Radiotheranostic Therapy Shows Promise in Aggressive Bone Cancer Treatment
Investigators at the UCLA Health Jonsson Comprehensive Cancer Center are pioneering a new treatment strategy, radiotheranostic therapy, that simultaneously detects and attacks cancer. This approach, currently undergoing a first-in-human clinical trial, offers a potential breakthrough for patients with metastatic osteosarcoma, a rare and aggressive bone cancer primarily affecting children, adolescents, and young adults.
What is Radiotheranostic Therapy?
Radiotheranostic therapy combines imaging and therapy into a single targeted approach. It first “lights up” tumors at the molecular level, allowing for precise visualization, and then delivers targeted radiation directly to the cancer cells. This dual-purpose method aims to improve patient selection for targeted radiation and overcome the resistance cancers often develop against conventional therapies.
Targeting LRRC15 in Osteosarcoma
The clinical trial focuses on a specially engineered monoclonal antibody, DUNP19, developed at UCLA. This antibody binds tightly to LRRC15, a protein activated by the growth factor TGFβ, which is crucial for tumor growth, spread, and resistance to immunotherapy. LRRC15 is largely absent in healthy tissues but abundant in the fibrous compartment of aggressive cancers like osteosarcoma and glioblastoma. DUNP19 is rapidly absorbed by tumor cells, enabling it to deliver its payload from within.
How Does the Therapy Work?
DUNP19 is paired with the radioactive isotope lutetium-177, transforming it into a “guided missile” that both images and destroys cancer cells and the stromal cells that shield them. By delivering targeted radiation, the therapy ablates LRRC15-expressing cells whereas minimizing damage to surrounding healthy tissue. The ability to use the same molecule for both imaging and treatment allows for exceptional precision, confirming the drug’s location and ensuring it’s hitting the tumor.
Promising Preclinical Results
Years of preclinical research have demonstrated the effectiveness of this approach. In cellular and mouse models of osteosarcoma, glioblastoma, triple-negative breast cancer, and aggressive colorectal cancer, the LRRC15-targeted radionuclide therapy slowed tumor growth, extended survival, and altered the tumor microenvironment to enhance immune response.
Studies published in Signal Transduction and Targeted Therapy showed that nearly all treated mice with osteosarcoma exhibited no signs of disease after therapy. In models of metastatic disease, tumor growth stopped. The therapy dismantled the tumor’s immune defenses by eliminating LRRC15-producing stromal cells, allowing immune cells to infiltrate tumors and shifting gene activity toward immune activation.
Phase 1 Clinical Trial at UCLA
The newly opened phase 1 clinical trial at UCLA is enrolling patients with metastatic osteosarcoma to evaluate the safety, imaging capability, and early signs of effectiveness of the LRRC15-targeted radiotheranostic therapy. Participants will undergo diagnostic imaging to confirm the presence of LRRC15-producing tumors before receiving treatment with the therapeutic radioactive antibody.
Expanding the Potential
Researchers are optimistic about the applicability of DUNP19 to various cancers, including pancreatic cancer and glioblastoma. A multi-center trial assessing the targeting of LRRC15 in a range of aggressive cancers has also opened in Australia.
“This trial is an essential first step,” said Dr. Noah Federman. “Our primary goal is to ensure safety and understand how the therapy behaves in patients, while also looking for early signals that it can support control this devastating disease.”
To learn more about this clinical trial, visit ClinicalTrials.gov.