CAR T cell immunotherapy for the treatment of prostate cancer

Immunotherapies have transformed the treatment of many cancers, but not prostate cancer. Chimeric-antigen receptor (CAR) T cell therapy, in which a patient's own T cells are genetically modified to target tumour-associated antigens, have greatly improved clinical outcomes for a subset of cancers, predominantly blood cancers. However, success in treating solid tumours has been limited. One of the main factors contributing to poor outcomes is the immunosuppressive tumour microenvironment, which prevents CAR T cell infiltration into the tumour and an effective immune response. To increase the efficacy of CAR T cell therapy, there are two primary approaches: 1) The use of next-generation CAR T cells that are engineered to enhance the anti-tumour immune response; and 2) Therapeutically modulating the tumour microenvironment to promote T cell recruitment and activity. This project will integrate both approaches, with the aim of identifying strategies to improve the efficacy of CAR T cell therapy for the treatment of prostate cancer. This project will use patient-derived models of prostate cancer, such as xenografts and organoids, to investigate treatment responses to CAR T cell therapy in diverse prostate tumours. We will also explore the mechanisms that contribute to treatment sensitivity and resistance. Students will gain expertise in preclinical experiments, cancer biology and tumour pathology. Techniques may include immunohistochemistry, flow cytometry and bioinformatics. This work will be performed in collaboration with scientists, clinicians and patient advocates.