Maximizing Androgen Deprivation ImmunoGenICity through PD-1 and IL-8 Blockade in Lethal Prostate Cancer (MAGIC-8)

Immunotherapy is a promising type of cancer therapy that activates a patient’s own immune system to fight their cancer. Immunotherapy has been highly effective in some cancers such as melanoma and lung cancer, but has yet to be optimized for prostate cancer. Charles Drake and team are developing a new immunotherapy treatment regimen that can effectively activate anti-tumor immune responses in prostate cancer. The team previously discovered that prostate tumors secrete an immune suppressive protein, IL-8, especially during treatment with androgen deprivation therapy (ADT). Based on these findings, the team is conducting a clinical trial (MAGIC-8) which combines a novel IL-8-targeting treatment, with the immune activating therapy nivolumab, and ADT, in men with hormone-sensitive recurrent prostate cancer. In this project, the team will use samples from the patients on this trial to investigate key biological changes needed to re-establish anti-tumor immunity in prostate cancer and identify biomarkers that can predict treatment responses. The team will determine the impact of this immunotherapy combination treatment regimen on the types and numbers of immune cells infiltrating the tumor, including whether the treatment alters the balance between tumor-killing and tumor-promoting immune cell types. How this immunotherapy regimen affect the total body (systemic) immune system state will be investigated. Whether specific tumor mutations or expression of master cancer-driving proteins are associated with clinical responses to treatment with IL-8-blockade and nivolumab will be investigated. If successful. This project will result in the development of a new immunotherapy regimen that will extend the lives of patients, as well as uncover biology and biomarkers of treatment responses. What this means to patients: New strategies are needed in order to harness the power of the immune system as an effective therapeutic in men with prostate cancer. Dr. Drake and team are conducting a clinical trial testing a novel immunotherapy regimen that combines a drug that blocks immune suppression with a drug that enhances anti-cancer immune activity. This project will determine the clinical and biological effects of this treatment in patients, and develop biomarkers that can predict which patients are most likely to respond.