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Abstract
Grant Number: 1R43CA101421-01 PI Name: DUBENSKY, THOMAS W. PI Email: tom_dubensky@ceruscorp.com PI Title: VICE PRESIDENT, RESEARCH Project Title: Listeria-Based Vaccines for Ovarian Cancer Therapy Abstract: DESCRIPTION (provided by the applicant): Ovarian cancer causes the highest mortality rate among women with gynecologic malignancy, approximately 14,000 cancer deaths per year. Women with late-stage disease have a 2-year relapse rate of more than 50%, and a 5-year survival rate of less than 50%. The goal of this proposal is to identify the optimal configuration of a Listeria monocytogenes-based cancer vaccine encoding the tumor antigen mesothelin, for application as a targeted immunotherapy for ovarian cancer. Listeria is an intracellular bacterium that primes robust CD4+/CD8+ T-cell mediated responses, has striking potency in animal models of both infectious disease and cancer, and has been tested in healthy human volunteers. Mesothelin is a differentiation antigen that is expressed in 95% of ovarian cancers and lower levels in other cancers, but other than mesothelial cells, is not detected in diverse normal tissues, including normal ovaries. A panel of recombinant Listeria that express mesothelin fused to elements that augment antigen presentation will be derived, and tested for therapeutic efficacy in a newly-developed syngeneic mouse model that expresses mesothelin and recapitulates human ovarian cancer. Accomplishing these goals will set the stage in a Phase II SBIR for moving the project toward a clinical trial in women with advanced ovarian cancer.
Thesaurus Terms:
Listeria, differentiation antigen, neoplasm /cancer vaccine, ovary neoplasm, tumor antigen, vaccine development, vector vaccine
interferon gamma, interleukin 10, interleukin 12, membrane protein, plasmid
laboratory mouse
Institution: CERUS CORPORATION 2411 STANWELL DR CONCORD, CA 945204810 Fiscal Year: 2003 Department: Project Start: 01-APR-2003 Project End: 01-OCT-2003 ICD: NATIONAL CANCER INSTITUTE IRG: ZRG1