CDKN2a Companion Diagnostic for Bladder Cancer Interferon Therapy

Abstract

A method of treating a human with bladder cancer that is not responsive to treatment with bacillus Calmette-Guérin, comprising measuring the human's level of CDKN2A expression, and then instilling into the human an agent which induces interferon expression, e.g., interferon polypeptide or a gene therapy vector carrying an interferon transgene.

We claim: 
     
         1 . A method of treating non-muscle invasive bladder cancer in a human, comprising:
 a. identifying a human diagnosed with non-muscle invasive bladder cancer, and then   b. measuring the human's level of CDKN2A expression, and then   c. instilling into the lumen of the bladder of said human interferon.   
     
     
         2 . The method of  claim 1 , where the bladder cancer is high-grade. 
     
     
         3 . The method of  claim 1 , where the interferon is administered as a non-replicating vector. 
     
     
         4 . The method of  claim 3 , where said non-replicating vector comprises a replication-deficient viral vector carrying an interferon transgene. 
     
     
         5 . The method of  claim 4 , where said replication-deficient viral vector carrying an interferon transgene comprises nadofaragene firadenovec. 
     
     
         8 . The method of  claim 1 , where said measuring the human's level of CDKN2A expression entails taking a bladder tissue sample and measuring the level of CDKN2A expression in that tissue sample. 
     
     
         9 . The method of  claim 1 , where said measuring the human's level of CDKN2A expression entails taking a urine sample and measuring the level of CDKN2A expression in it. 
     
     
         10 . The method of  claim 9 , where said measuring the level of CDKN2A expression comprises analyzing the exosomes in said urine sample. 
     
     
         11 . The method of  claim 9 , wherein said measuring the level of CDKN2A expression comprises analyzing free DNA in said urine sample. 
     
     
         12 . The method of  claim 1 , further comprising the step of administering to said human a checkpoint inhibitor after said step of measuring the level of CDKN2A expression. 
     
     
         13 . The method of  claim 1 , wherein said step of measuring the human's level of CDKN2A expression comprises using fluorescent in situ hybridization using a probe able to hybridize with a portion of CDKN2A. 
     
     
         14 . The method of  claim 13  wherein said probe comprises a portion which hybridizes with at least one exon contained in CDKN2A. 
     
     
         15 . The method of  claim 13  wherein said probe is about 40 bp in length. 
     
     
         16 . The method of  claim 14  wherein said probe is about 40 bp in length.