88kDa tumorigenic growth factor and antagonists

Abstract

The invention relates to products and methods for treating cancer and for diagnosing tumorigenicity and other diseases associated with alteration in GP88 expression or action. Antagonists to an 88 KDa autocrine growth and tumorigenicity stimulator are provided which inhibit its expression or biological activity. The antagonists include antisense oligonucleotides and antibodies.

What is claimed as new and desired to be protected by Letters Patent is:  
     
         1 . A pharmaceutical composition comprising a GP88 antagonizing agent and a pharmaceutically acceptable carrier.  
     
     
         2 . A composition according to  claim 1  wherein said agent is an anti-GP88 antibody.  
     
     
         3 . A composition according to  claim 2  wherein said antibody is a neutralizing antibody.  
     
     
         4 . A composition according to  claim 3  wherein said antibody is made against a GP88 sequence between aminoacid 334 and 362.  
     
     
         5 . A composition according to  claim 2  wherein said antibody is selected from the group consisting of anti-K19T, anti-S14R, anti-E19V and anti-A14R antibodies.  
     
     
         6 . A composition according to  claim 1  wherein said agent is an antisense oligonucleotide.  
     
     
         7 . A composition according to  claim 6  wherein said antisense oligonucleotide is an antisense RNA sequence having sufficient complementarity to GP88 mRNA to cause hybridization between said antisense RNA and said GP88 mRNA and inhibition of the translation of said GP88 mRNA.  
     
     
         8 . A composition according to  claim 6  wherein said antisense oligonucleotide is an antisense DNA sequence having sufficient complementarity to said GP88 mRNA to inhibit expression of said GP88.  
     
     
         9 . A composition according to  claim 1  wherein said agent is a vector suitable for expressing an antisense nucleotide sequence having sufficient complementarity to GP88 mRNA to inhibit expression of GP88 in cells.  
     
     
         10 . An expression vector containing cDNA to GP88 or a variant of GP88 capable of expressing GP88 protein, or a functional derivative of GP88 protein, substantially free of other mammalian proteins.  
     
     
         11 . A composition according to  claim 1  wherein said agent is a reagent that inhibits GP88 mRNA or protein expression.  
     
     
         12 . A composition according to  claim 1  wherein said agent is a reagent that inhibits GP88 protein secretion.  
     
     
         13 . A composition according to  claim 1  wherein said agent is an antibody to GP88 receptor that can block GP88 function.  
     
     
         14 . A composition according to  claim 1  wherein said agent is an antagonist that inhibits GP88 binding to its receptor.  
     
     
         15 . A method for treating diseases associated with increased expression of GP88 comprising the steps of administering an effective amount of a GP88 antagonizing agent wherein said agent inhibits the production or biological activity of GP88.  
     
     
         16 . A method according to  claim 15  wherein said disease is cancer.  
     
     
         17 . A method according to  claim 15  wherein said agent is an antisense oligonucleotide at least 20 nucleotides in length and having sufficient complementarity to GP88 DNA to inhibit GP88 expression.  
     
     
         18 . A method according to  claim 15  wherein said agent is antisense RNA.  
     
     
         19 . A method according to  claim 15  wherein said agent is an anti-GP88 antibody.  
     
     
         20 . A method for diagnosing tumorigenicity comprising the steps of measuring the level of GP88 expression in tissue extracts or biological fluids; measuring the level of GP88 expression in corresponding normal or peripheral tissues; and determining whether the measured level of GP88 expression in tissue extracts is higher than the level in corresponding normal or peripheral tissues.  
     
     
         21 . A method according to  claim 16  wherein said measuring step comprises measuring GP88 mRNA expression.  
     
     
         22 . A method according to  claim 16  where said measuring step comprises measuring GP protein expression.  
     
     
         23 . A method for diagnosing diseases associated with alteration in GP88 biological action comprising the steps of measuring GP88 binding to its cell surface receptors or measuring GP88 receptors expression.  
     
     
         24 . A method for treating diseases associated with alteration of GP88 biological activity comprising the steps of administering an effective amount of a GP88 antagonizing agent inhibits biological activity of GP88.  
     
     
         25 . A method according to  claim 24  wherein said agent is a neutralizing anti-GP88 antibody.  
     
     
         26 . A method according to  claim 24  wherein said agent is an antagonist of GP88 binding to its receptor.  
     
     
         27 . A method according to  claim 24  wherein said agent is an anti-GP88 receptor antibody.