Genitourinary Cancer Research

Brendan D. Curti, M.D., serves as medical director of Providence Biotherapy Program at Providence Cancer Center and Genitourinary Cancer Research at the Robert W. Franz Cancer Research Center in the Earle A. Chiles Research Institute at Providence Cancer Center. His clinical research focuses on developing new immunotherapies to treat prostate carcinoma, renal cell carcinoma, bladder cancer and melanoma. Providence Biotherapy Program treats patients with kidney cancer and melanoma and is one of the busiest of its kind in the country.

Dr. Curti earned his medical degree from Georgetown University, where he also completed a fellowship in medical oncology. He served as a senior investigator in the Biological Response Modifiers Program at the National Cancer Institute. Dr. Curti was also an associate professor at the Penn State College of Medicine before joining Robert W. Franz Cancer Research Center. In addition to his medical director responsibilities, Dr. Curti is a medical oncologist at Providence Cancer Center Oncology and Hematology Care Clinic - Eastside.

Current Projects
Dr. Curti is actively developing new immunotherapy strategies in a variety of cancers. Examples of this work include:

Anti OX-40
Dr. Curti is the principal investigator for a National Institutes of Health grant that funded a phase I clinical trial using anti-OX40 antibody. Anti-OX40 enhances T-cell memory and function. Providence Cancer Center is the first research institute in the world to test anti-OX40 in clinical practice and began enrolling patients in March, 2006.  The phase I study is completed and has shown promise in stimulating immune responses in patients, as well as regression of some tumors.  Other OX40-based clinical trials will be opening soon including the combination of anti-OX40, chemotherapy and radiation in men with advanced prostate cancer funded by the Prostate Cancer Foundation.

Vaccine Therapy in Prostate Cancer
Another significant translational research effort is the investigation of vaccines including sipuleucel-T (Provenge) and GVAX. Sipuleucel has recently been approved by the FDA, and the Robert W. Franz Cancer Research Center is one of the first 50 sites in the U.S. chosen to offer this innovative immunotherapy to men with advanced prostate cancer.  There are other open clinical research studies ongoing to understand the effect of sipuleucel on the immune system.  

GVAX is an allogeneic GM-CSF transfected prostate cancer cell line vaccine. Robert W. Franz Cancer Research Center colleagues Bernard A. Fox, Ph.D., and Hong-Ming Hu, Ph.D., showed enhanced vaccine responses during homeostatic expansion of lymphocytes after chemotherapy in preclinical animal models.  This concept had not been previously tested in humans. We performed and completed a phase I study that looked at GVAX with cyclophosphamide and fludarabine chemotherapy. One of the important findings of the study was that in humans, regulatory T cells (Treg) that suppress immune response, appeared after GVAX and chemotherapy.  Similar observations have been made by other cancer researchers examining other immunotherapies.  Other work by the Dr. Fox’s Laboratory of Molecular and Tumor Immunology showed that the Treg could be decreased using a medical procedure called leukapheresis and an iron-conjugated antibody to tag the Treg and remove them with the use of a magnet.  Another pilot study using GVAX, lymphopenia-inducing chemotherapy and Treg depletion is expected to open in the latter part of 2010.

Immunotherapy and Targeted Therapy in Kidney Cancer
Providence Biotherapy Program  is one of the busiest high-dose Interleukin-2 centers in the U.S.  There have been numerous clinical trials conducted through Providence Biotherapy Program in renal cancer.  A recent translational research project has been a collaboration between Dr. Curti and Steven Seung, M.D., Ph.D., of Providence Radiation Oncology Services to examine the immunological and clinical effects of stereotactic body radiation (SBRT) and Interleukin-2.  A pilot study showed encouraging clinical results and additional translational research is planned.

The Genitourinary Cancer Research program at Robert W. Franz Cancer Research Center has also contributed to the clinical development of vascular targeting agents in renal cancer including sunitinib, sorafenib, pazopanib, and temsirolimus.  These agents are now approved by the FDA, and have made a significant impact in the clinical care of patients with renal cancer.  Additional clinical research is planned using new combinations of vascular targeting agents and examination of their use in the adjuvant setting.      

Current Research Collaborations
OX40

Melanoma

  • Adoptive Cellular Therapy in Melanoma

Prostate

  • Development of effective immunotherapy for prostate cancer patients (DOD PC020094 – PI: Bernard A. Fox)
  •  Exploiting lymphopenia and depletion of CD25+ regulatory T cells to augment effective immunotherapy – PI: Bernard A. Fox
    • Clinical: 
      • Walter J. Urba, M.D., Ph.D., director cancer research, Robert W. Franz Cancer Research Center, Earle A. Chiles Research Institute, Providence Cancer Center
    • Lab:

 Full List of Publications