¹⁷⁷Lu-PSMA-617 as a Radioimmunotherapy for Prostate Cancer

Principal Investigators: Rahul Aggarwal, MD (University of California, San Francisco), Lawrence Fong, MD, (University of California, San Francisco), Michael Evans, PhD (University of California, San Francisco), Thomas Hope, MD (University of California, San Francisco)

Co-Investigators: David Oh, MD, PhD (University of California, San Francisco), Charles Craik, PhD (University of California, San Francisco), Li Zhang, PhD (University of California, San Francisco)

Description: 

• Immunotherapies are cancer treatments that activate a patient’s immune system to target and kill their cancer cells. Checkpoint immunotherapy has been extremely effective, even curative, in some patients with various cancer types, but has had efficacy in only a small number of prostate cancer patients thus far.  Strategies to enhance immunotherapy for prostate cancer are greatly needed.
• Radiation therapy (RT) has been shown to activate anti-tumor immune responses and may be synergistic in combination with immunotherapy.
• ¹⁷⁷Lu-PSMA-617 is in a promising new class of systemic radiation therapies, composed of a tumor-targeting molecule attached to a radioactive isotope, thus delivering radiation directly to tumor cells anywhere in the body.
• Rahul Aggarwal and team are studying whether and how ¹⁷⁷Lu-PSMA-617 may be synergistic with checkpoint immunotherapy.
• In this project, the team will study the effects of various types of radiation therapies alone or in combination with checkpoint immunotherapy in mouse prostate cancer models.
• A novel PET imaging technology to measure and visualize anti-tumor immune responses will be tested and validated in preclinical models.
• The team will study how ¹⁷⁷Lu-PSMA-617 alone or in combination with anti-PD1 checkpoint immunotherapy impacts the tumor microenvironment and anti-tumor immune responses using tumor and blood samples from patients on a clinical trial. The team will also investigate this in patients from trials testing combinations of checkpoint immunotherapy with radium-223 or stereotactic radiation (SBRT).  Whether any immune parameters correlate with patient outcomes and have potential as predictive biomarkers will be determined.
• If successful, this project will determine the optimal form of radiation therapy that can synergize with checkpoint immunotherapy to produce effective anti-tumor immune responses. The mechanisms by which this occurs will be identified, which may reveal novel therapeutic targets to enhance the efficacy of radio-immunotherapy in men with prostate cancer.

What this means to patients:  Dr. Aggarwal and team are investigating the potential for therapeutic synergy between various types of radiation therapy and immunotherapy, as well as the mechanisms by which this occurs.  The team is also developing biomarkers and novel PET imaging methods to measure anti-tumor immune responses.  This will enable optimization of radio-immunotherapy as an effective new therapeutic strategy for patients with prostate cancer.