Researchers at Cima University of Navarra have developed a new immunotherapy combination that improves efficacy in animal models of hepatocarcinoma. This is a concept test that sets the groundwork instructions for the application of this treatment in patients with the most common liver cancer.

In recent years the fees survival rates of patients with liver cancer have increased markedly. However, further progress is needed to improve its efficacy and to discover biomarkers that predict response to treatment. "One of the main objectives in the research of this disease is to have reliable and clinically useful animal models to study new therapies. In this work, at partnership with the group of Dr. Amaia Lujambio, from Mount Sinai Hospital in New York, we have developed a mouse model by transferring Genetics from the liver with which we have been able to test new combinations of immunotherapy", explains Dr. Ignacio Melero, co-director of the Immunology and Immunotherapy Program at Cima University of Navarra, integrated in the Cancer Center Clínica Universidad de Navarra, and director of the work.

The experimental study has shown that the immunotherapies currently applied in patients have a partial effect on this new animal model . However, their efficacy increases with synergistic combinations of other agents, such as anti-CD137 antibodies, interleukin 2 or with adoptive cell therapy. "These joint administrations substantially increase the therapeutic result . In addition, through advanced confocal microscopy, we have been able to study the antitumor immune response that occurs in liver samples," says Dr. Carmen Ochoa, researcher at Cima University of Navarra and first author of work. The results have been published in the scientific journal Cell Reports Medicine.

Treatment in patients

"Seven years ago, our group de la Clínica Universidad de Navarra pioneered the application of immunotherapy for the treatment of liver cancer. This subject therapy has radically transformed the course of the disease in many patients. Our challenge is to delve deeper into the mechanisms involved and demonstrate the efficacy and safety of these new treatment combinations in clinical trials with patients," adds Dr. Melero.

The study was conducted at framework of the CIBER de Cáncer (CIBERONC) and the CIBER de Enfermedades Hepáticas y Digestivas (CIBEREHD) and was supported by public and private funding from association Española contra el Cáncer, the Mark Foundation and the Fero Foundation.

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→ Cell Reports Medicine. Synergistic effects of combined immunotherapy strategies in a model of multifocal hepatocellular carcinoma.