Scientists at the research center Applied Medicine (CIMA ) of the University of Navarra have developed a gene therapy technique that improves results in colon cancer with liver metastases. "Our study confirms that the combination of immunotherapy and chemotherapy increases the antitumor effect in animal models," explain Drs. Jesús Prieto and Rubén Hernández, responsible for work.

Colon cancer has a very marked tendency to spread to the liver. In particular, more than half of the patients have liver metastases, which severely limit their chances of cure. In very early cases the metastases can be removed by surgery, but in most patients this is not possible, or the metastases reappear after some time. In these cases chemotherapy is the only alternative, although its long-term efficacy deadline is limited.

Oxaliplatin is an essential component of chemotherapy used in colon cancer, particularly in patients with liver metastases. However, there is a possibility of disease recurrence, due to cancer cells that resist chemotherapy. "The antitumor effects of interleukin 12 (IL-12), a natural stimulator of the immune system, which defends the individual by eliminating malignant cells, have long been investigated. However, high doses administered intravenously are toxic. In this work we have used a gene therapy vector to achieve the production of IL-12 within the liver itself in a sustained and controlled manner."

Clinical application

The study carried out at CIMA of the University of Navarra shows that the combination of IL-12 plus oxaliplatin exerts a greater antitumor effect than that obtained with these molecules separately. According to Drs. Prieto and Hernández, "this is because oxaliplatin not only damages the tumor cells but also destroys the immune suppressor cells that are present inside the tumor, thus allowing IL-12 to have a greater effect. In addition, this combination treatment eliminates pre-existing metastases and protects the liver against possible recurrences. The results obtained in animal models confirm that this is an extremely promising therapeutic modality that could be effective in patients with colon tumors metastatic to the liver."

Currently, the researchers' work is focused on refining the mechanisms to produce gene therapy vectors with performance and purity compatible with clinical use. "At the same time, we intend to validate these results in other experimental models to predict as far as possible the effect in humans."