Antitumor effect of mutant bik

Abstract

The present invention regards mutant forms of Bik that comprise anti-cell proliferation and/or pro-apoptotic activities. In particular embodiments, the Bik polypeptides comprise a substitution at Thr33 and Ser35 and, in some embodiments, phosphorylation at these sites is inhibited. In more particular embodiments, these forms are useful for cancer therapy, particularly when administered in combination with liposomes. In embodiments wherein a mutant Bik polynucleotide is administered for cancer therapy, the polynucleotide may be regulated in a tissue-specific manner.

1 .- 75 . (canceled) 
     
     
         76 . A method of inducing anti-tumor activity, anti-cell proliferation activity, and/or pro-apoptotic activity in a subject, comprising administering to the subject an effective amount of a mutant Bik polypeptide having an altered amino acid sequence, said polypeptide comprising:
 a) SEQ ID NO:7, SEQ ID NO:8, or SEQ ID NO:9; or   b) polypeptides having sequence that is between 91% and 99% identical to SEQ ID NO:7, SEQ ID NO:8, or SEQ ID NO:9, said polypeptides having a mutation at Thr 33 , Ser 35 , or both Thr 33  and Ser 35 .   
     
     
         77 . The method of  claim 76 , wherein the polypeptide further comprises a protein transduction domain. 
     
     
         78 . The method of  claim 76 , wherein the subject is a human. 
     
     
         79 . The method of  claim 78 , wherein the human has a proliferative cell disorder. 
     
     
         80 . The method of  claim 79 , wherein the proliferative cell disorder is cancer. 
     
     
         81 . The method of  claim 80 , wherein the cancer is breast cancer, prostate cancer, ovarian cancer, sarcoma, lung cancer, brain cancer, pancreatic cancer, liver cancer, bladder cancer, gastrointestinal cancer, leukemia, lymphoma, or myeloma. 
     
     
         82 . The method of  claim 80 , wherein the cancer is estrogen receptor positive, is EGF receptor overexpressing, is Her2/neu-overexpressing, is not Her-2/neu-overexpressing, is Akt overexpressing, is angrogen independent, or is androgen dependent. 
     
     
         83 . The method of  claim 80 , wherein the cancer is a solid tumors, such as, for example, sarcoma, lung, brain, pancreatic, liver, bladder, gastrointestinal cancers, or hematologic malignancies, such as leukemia, lymphoma, and myeloma 
     
     
         84 . The method of  claim 79 , wherein the proliferative cell disorder is restenosis. 
     
     
         85 . The method of  claim 76 , wherein the polypeptide is comprised in pharmacologically acceptable excipient. 
     
     
         86 . The method of  claim 76 , wherein the polypeptide is complexed with a lipid. 
     
     
         87 . The method of  claim 76 , further defined as a method of preventing growth of a cell in an individual.