Prostate SPORE Projects

The translational research objectives of the SPORE are directed by five research projects:

Project 1: Utility of serum and tissue biomarkers for predicting response to androgen deprivation therapy in the population of men with rising PSA following definitive treatment

Principal Investigator: George G. Klee, M.D., Ph.D.

Dr. Klee and his colleagues Robert B. Jenkins, M.D., Ph.D.; Brian J. Davis, M.D., Ph.D.; Charles Y. F. Young, Ph.D.; and George Vasmatzis, Ph.D.; are combining their expertise in molecular biology, cell biology, genetics, clinical chemistry and the clinical management of prostate cancer patients to identify novel markers of prostate cancer and to develop assays for detecting these markers. Recently, their major focus has been to identify cohorts of patients, which can be used to validate these markers.

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Project 2: Prostate Imaging by Vibro-acoustography

Principal Investigator: Mostafa Fatemi, Ph.D.

Dr. Fatemi's team, which includes James F. Greenleaf, Ph.D.; Azra Alizad, M.D.; Farid G. Mitri, Ph.D.; Torrence M. Wilson, M.D.; Dr. Davis; Bernard F. King, M.D.; and Thomas J. Sebo, M.D.; is investigating the potential of a novel imaging technique called vibro-acoustography for prostate imaging. Their preliminary studies demonstrate that vibro-acoustography offers several key features that are important in the detection and treatment of prostate cancer. In particular, this method is sensitive to tissue stiffness, thus can be used to detect prostate tumors that are stiffer that the normal tissue. This method is also very sensitive to the presence of calcifications. It is expected that the performance of vibro-acoustography will be superior to that of conventional trans-rectal ultrasound imaging with regard to detection of malignant lesions and with respect to some aspects of guiding minimally invasive prostate procedures. Current ongoing efforts in the development of a surface vibro-acoustic probe for applications in breast cancer funded by the Department of Defense serve as important initial efforts from which this research in prostate imaging will benefit.

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Project 3: Gene Therapy of Prostate Cancer Using Radioactive Iodine

Principal Investigator: John C. Morris, III, M.D.

Dr. Morris and his fellow researchers Richard G. Vile, Ph.D.; Dr. Davis; Mark J. Federspiel, Ph.D.; and Dr. Wilson are studying a novel method of killing prostate cancer cells with radioiodine. The studies are a collaboration of a group of investigators with widely varying background and expertise. Dr. Morris has focused most of his career on thyroid diseases. He has considerable clinical experience in the use of radioiodine for therapy and diagnosis of thyroid diseases. He also has considerable experience in laboratory investigation involving thyroid cells, radioiodine, and thyroid molecular and cell biology, especially that involving thyroidal iodine uptake. As a logical extension of his thyroid focus, he has become interested in the potential use of the thyroidal iodide transporter as a potential therapeutic gene for therapy of non-thyroidal tumors because of its potential importance and because of the exciting success of his preliminary studies.

Dr. Vile, a co-investigator on the proposal, is a member of the Mayo Molecular Medicine Program and an expert in cancer gene therapy and vector development. Esteban Celis, M.D., Ph.D.; an immunologist and co-investigator who is already funded by the NIH for study of the immunology of prostate cancer, will contribute expertise in the evaluation of the immune responses to radioiodine therapy of prostate cancer. Donald J. Tindall, Ph.D.; and Dr. Young have contributed to preliminary results through their expertise with prostate cancer cells and the PSA promoter. Both will serve as consultants on the project. Because the collection of expertise and technology required for the conduct of these studies on a single campus is rare, Mayo's ability to perform them is relatively unique. Susan M. Geyer, Ph.D.; will participate in data analysis and experimental design, utilizing her experience as statistician for the Mayo Cancer Center and Biostatistics Core Director for the University of Iowa/Mayo Clinic Lymphoma SPORE.

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Project 4: A Randomized Phase II Clinical Trial to Determine the Safety, Tolerability and Efficacy of an Allogeneic Whole Cell Vaccine Administered With or Without Autologous Myeloid Dendritic Cells to Patients Suffering From Androgen Independent Prostate Carcinoma

Principal Investigator: Stanimir Vuk-Pavlovic, Ph.D.

Dr. Vuk-Pavlovic's team includes Allan B. Dietz, Ph.D.; Patrick A. Burch, M.D.; Eugene D. Kwon, M.D.; and Dennis A. Gastineau, M.D. They are developing a novel cellular vaccine for the treatment of prostate cancer. In collaboration with St. George's Hospital Medical School, London, England, they are implementing clinical–grade manufacturing of the vaccine, design and performance of a clinical trial, immunological monitoring, and integration and combined interpretation of clinical and monitoring data for future refinement of the protocol.

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Project 5: An Immune-Based Therapeutic Approach for Prostate Cancer

Principal Investigator: Esteban Celis, M.D., Ph.D.; H. Lee Moffitt Cancer Center

In an inter-institutional collaborative effort, encouraged by the SPORE program and designed to maximize expertise, Dr. Celis joins Dr. Kwon from Mayo Clinic to collaborate on a study of the capacity of synthetic peptides to induce cytotoxic and helper T lymphocyte responses to prostatic-associated antigens as a means of developing specific immunotherapy for prostate cancer. Dr. Celis has demonstrated that tumors can evade CTLs by masking their Major Histocompatibility Complex Class I molecules. Dr. Celis is also collaborating with Drs. Kwon and Vile to characterize the immune involvement in cell killing that is induced by their vector constructs and to determine the effect of androgens on this response.

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