C-Terminal p53 palindromic peptide that induces apoptosis of cells with aberrant p53 and uses thereof
Lead Inventors: Robert L. Fine; Paul Brandt-Rauf; Yueha MaoProblem or Unmet Need:More than 50% of human malignancies, including breast cancers, are associated with missense mutations or deletions of p53, a sequence-specific transcriptional factor involved in cell growth regulation. Therefore, a therapy directed at specifically killing p53-mutant cells would have wide application in targeted cancer therapies. The invention provides a method of killing cancer cells that contain aberrant p53 using a plasmid that expresses a specific peptide sequence. This polypeptide could induce p53-dependent, apoptotic cell death in the presence of mutant p53 with minimal effect on cells with normal levels of wild-type 53, which could be used for cancer chemotherapy or chemoprophylaxis. The invention identified two polypeptides comprising a given segment of continuous amino acids (SEQ ID NO: 1, SEQ ID NO: 2) or at least two of each covalently linked to each other. These polypeptides activate the DNA binding activity of p53 and thus activate the cellular functions of p53, enable their use as pharmaceutical compositions in a variety of therapeutic regimens, which permits the arrest of the growth or proliferation of tumor cells or apoptosis of tumor cells. The invention also defines the composition and the methods to systemically, or locally administer polypeptides to the site of the tumor.
Novel chemotherapeutic treatment targeted on aberrant p53, which has broad application on different cancers The advanced administration method is not affected by proteolytic extracellular breakdown and does not generate immune responses
Novel therapeutic pharmaceutical compositions and methods for aberrant p53 targeted anti cancer treatment Novel treatment for patients with cancer to enhance the tumor suppressor functions of p53, whether wild-type or mutant p53 is present in tumor cells
The invention identified two polypeptides comprising a given segment of continuous amino acids (SEQ ID NO: 1, SEQ ID NO: 2) or at least two of each covalently linked to each other. These polypeptides activate the DNA binding activity of p53 and thus ...
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