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Abstract
Grant Number: 1R43CA124001-01A2 Project Title: p53 Fusion Protein as an Oncology Therapeutic
PI Information: Name Title LIN, XINLI lin@proteomtech-inc.com Abstract: DESCRIPTION (provided by applicant): The aim of this proposal is to test the feasibility of the use of a p53 fusion protein as a cancer therapeutic. World wide 10 million people are diagnosed every year with cancer. 50% of human cancers involve a mutation in the p53 gene. In addition, these mutations are frequently found in solid tumors that are resistant to conventional therapies. These facts clearly demonstrate that p53 is an important target for anti-neoplastic therapies. Development of a novel p53- targeted anti-neoplastic therapeutic has the potential to save millions of lives worldwide each year, yet there are currently no FDA approved cancer therapies targeting this gene product. Using a patented refolding technology developed at ProteomTech, Inc., Pt-Fold, we have identified conditions that allow us to produce large amounts of stable tetrameric recombinant human p53 protein. To our knowledge, we are the only group that has been successful in accomplishing this. However, an efficient means of delivering this protein into cells is required for a successful protein therapeutic. We propose to achieve intracellular delivery by producing a form of p53 that is fused to a peptide that will mediate cell entry. Feasibility issues that will be addressed in phase 1 of this application include expression, refolding, purification and functional testing of the fusion proteins in p53-deficient cancer cell lines. Our goal of phase I of the proposal is to identify the best fusion protein for pre-clinical studies for a Phase II application. Development of a novel anti-neoplastic therapeutic for cancers that are characterized by a mutation if p53 and refractory to current therapies would represent a significant contribution to the oncology field and has the potential to benefit millions of people each year. According to the International Agency for Research on Cancer (IARC), world wide 10 million people will be diagnosed every year with cancer. Furthermore, the IARC estimated that up to half of all human cancers carry an inactivating mutation in the p53 gene. P53 mutations are frequently found in solid tumors that are resistant to conventional therapies. Despite the importance of this target, there are currently no FDA approved cancer therapies targeting p53. The aim of this proposal is to test the feasibility of the use of a p53 fusion protein as a novel cancer therapeutic.
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Institution: PROTEOMTECH, INC. 5980 HORTON ST, STE 405 EMERYVILLE, CA 94608 Fiscal Year: 2007 Department: Project Start: 18-SEP-2007 Project End: 31-AUG-2008 ICD: NATIONAL CANCER INSTITUTE IRG: ZRG1