Head
Professor Pei Xiang Xing, MB, MM, PhD
Staff
Dr Xiu Feng Hu, MB, MM, PhD
Mr Scott Vandervalk, BSc(Hons)
Students
Dr Jie Li, PhD
Ms Eunice Yang, BSc(Hons), PhD
Research Overview
The aim of our research is to develop effective strategies to treat cancers, especially the prostate and breast cancers by immunological approaches: firstly to activate the immune system by vaccination using three unique oncoproteins Cripto, Pim-1 and MUC1 (active immunotherapy) and secondly by making monoclonal antibodies (mAbs), a new treatment for prostate cancer (passive immunotherapy). Although our principal focus is prostate and breast cancer, we are also evaluating the possible use of these strategies in other malignancies, such as colon cancer and leukaemia.
In addition, we have produced mAbs to Cripto and Pim-1 that showed significant inhibitory effects on the growth of human prostate cancer, with these effects enhanced by cytotoxic drugs and small molecule inhibitor. Immunisation using Cripto and Pim-1 as antigens also induced immune responses and showed protective effects in mice. The mechanisms of the mAb-targeted therapy is being studied and demonstrated that the mAbs interrupted several signalling transduction pathways that lead to the cancer cell death (apoptosis). The research results suggest that the two oncoproteins Cripto and Pim-1 may be used as novel targets to treat or prevent prostate and breast cancers, and leukaemia. Anti-MUC1 mAbs have also been produced, which also showed therapeutic effect. The mAbs are being studied for the treatment of breast cancer by mAb alone and combination of the mAbs and inhibitor. The anti-Pim-1 mAb is also being humanised, which could be a potential for future clinical trials.
Research Objectives
• To treat prostate cancer in mouse models by targeting oncoproteins Pim-1, Cripto and MUC1 and studying active and passive immunotherapy
• To study signal transduction pathways and apoptosis induced by anti-oncoprotein antibodies
• To treat the malignant diseases such as breast cancer, colon cancer and leukaemia by combination of monoclonal antibodies and small molecule inhibitor
Research Highlights
• Combination of the anti-Cripto, anti-Pim-1 and anti-MUC1 mAbs and a small molecule inhibitor synergistically inhibited cancer cell growth
• Immunisation of mice using Pim-1 as antigen showed inhibition of tumour growth suggesting that Pim-1 is a unique target for vaccination to treat prostate cancer
• Demonstrated that the anti-Pim-1 mAbs inhibited proliferation of T lymphocytes by targeting upregulated Pim-1
• Demonstrated that anti-Pim-1 mAb down regulated Pim-1 expression and interrupted Akt signalling transduction pathways, and induced cancer cell death through mitochondrial death pathway