Innovative Radiotheranostic Therapy Under Investigation for Aggressive Bone Cancer
Researchers at the UCLA Health Jonsson Comprehensive Cancer Center are examining a cutting-edge therapeutic strategy that combines imaging and targeted radiation to combat aggressive bone cancer. This approach, known as radiotheranostic therapy, simultaneously detects and targets cancer cells. By integrating imaging with precision radiation delivery, this method aims to improve patient selection and increase targeting accuracy while potentially overcoming cancer resistance mechanisms.
The initial human clinical trial is underway at UCLA, focusing on individuals with metastatic osteosarcoma, a severe bone cancer primarily affecting younger populations. This phase 1 study evaluates whether a radioactive antibody can safely identify and eradicate tumors unresponsive to traditional treatments.
The research is led by Dr. Noah Federman, the Glaser Family Endowed Chair at UCLA, and is supported by foundational discoveries from a team led by Dr. David Ulmert and Dr. Robert Damoiseaux. International collaboration with academic institutions in the U.S. and Europe underpins this initiative. The clinical translation is supported by Lantheus, a company specializing in radiopharmaceuticals.
Outcomes for localized osteosarcoma have improved; however, survival rates for metastatic or recurrent cases have not seen significant advances. The current trial presents an opportunity to explore a more precise therapeutic option than previously available treatments.
A novel monoclonal antibody, DUNP19, has been developed to target LRRC15, a protein overexpressed in several aggressive cancers. This protein is abundant in the fibrous tumor microenvironment, contributing to resistance against immune system attacks. Unlike conventional antibodies, DUNP19 penetrates tumor cells, enhancing its therapeutic delivery.
Paired with lutetium-177, this process enables DUNP19 to act as a dual-function agent, facilitating both diagnostic imaging and targeted radiation therapy. This configuration allows precise tumor targeting while minimizing damage to surrounding tissues.
Previous preclinical studies demonstrated that this LRRC15-targeted therapy effectively retards tumor growth, enhances survival, and remodels the tumor microenvironment to facilitate immune system engagement. Encouraging results were observed in models of osteosarcoma, glioblastoma, aggressive colorectal, and breast cancers.
This exploratory trial at UCLA seeks to determine therapy safety, efficacy, and imaging potential. With promising early results, the strategy may extend to treat other cancers expressing the LRRC15 protein, with assessments in additional multi-center trials already commencing in Australia.