Research: 2018 – Saskatoon

Project Title:
Eradication of localized prostate cancer by irreversible electroporation ablation combined with immunotherapy via converting tolerogenic tumor microenvironment.
Investigators:
Jim Xiang, M.D., Ph.D, Department of Oncology, College of Medecine, University of Saskatchewan

Dr. Jim Xiang is a Senior Research Scientist at the Saskatchewan Cancer Agency (SCA), Professor, Division of Oncology, College of Medecine, University of Saskatchewan since 1996. Dr. Xiang received his M.D. at the Shanghai University of Medecine in 1970, and obtained his M.S. in 1983 and Ph.D. in 1986 at the University Florida. He did two-year postdoctoral work (1986-1988) at the National Cancer Institute, NIH, USA, and did another two-year postdoctoral work (1986-1988) at the University of Toronto, Canada. Subsequently, Dr. Xiang started his independent cancer research at the SCA and the University of Saskatchewan in 1990. Since then, Dr. Xiang has obtained more than 50 research grant Awards with a total ~9.1 million dollars and published more than 220 publications in peer-reviewed journals.

Project Abstract:
Prostate cancer (PC) is the second leading cause of cancer death in men. In immune system, CD8+ cytotoxic T lymphocytes (CTL) play a critical role in fighting against tumor. A new technology called irreversible electroporation (IRE) has been applied for cancer ablation therapy. Immune adjuvant CpG and PD-1 blockade have been shown to boost antitumor CTL responses. In this study, we will establish an animal model bearing localized mouse PC, that mimics prostate cancer patients. We will assess the therapeutic effect of IRE ablation combined with immunotherapy of CpG adjuvant and PD-1 blockade against localized PC in our animal model. Finally, an optimal protocol of IRE combined with immunotherapy derived from our animal studies will be developed, which has the potential to benefit for clinical IRE therapy for PC patients.
Scientific Abstract:
Prostate cancer (PC) is the second leading cause of cancer death in men. In immune system, CD8+ cytotoxic T lymphocytes (CTL) play a critical role in fighting against tumor. A new technology called irreversible electroporation (IRE), that generates numerous nano-holes in cellular membrane leading to tumor cell apoptosis, has been applied for cancer ablation therapy. The IRE-induced apoptotic dead tumor cells can be targets for the immune system to ‘learn’ how to seek and destroy tumor cells within the initial tumor, but also against tumor cells that have spread elsewhere (metastases). Immune adjuvant CpG and PD-1 blockade have been shown to boost antitumor CTL responses. In this study, we will establish an animal model bearing localized mouse PC, that mimics prostate cancer patients. We have recently constructed a custom-made IRE device. We will assess the therapeutic effect of IRE ablation combined with immunotherapy of CpG adjuvant and PD-1 blockade against localized PC in our animal model. Finally, an optimal protocol of IRE combined with immunotherapy derived from our animal studies will be developed, which has the potential to benefit for clinical IRE therapy applied in Saskatoon for PC patients.
Impact on prostate cancer patients:
IRE is a new technique in ablation therapy strategies, that has an advantage of preserving blood vessels and nerves in the ablation region. We will, for the first time, develop an optimal IRE therapy with CpG and PD-1 blockade for enhancing IRE-induced CTL responses leading to more efficient inhibition of prostate cancer. Therefore, this project is not only novel, but also is of clinical relevance since the optimal protocol developed in our animal model can be directly translated into clinical practice for IRE therapy of prostate cancer patients as well as other patients with unresectable cancers such as pancreatic and liver cancers.