Evaluation of Immune-based Combinations in Prostate Cancer

Division Of Basic Sciences - Nci

Investigators

Linked publications, trials & patents

Abstract

Current studies are exploring a combination of standard of care chemotherapy with an immunocytokine combination treatment. 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. We have completed the phase 1 portion of 21-c-0001, which has established a safe dose of docetaxel with M9241. We will now explore immune responses in this study as we move into the phase 2 portion of the study that will focus on metastatic castration resistant prostate cancer. We are also about to open a new study combining M9241 and radiation in patients with newly diagnosed and localized prostate cancer in a collaboration with the Radiation Oncology Branch. This is based on the potential synergy of radiation and M9241 established in preclinical models.