UCLA Scientists Develop Novel ‘Radiotheranostic’ Cancer Therapy

UCLA researchers, working with international collaborators, have developed a promising new treatment that can detect, kill, and reprogram some of the most aggressive and treatment-resistant tumors, including osteosarcomas and glioblastomas.

The approach, described in Signal Transduction and Targeted Therapy, uses a specially engineered antibody called DUNP19 to target a protein known as LRRC15, found on the surface of aggressive cancer cells and surrounding stroma. When paired with radioactive particles, the antibody can both illuminate tumors for precise imaging and deliver targeted radiation directly to malignant tissue, while sparing healthy cells.

“Pairing the antibody with radiation creates a powerful ‘radiotheranostic’ approach,” said Dr. David Ulmert, associate professor of molecular and medical pharmacology at UCLA. “This two-pronged strategy allows exquisite control over radiation’s strength—mild for scanning, intense for killing—resulting in fewer side effects than standard treatments while reprogramming the tumor’s immune-resistant environment.”

Osteosarcomas and glioblastomas are frequently resistant to chemotherapy and immunotherapy, in part because of LRRC15, which helps tumors grow and evade immune responses. Since LRRC15 is largely absent from healthy tissue, it makes an ideal target for therapies like DUNP19.

When paired with the radioactive isotope Lutetium-177, DUNP19 acts like a guided missile, delivering toxic payloads directly to tumor and stromal cells. Beyond tumor killing, the therapy dismantles LRRC15-producing stromal cells that shield cancer from immune attack, enabling infiltration by T cells and natural killer cells.

In models of osteosarcoma, glioblastoma, triple-negative breast cancer, and colorectal cancer, DUNP19 carrying radioactive particles either cured tumors, slowed growth, or extended survival. In osteosarcoma bone models, nearly all treated mice showed no signs of disease, while untreated ones succumbed.

Ulmert noted, “This therapy breaks down that shield, reprograms the environment, and makes other treatments more effective. This new radiotheranostic approach shows promise by halting cancer growth, extending survival with minimal side effects, and enhancing immunotherapy—potentially aiding more patients where existing treatments fall short.”

A UCLA-led clinical trial led by Dr. Noah Federman is now being prepared to test the therapy in patients with metastatic osteosarcoma, with enrollment expected later this year.