Compositions and Methods of Treating Tumors

Abstract

Methods of treating an individual who has an erbB protein mediated tumor is disclosed. Methods of preventing erbB protein mediated tumors in an individual are disclosed. The methods comprise administering to the individual a nucleic acid molecule that encodes a protein that dimerizes with an erbB protein and that is deficient in tyrosine kinase activity. Composition that comprise such nucleic acid molecules including pharmaceutical compositions are disclosed.

1 - 45 . (canceled) 
     
     
         46 . A method of treating an individual who has an erbB protein-mediated tumor, which method comprises the steps of:
 (a) administering to the individual an active agent that disrupts tyrosine kinase activity associated with multimeric receptor ensembles in a tumor cell of said erbB protein-mediated tumor,
 wherein said active agent is selected from the group consisting of an EGFR antibody and a non-proteinaceous kinase inhibitor, and wherein said active agent has a cytostatic effect on said tumor cell; and 
 wherein said multimeric receptor ensembles comprise EGFR heterodimers; and 
   (b) thereafter exposing said individual to a therapeutic amount of chemotherapy, wherein said chemotherapy is administered 24-72 hours after administration of the active agent.   
     
     
         47 . The method of  claim 46 , wherein said active agent inhibits formation of erbB protein dimers that produce elevated tyrosine kinase activity in said tumor cell. 
     
     
         48 . The method of  claim 46 , wherein said active agent inhibits tyrosine kinase activity associated with dimer formation. 
     
     
         49 . The method of  claim 46 , wherein said active agent inhibits tyrosine kinase activity associated with EGFR. 
     
     
         50 . The method of  claim 46 , wherein said EGFR heterodimers are selected from the group consisting of p185/EGFR heterodimers, p165/mutant EGFR heterodimers, and EGFR/mutant EGFR heterodimers. 
     
     
         51 . The method of  claim 46 , wherein the active agent is administered by intratumoral, intravenous, intraarterial, subcutaneous, intradermal, or intramuscular administration. 
     
     
         52 . The method of  claim 46 , wherein cells of said tumor express EGER which is ligand-independent. 
     
     
         53 . The method of  claim 46 , wherein cells of said tumor overexpress ErbB receptors. 
     
     
         54 . The method of  claim 46 , wherein said individual has undergone prior surgical intervention on said tumor. 
     
     
         55 . The method of  claim 46 , wherein said chemotherapy comprises administering a cytotoxic chemotherapeutic agent.