Methods And Compositions For Treatment Of Interferon-Resistant Tumors

Abstract

The present invention provides a method for the treatment of interferon resistant bladder tumors through the use of a non-replicating agent which induces human cells to express interferon species. In particular it is noted that inducing interferon expression in the patient's body possesses properties not associated with recombinant produced, intravenously-administered interferon proteins. The present invention further provides compositions useful in the treatment of bladder cancer resistant to treatment with intravenous interferon polypeptide, by using a non-replicating agent which induces human cells to express interferon species, e.g., an antigenic, replication-deficient virus optionally carrying an interferon transgene.

1 . A composition of matter comprising: a non-interferon agent which induces interferon production in human cells which are exposed to it, said agent being replication-deficient, said agent formulated in normal saline as a non-emulsified suspension suitable for intravesical irrigation, said formulation providing said agent in an amount sufficient to induce interferon production in human bladder cells, said formulation further providing said agent in an amount effective to treat non-muscle invasive bladder cancer. 
     
     
         2 . The composition of matter of  claim 1 , wherein said replication-deficient agent comprises at least one component selected from the group consisting of replication-deficient virus and antigen. 
     
     
         3 . The composition of  claim 2  wherein said replication-deficient agent comprises antigen, said antigen comprising viral antigen of a replication-deficient virus. 
     
     
         4 . The composition of  claim 2  wherein said replication-deficient agent comprises an expressible interferon transgene. 
     
     
         5 . The composition of  claim 1 , further comprising Syn3. 
     
     
         6 . The composition of matter of  claim 1 , wherein said agent is provided in an amount sufficient to reduce the risk of non-muscle invasive bladder cancer resistant to, or recurrent after, intravesical treatment with live  Bacillus  Calmette-Guérin vaccine. 
     
     
         7 . The composition of claim wherein said replication-deficient agent comprises antigen. 
     
     
         8 . The composition of  claim 7  wherein said replication-deficient agent is provided in an amount sufficient to reduce the risk of non-muscle invasive bladder cancer resistant to, or recurrent after, intravesical treatment with live  Bacillus  Calmette-Guérin vaccine. 
     
     
         9 . The composition of  claim 5 , wherein said Syn3 and said agent are packaged together in a kit. 
     
     
         10 . A method of treating a human with cancer which is resistant to, or recurrent after, treatment with intravenous interferon polypeptide, comprising: transducing cells of said with a vector comprising the replication-deficient agent of  claim 4  comprising an expressible transgene coding for interferon polypeptide, in an amount sufficient for said transduced cells to express interferon in an amount sufficient to treat said cancer. 
     
     
         11 . The method of  claim 10 , wherein said vector comprises a recombinant virus. 
     
     
         12 . The method of  claim 11 , further comprising administering said virus with Syn3. 
     
     
         13 . A method of treating a human with bladder cancer which is resistant to or recurrent after intravesical treatment with live  Bacillus  Calmette-Guérin vaccine, comprising: intravesically administering the agent of  claim 1 . 
     
     
         14 . A method for delaying the progression of non-muscle invasive bladder cancer to muscular-invasive bladder cancer in a human patient, comprising: intravesically administering the agent of  claim 1 .