Use of protein biomolecular targets in the treatment and visualization of brain tumors

Abstract

The present invention relates to the use of proteins which are differentially expressed in primary brain tumor tissues, as compared to normal brain tissues, as biomolecular targets for brain tumor treatment therapies. Specifically, the present invention relates to the use of immunotherapeutic and immunoimaging agents which specifically bind to one or more of human proteins angiopoietin related protein 2 (ARP-2,) secreted protein acidic, rich in cysteine (SPARC,) c-met proto-oncogene (C-MET,) brevican (BEHAB,) CD-44 antigen (CD-44,) tetraspanin 3 (TSPN3,) pleiotrophin (PTN,) osteopontin (OPN,) vasoactive intestinal peptide receptor-2 (VIPR-2,) and receptor protein tyrosine phosphatase zeta (PTPζ) for the treatment and visualization of brain tumors in patients. The present invention also provides compounds and pharmaceutically acceptable compositions for administration in the methods of the invention. The present invention also provides novel splice variants of protein PTPζ, PTPζ SM1 and PTPζ SM2. Nucleic acid probes specific for the spliced mRNA encoding these variants and affinity reagents specific for the novel proteins are also provided.

We claim:  
     
         1 . A method to treat a brain tumor comprising administering a therapeutic amount of a composition comprising: 
 a compound of the general formula α(VIPR2), wherein α(VIPR2) is one or more moieties which specifically binds to a human vasoactive intestinal peptide receptor-2, wherein the binding of α(VIPR2) alters the function of the vasoactive intestinal peptide receptor-2,    and a pharmaceutically acceptable carrier.    
     
     
         2 . The method of  claim 1  wherein the therapeutic composition is administered by intrathecal administration.  
     
     
         3 . The method of  claim 1  wherein the therapeutic composition is administered by intravascular administration.  
     
     
         4 . The method of  claim 1  wherein the brain tumor is a glioblastoma.  
     
     
         5 . The method of  claim 1  wherein α(VIPR2) is selected from the group consisting of an antibody and an antibody fragment.  
     
     
         6 . The method of  claim 1  wherein the composition is administered as a single dose.  
     
     
         7 . The method of  claim 1  wherein the composition is administered as a series of doses over a period of time.  
     
     
         8 . The method of  claim 1  wherein α(VIPR2) further comprises attached thereto one or more cytotoxic moieties C.  
     
     
         9 . The method of  claim 8  wherein the therapeutic composition is administered by intrathecal administration.  
     
     
         10 . The method of  claim 8  wherein the therapeutic composition is administered by intravascular administration.  
     
     
         11 . The method of  claim 8  wherein the brain tumor is a glioblastoma.  
     
     
         12 . The method of  claim 8  wherein α(VIPR2) is selected from the group consisting of an antibody and an antibody fragment.  
     
     
         13 . The method of  claim 8  wherein C is a radioactive moiety.  
     
     
         14 . The method of  claim 8  wherein C is a chemotoxic moiety.  
     
     
         15 . The method of  claim 8  wherein C is a toxin protein moiety.  
     
     
         16 . The method of  claim 8  wherein the composition is administered as a single dose.  
     
     
         17 . The method of  claim 8  wherein the composition is administered as a series of doses over a period of time.