Firing Up the Tumor Microenvironment in Metastatic Prostate Cancer with Synergistic PSMA-Targeting Radioligands and STING Agonist Nanotherapies
Abstract
Despite the availability of multiple types of treatment for metastatic prostate cancer, treatment outcomes for this patient population remain poor. Therefore, there is an urgent and unmet clinical need to develop new therapy approaches, including by combining different types of therapies together, to manage this lethal disease. One promising type of therapy being explored for multiple types of cancer in the past decade is immunotherapy. This type of therapy harnesses the patient’s own immune system to attack tumor cells. However, despite the promise of immunotherapy, studies to date in metastatic prostate cancer have not been particularly successful. The exact reason for this remains unclear, but one emerging thought for this poor efficacy is that metastatic prostate cancer is immunologically cold, with limited stimulation and infiltration of activated immune cells into tumor lesions to act on cancer cells. Scientists have explored methods to improve the effects of immunotherapies in metastatic tumor lesions, including using radiation and other drugs to stimulate the immune system. It is likely that successful management of metastatic prostate cancer will require a combination therapy approach. The objective of this study is to combine a promising systemic radiation therapy for prostate cancer called 177Lu-PSMA-617 with nanoparticles containing powerful immune system stimulating agents called STING-agonists to create a combination therapy approach that is more efficacious than either drug treatment alone. Given our prior experience with other types of radiation therapy, we believe that 177Lu-PSMA-617 will modify metastatic prostate cancer lesions environment to allow improved delivery of drug-containing nanoparticles and allow more anti-tumor immune cells to infiltrate the tumor. Together then, we anticipate that combination 177Lu-PSMA-617 radiation therapy with STING-agonist nanoparticles will be a promising treatment approach for metastatic prostate cancer, making these normally cold tumors hot to the body’s immune system. 177Lu-PSMA-617 is currently in late-stage clinical trials, while STING-agonists and nanoparticles similar to those to be tested in this study have also been tested in patients. Therefore, the approaches that we developed in this study will be immediately testable in patient studies. Furthermore, the outcome of this study will provide vital information about how systemically delivered radiation therapy affects the tumor immune system in prostate cancer and inspire new ways to combine other types of therapies with radiation, such as with antibodies or chemotherapies. I am a board-certified radiologist and nuclear medicine physician-scientist. I routinely interpret images of patients with prostate cancer and administer systemic radiation therapies to treat metastatic prostate cancer. With the imminent Food and Drug Administration approval of 177Lu-PSMA-617 and other PSMA-PET scans, management of prostate cancer will become an even more significant component of my clinical practice. My career objective is to develop a multidisciplinary bench to bedside research program that links my clinical practice of nuclear medicine/radiology with research into treatment strategies (especially involving systemic radiation therapy) for metastatic prostate cancer. I envision working with my colleagues in oncology, radiation oncology, and urology to conduct clinical trials to test out strategies we develop in the laboratory. Being a radiologist, I also aim to develop imaging tests that will be able to monitor the efficacy of these treatment strategies. The proposed research and career development plan will be vitally important for my career development to achieve my career objective. The Award will give me the protected time and mentored guidance to develop my research expertise in systemic radiation therapies as well as radiation immunology. This will not only be important for this project
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210061
Entities
People
- S. C. Thomas Ng
Organizations
- Massachusetts General Hospital
- United States Army