Posted February 27, 2014
Philip Thorpe, Ph.D., Professor of Pharmacology
Yi Yin, M.D., Ph.D., Assistant Instructor in Urology
University of Texas Southwestern Medical Center
Currently, there is no cure for prostate cancer once it has spread throughout the body. A number of treatments are in use, the most common being reduction of the male sex hormones (androgens) needed by the cancer cells for survival and growth. However, this treatment only works temporarily, as mutant cancer cells eventually develop mechanisms to bypass this treatment and the cancer recurs.
To overcome this problem, Drs. Philip Thorpe and Yi Yin, with funding from Fiscal Year 2005 (FY05) and FY08 PCRP Idea Development Awards, found a way to "arm" the immune system so it can recognize the mutant cancer cells and destroy them. The PIs developed an immune activating antibody that, when used in combination with hormone deprivation therapy (HDT), resulted in lifelong cures in 40% of treated mice with prostate cancer. HDT induces oxidative stress in the tumor microenvironment, which, in turn, causes exposure of phosphatidylserine (PS) on tumor blood vessels and tumor cells. This new antibody targets PS on tumor blood vessels, enabling immune cells to destroy the tumor without affecting normal tissue, and Drs. Thorpe and Yin observed that treated animals developed immunity to their tumors. This led to the investigators' discovery that PS in the tumor microenvironment prevented immune cells from functioning. Treatment with the PS-targeting antibody reactivated tumor immunity, preventing the tumors from re-growing and metastasizing.
Although a number of benchmarks must be reached before this antibody can be approved for treating prostate cancer patients, the process is up and running. In fact, Peregrine Pharmaceuticals, Inc., is already testing a semi-human version of the antibody, called bavituximab, in multiple clinical trials. Taken together, the present studies provide the foundation for combining bavituximab with hormone deprivation therapy to treat prostate cancer.
Program Note: We are very sad to report that Dr. Thorpe passed away on March 30, 2013. Dr. Thorpe was an extraordinary scientist held in high regard by his peers and collages for his significant contributions to field of immunotherapy and pharmaceutical development. Dr. Thorpe held the Serena S. Simmons Distinguished Chair in Cancer Immunopharmacology and was a Professor of Pharmacology at University of Texas, Southwestern. He was also a scientific advisor and member of the scientific resource board at Peregrine Pharmaceuticals. We are indebted to Dr. Thorpe for his tireless effort to develop treatments that improve the outcomes of all cancer patients, including those afflicted with prostate cancer. Additional information is provided at Peregrine Pharmaceuticals, Inc. Philip E. Thorpe In Memoriam and UT Southwestern Philip E. Thorpe In Memoriam.
Yi Yin, Xianming Huang, Kristi D. Lynn, and Philip E. Thorpe. Phosphatidylserine-Targeting Antibody Induces M1 Macrophage Polarization and Promotes Myeloid-Derived Suppressor Cell Differentiation. Cancer Immunol Res October 2013 1:256-268; Published OnlineFirst August 19, 2013; doi:10.1158/2326-6066.CIR-13-0073
Public and Technical Abstracts: Targeting Phosphatidylserine to Improve Hormone Therapy of Prostate Cancer
Public and Technical Abstracts: Vascular Targeting Antibodies for Improving Chemotherapy of Prostate Cancer