     
     
         64 . A method according to  claim 60  wherein the cancer is selected from the group consisting of rhabdomyosarcoma, lymphoma, non-small cell lung cancer, bladder cancer, breast cancer, prostate cancer, a neuroglial tumour, squamous cell carcinoma of the head and neck, leukemia, leiomyosarcoma, liposarcoma, malignant fibrous histocytoma of bone or soft tissues, melanoma, mesothelioma, thyroid cancer, lung cancer, testicular cancer and ovarian cancer. 
     
     
         65 . A method of screening for the presence of a cancer in a patient, the method comprising determining the presence, absence or level of circulating GPC5 in the patient. 
     
     
         66 . A method according to  claim 65  comprising determining the presence, absence or level of circulating GPC5 in a sample derived from the patient. 
     
     
         67 . A method according to  claim 66  wherein the sample is selected from the group consisting of blood, serum and plasma. 
     
     
         68 . A method according to  claim 66  wherein the method comprises contacting the sample with a GPC5 binding agent. 
     
     
         69 . A method according to  claim 65  wherein the cancer is selected from the group consisting of rhabdomyosarcoma, lymphoma, non-small cell lung cancer, bladder cancer, breast cancer, prostate cancer, a neuroglial tumour, squamous cell carcinoma of the head and neck, leukemia, leiomyosarcoma, liposarcoma, malignant fibrous histocytoma of bone or soft tissues, melanoma, mesothelioma, thyroid cancer, lung cancer, testicular cancer and ovarian cancer. 
     
     
         70 . A method of screening for an agent capable of inhibiting proliferation of a target cell, comprising the steps of:
 (i) contacting GPC5 protein with one or more candidate substances;   (ii) selecting one or more candidate substances based on their ability to bind GPC5 protein;   (iii) contacting said one or more selected substances with a target cell; and   (iv) determining the effect of said selected substance(s) on proliferation of said cell.   
     
     
         71 . A method according to  claim 70  wherein the cell inappropriately expresses or overexpresses GPC5. 
     
     
         72 . A method according to  claim 70  wherein the cell is a cancer cell. 
     
     
         73 . A method according to  claim 72  wherein the cancer is selected from the group consisting of rhabdomyosarcoma, lymphoma, non-small cell lung cancer, bladder cancer, breast cancer, prostate cancer, a neuroglial tumour, squamous cell carcinoma of the head and neck, leukemia, leiomyosarcoma, liposarcoma, malignant fibrous histocytoma of bone or soft tissues, melanoma, mesothelioma, thyroid cancer, lung cancer, testicular cancer and ovarian cancer. 
     
     
         74 . A method for determining a prognosis for a patient with breast cancer comprising assigning a prognosis to the patient based on the expression levels of GPC5 in a breast tumour from that patient. 
     
     
         75 . A method according to  claim 74  which comprises determining the presence, absence or degree of expression of GPC5 in vitro using a sample containing breast cancer cells from the patient. 
     
     
         76 . A method according to  claim 75  which comprises contacting the sample with a GPC5 binding agent. 
     
     
         77 . A method for monitoring the success of a treatment for a cancer previously found to express GPC5, comprising determining GPC5 expression in cells of the cancer. 
     
     
         78 . A method according to  claim 77  comprising contacting cells of the cancer with a GPC5 binding agent. 
     
     
         79 . A method according to  claim 78  which is performed in vitro using a sample containing cancer cells from the patient. 
     
     
         80 . A method according to  claim 77  comprising comparing the results obtained with results of an equivalent assay performed for the same patient before treatment and/or at an earlier stage of treatment. 
     
     
         81 . A method according to  claim 77  comprising determining the level of expression of GPC5 within cells of the cancer, or determining the number or density of cells expressing or overexpressing GPC5.