Method of treating a malignancy in a subject and a pharmaceutical composition for use in same

Abstract

There is a disclosed a method of killing abnormal cells such as malignant cells including melanoma cells, using a virus recognising at least one of a cell adhesion molecule and a complement regulatory protein. The virus may be a member of the Picornaviridae family. Coxsackie A-group viruses have been found to be particularly suitable. The cell adhesion molecule is desirably a member of the immunoglobulin (Ig) superfamily. Typically, the complement regulatory protein will be DAF.

1 . A method of treating abnormal cells in a mammal comprising administering to the mammal an effective amount of a virus capable of infecting the abnormal cells whereby death of the cells is caused and which recognises at least one of a cell adhesion molecule of the immunoglobulin (Ig) superfamily and a complement regulatory protein for infectivity of the abnormal cells. 
     
     
         2 . A method according to  claim 1  wherein the cell adhesion molecule is ICAM-1. 
     
     
         3 . A method according to  claim 1  wherein the virus recognises both the cell adhesion molecule and the complement regulatory protein for infectivity of the abnormal cells. 
     
     
         4 . A method according to  claim 1  wherein the virus recognises the complement regulatory protein for infectivity of the abnormal cells, optionally wherein the complement regulatory protein is DAF. 
     
     
         5 . (canceled) 
     
     
         6 . A method according to  claim 1  wherein expression of the cell adhesion molecule is upregulated on the abnormal cells relative to normal said cells expressing their normal phenotype or is upregulated on the abnormal cells relative to cells of surrounding tissue in which the abnormal cells are found. 
     
     
         7 . (canceled) 
     
     
         8 . A method according to  claim 1  wherein the virus is selected from the group consisting of an animal RNA virus, such as an Enterovirus, a Coxsackievirus, such as CAV 13, CAV 15, CAV 18 and CAV 21, a recombinant virus. 
     
     
         9 - 12 . (canceled) 
     
     
         13 . A method according to  claim 1  wherein the abnormal cells are cells of a malignancy selected from the group consisting of a malignancy of the skin, prostate cancer, stomach cancer, breast cancer and colon cancer. 
     
     
         14 . A method according to  claim 1  wherein the virus is administered intravenously, intratumorally, intraperitoneally, intramuscularly, or by topical application. 
     
     
         15 . (canceled) 
     
     
         16 . A method according to  claim 1  wherein the virus is administered to the patient in a dosage greater than about 1×10 2  plaque forming units per ml of innoculant 
     
     
         17 - 32 . (canceled) 
     
     
         33 . A method of screening abnormal cells for determining whether the cells are susceptible to viral induced cell death, comprising the steps of:
 (a) providing the abnormal cells;   (b) adding to the cells an effective amount of a virus which recognises at least one of a cell adhesion molecule of the immunoglobulin (Ig) superfamily and a complement regulatory protein for infectivity of the abnormal cells; optionally (i) wherein the cell adhesion molecule is ICAM-1, (ii) wherein the complement regulatory protein is DAF;   (c) incubating the abnormal cells in the presence of the virus for a period of time; and   (d) determining whether the virus has infected and caused death of at least some of the abnormal cells.   
     
     
         34 - 37 . (canceled) 
     
     
         38 . A method according to  claim 33  wherein (i) expression of the cell adhesion molecule is upregulated on the abnormal cells relative to normal said cells expressing their normal phenotype and or (ii) expression of the cell adhesion molecule is upregulated on the abnormal cells relative to cells of surrounding tissue in which the abnormal cells are found. 
     
     
         39 . (canceled) 
     
     
         40 . A method according to  claim 33  wherein the virus is selected from the group consisting of an animal RNA virus, a member of the Picornaviridae family, an Enterovirus, a Coxsackievirus. 
     
     
         41 - 43 . (canceled) 
     
     
         44 . A method according to  claim 33  wherein the abnormal cells are cells of a malignancy selected from the group consisting of a malignancy of the skin, prostate cancer, stomach cancer, breast cancer and colon cancer. 
     
     
         45 - 54 . (canceled) 
     
     
         55 . A method of screening a virus for ability to infect and cause death of abnormal cells, comprising the steps of:
 (a) selecting a virus which recognises at least one of a cell adhesion molecule of the (Ig) superfamily and a complement regulatory protein for infectivity of the abnormal cells; optionally (i) wherein the cell adhesion molecule is ICAM-1, or (ii) wherein the complement regulatory protein is DAF;   (b) incubating the selected said virus with a sample of the abnormal cells for a period of time; and   (c) determining whether the selected said virus causes death of at least some of the abnormal cells; optionally wherein the abnormal cells are cells of a malignancy selected from the group consisting of a malignancy of the skin, prostate cancer, stomach cancer, breast cancer and colon cancer.   
     
     
         56 . A method according to  claim 55  further comprising comparing the ability of the virus to infect and cause the death of the abnormal cells with that of a different said virus subjected to steps (b) and (c) utilising another sample of the cells. 
     
     
         57 - 61 . (canceled) 
     
     
         62 . A method according to  claim 55  wherein expression of the cell adhesion molecule is upregulated on the abnormal cells relative to normal said cells expressing their normal phenotype. 
     
     
         63 - 77 . (canceled) 
     
     
         78 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier together with a virus capable of infecting abnormal cells whereby death of the cells is caused and which recognises at least one of a cell adhesion molecule of the immunoglobulin (Ig) superfamily and a complement regulatory protein for infectivity of the abnormal cells; optionally (i) wherein the cell adhesion molecule is ICAM-1, or (ii) wherein the complement regulatory protein is DAF. 
     
     
         79 - 84 . (canceled) 
     
     
         85 . A pharmaceutical composition according to  claim 78  wherein the virus is selected from the group consisting of an animal RNA virus, such as an Enterovirus, a Coxsackievirus, such as CAV 13, CAV 15, CAV 18 and CAV 21, a recombinant virus. 
     
     
         86 - 88 . (canceled) 
     
     
         89 . A pharmaceutical composition according to  claim 78  wherein the abnormal cells are malignant cells of a malignancy selected from the group consisting of a malignancy of the skin, prostrate cancer, stomach cancer, breast cancer and colon cancer. 
     
     
         90 - 129 . (canceled)