Method of Treating a Malignancy in a Subject Via Direct Picornaviral-Mediated Oncolysis

Abstract

There are provided methods for treatment of abnormal cells such as cancer cells in a mammal. The methods involve treating the mammal with virus selected from echoviruses and modified forms and combination thereof, which recognize α 2 β 1 for infectivity of the cells. There are also provided methods for screening viruses for use in a method of the invention as well as pharmaceutical compositions for use in the methods.

1 . A method for treatment of abnormal cells in a mammal, the method comprising treating the mammal with an effective amount of virus selected from echo-viruses, and modified forms and combinations thereof, which recognise α 2 β 1  for infectivity of the cells such that at least some of the cells are killed by the virus. 
     
     
         2 . A method according to  claim 1  comprising subjecting the mammal to a number of treatments with the virus, and the virus in each of the treatments is the same or different. 
     
     
         3 . (canceled) 
     
     
         4 . A method according to  claim 1  wherein the virus is selected from the group consisting of EV1, EV7, EV8 and EV22. 
     
     
         5 . A method according to  claim 1  wherein the virus is a modified echovirus. 
     
     
         6 . (canceled) 
     
     
         7 . A method according to  claim 5  wherein the modified echovirus is a modified form of an echovirus selected from a group consisting of EV1, EV7, EV8 and EV22. 
     
     
         8 . A method according to  claim 1  wherein the virus is administered to the mammal in combination with a further virus which infects the abnormal cells. 
     
     
         9 . (canceled) 
     
     
         10 . A method according to  claim 8  wherein the further virus is a Coxsackievirus or modified form thereof. 
     
     
         11 . (canceled) 
     
     
         12 . A method according to  claim 1 , wherein the abnormal cells are cancer cells. 
     
     
         13 . A method according to  claim 12  wherein the cancer cells are cells of a cancer selected from a group consisting of ovarian cancer, melanoma, prostate cancer, breast cancer, pancreatic cancer, colon cancer and colorectal cancer, or have spread from ovarian cancer, melanoma, prostate cancer, breast cancer, pancreatic cancer, colon cancer or colorectal cancer. 
     
     
         14 . (canceled) 
     
     
         15 . A method according to  claim 1 , wherein the virus is administered topically, systemically or intratumorally to the mammal. 
     
     
         16 - 35 . (canceled) 
     
     
         36 . A method for inducing an immune response in a mammal against abnormal cells expressing α 2 β 1 , the method comprising infecting abnormal cells in the mammal with virus selected from echoviruses, and modified forms and combinations thereof, whereby lysis of at least some of cells is caused. 
     
     
         37 . A method according to  claim 36  wherein the virus comprises an echovirus serotype of modified form thereof. 
     
     
         38 . A method according to  claim 37  wherein the virus is selected from the group consisting of EV1, EV7, EV8 and EV22. 
     
     
         39 . A method according to  claim 37  wherein time virus is a modified echovirus. 
     
     
         40 . (canceled) 
     
     
         41 . (canceled) 
     
     
         42 . A method according to  claim 36 , wherein the abnormal cells have up-regulated expression of α 2 β 1 . 
     
     
         43 . A method according to  claim 36 , wherein the virus is administered to the mammal in combination with a further virus which infects the abnormal cells. 
     
     
         44 - 48 . (canceled) 
     
     
         49 . A method according to  claim 36 , wherein the virus is administered topically, systemically or intratumorally to the mammal. 
     
     
         50 . A pharmaceutical composition for treating abnormal cells in a mammal, comprising an inoculant for generating virus to treat the cells such that at least some of the cells are killed by the virus together with a pharmaceutically acceptable carrier, wherein the virus is selected from echoviruses, and modified forms and combinations thereof, which recognise α 2 β 1  for infectivity of the cells. 
     
     
         51 . (canceled) 
     
     
         52 . A pharmaceutical composition according to  claim 50  wherein the virus is selected from the group consisting of EV1, EV7, EV8 and EV22. 
     
     
         53 . (canceled) 
     
     
         54 . (canceled) 
     
     
         55 . A pharmaceutical composition according to  claim 50 , wherein the modified echovirus is a modified form of an echovirus selected from a group consisting of EV1, EV7, EV8 and EV22. 
     
     
         56 - 63 . (canceled)