Evaluation of Immune-based Combinations in Metastatic Prostate Cancer

Division Of Basic Sciences - Nci

Investigators

Linked publications, trials & patents

Abstract

This includes the evaluation of immunotherapy in patients with newly diagnosed metastatic castration sensitive prostate cancer who an be treated with docetaxel. This also includes patients with metastatic castration resistant prostate cancer who can be treated with a number of therapies including enzalutamide. Both agents have been previously combine with prostvac, a therapeutic cancer vaccine. This is based on preclinical data suggesting synergy with both combinations. Several studies have now completed accrual and are in the follow-up phase for final data analysis. New planned studies will open in the coming months including combinations of standard of care chemotherapy with an immunocytokine combination treatment. In addition, new studies are in development including combinations of standard radiation therapy with an immunocytokine combination treatment. Finally another study will combine a radiopharmaceutical with a PARP inhibitor and an immune checkpoint inhibitor. A new focus involves the novel evaluation of immunocytokines in prostate cancer. Unlike checkpoint inhibitors which may require T-cell infiltration or high tumor mutational burden to be effective, cytokines provide an opportunity to impact multiple immune cell lines within the prostate cancer microenvironment and convert them broadly from immune suppressive to a more anti-tumor phenotype. Indeed, cytokines have been a key part of immune treatments for kidney cancer and melanoma before the development of checkpoint inhibitors, but the potential systemic toxicity of high doses of cytokines often limited treatment delivery and thus efficacy. Immunocytokines are able to deliver smaller doses of cytokines in a targeted fashion to the tumor microenvironment, thereby limiting systemic toxicity and perhaps enhancing clinical efficacy. NHS-IL12 (M9241) has been developed clinically within the GMB Immunotherapy Section and specifically targets histones of exposed DNA in necrotic tissue. This capability forms the basis of a key strategy within my research program. By using standard therapies for prostate cancer such as radiation and chemotherapy to induce necrosis, the goal is to use NHS-IL12 to alter the pleiotropic immune microenvironment, including multiple immune cell populations, shifting it to a more anti-tumor phenotype. I feel there are opportunities to use this strategy in early disease (with radiation) and late stage disease (with chemotherapy). .