March 23, 2026 —
Researchers at the Cancer Center Clínica Universidad de Navarra (CIMA) have developed an experimental cancer treatment that combines radiotherapy with an AAV-based gene therapy vector, showing strong antitumor activity in preclinical studies. The findings were recently published in the high-impact journal Cancer Cell, and investigators aim to begin the first patient clinical trial in 2027.
Radiotherapy is one of the most widely used treatments for cancer. In addition to directly damaging tumor cells, radiation can stimulate the immune system to recognize and attack cancer. However, tumors often create an immunosuppressive environment that limits this immune activation, preventing durable antitumor responses.
To overcome this challenge, the CIMA research team designed a gene therapy vector based on adeno-associated virus (AAV) that delivers the gene encoding interleukin-12 (IL-12), a potent immune-stimulating cytokine. When injected directly into tumors, the AAV vector enables tumor cells to locally produce IL-12, triggering immune activation in the tumor microenvironment.
According to Dr. Juan Dubrot, principal investigator of the Tumor Evasion and New Targets Group at CIMA and co-director of the study, combining the two approaches significantly enhances therapeutic activity. The researchers observed that intratumoral injection of the AAV gene therapy vector alongside radiation therapy caused the tumor itself to produce IL-12, which in turn activated immune responses capable of attacking cancer cells.
This strategy provides a dual therapeutic mechanism. Radiation therapy directly damages tumor cells while simultaneously creating conditions that enhance immune activation. Meanwhile, the AAV vector drives localized IL-12 production within the tumor, amplifying immune responses while minimizing systemic toxicity. Because the therapeutic protein is produced primarily within the tumor, the approach reduces the risk of inflammatory side effects in other organs.
Preclinical experiments demonstrated encouraging safety and efficacy across multiple solid tumor models, including melanoma, pancreatic cancer, colorectal cancer, and lung cancer. In these models, the combination therapy generated strong antitumor immune responses and improved tumor control compared with either treatment alone.
The research team is now continuing toxicology studies to determine the optimal dosing strategy for the AAV vector therapy. If these studies proceed as expected, investigators plan to initiate a Phase I clinical trial in 2027 to evaluate the safety and therapeutic potential of the approach in patients.
The study involved international collaboration with scientists from Queen Mary University of London and the Broad Institute in Cambridge, and received funding from several public and philanthropic organizations, including Spain’s Ministry of Science, Innovation, and Universities and the Government of Navarre.
By combining radiotherapy with targeted AAV gene therapy, the research highlights a promising strategy for enhancing immune responses against solid tumors—an area where many current immunotherapies still face significant challenges.
