Enhancing Prostate Cancer Immunotherapy through Epigenetic Reprogramming for Optimal Activation of Specific Effector T-cells
About Enhancing Prostate Cancer Immunotherapy through Epigenetic Reprogramming for Optimal Activation of Specific Effector T-cells
- Immunotherapies that target immune-system inhibiting molecules called “checkpoint inhibitors” such as PD-1 can lead to complete and durable tumor regression in subsets of patients with multiple types of solid tumors, but have not been successful in prostate cancer. Identifying methods to enhance the efficacy of checkpoint blockade immunotherapy is critical.
- Epigenetic therapies are a class of therapies that can reprogram gene expression profiles in cells and may result in enhanced immune system functions.
- Dr. Drake and team are studying whether epigenetic therapies can reprogram the immune system in a way that promotes anti-tumor immune activity and will allow checkpoint blockade immunotherapy to become effective in prostate cancer patients.
- The effect of epigenetic therapies on expression of genes involved in recognition by the immune system will be determined in prostate cancer cells. Additionally, the effect of epigenetic therapies on the gene expression profiles and the functions of immune cells will be determined in mouse models of prostate cancer. These studies will indicate if epigenetic therapies can reprogram tumor and/or immune cells to promote anti-tumor immune responses.
- It will also be determined whether epigenetic therapies can prevent or reverse immune system tolerance against tumor cells. Tolerance is a natural autoimmunity-preventing program that tumor cells hijack.
- Finally, the combination of checkpoint blockade immunotherapy (anti-PD-1) and epigenetic therapy will be tested in preclinical prostate cancer models.
What this means for patients: Enhancing the efficacy of immunotherapies may lead to the development of long term clinical responses in prostate cancer patients. Dr. Drake and team will determine whether epigenetic therapies have the potential to render prostate cancer patients responsive to checkpoint blockade immunotherapy. If successful, this project will lead to a new combination therapy with curative potential.
Charles Drake, MD, PhD (Johns Hopkins University)
Stephen Baylin, MD (Johns Hopkins University), Vasan Yegnasubramanian, MD, PhD (Johns Hopkins University), William Nelson, MD, PhD (Johns Hopkins University), Michael Haffner, MD, PhD (Johns Hopkins University), Angelo De Marzo, MD, PhD (Johns Hopkins University), Charles Bieberich, PhD (University of Maryland, Baltimore County)