Scientists from the Center for Applied Medical Research (CIMA) at the University of Navarra have developed a gene therapy technique which improves results in cases of cancer of the colon with metastases in the liver. "Our study confirms that the combination of immune therapy and chemotherapy increases the anti-tumor effect in animal models", explain scientists Jesús Prieto and Rubén Hernández, who are in charge of the project.

Cancer of the colon is very likely to spread to the liver. Over half such patients have hepatic metastases, which severely limit their chances of being cured. In the earliest cases, the metastases can be eliminated by surgery, but in most patients this is not possible, or the metastases reappear in the course of time. In these cases, chemotherapy is the only alternative, but its effectiveness in the long term is limited.

Oxaliplatin is an essential component of the chemotherapy used for cancer of the colon, particularly in patients with liver metastases. However, the disease may recur because of cancerous cells that resist chemotherapy. "For some time now, the anti-tumor effects of interleukine 12 (IL-12) have been under scrutiny. This is a natural stimulator of the immune system, which defends the individual by eliminating the malignant cells. But high doses given intravenously have a toxic effect. In this study, we used a gene therapy vector to achieve IL-12 production within the liver in a sustained and controlled manner".

Clinical application

The research carried out in CIMA at the University of Navarra shows that the combination of IL-12 and oxaliplatin has a greater anti-tumor effect than is obtained by using each one of these separately. According to researchers Prieto and Hernández, "this is because the oxaliplatin not only damages the tumor cells, but actually destroys the immune suppressor cells which are present inside the tumor, thus allowing the IL-12 to be more effective. Moreover, this combined treatment eliminates pre-existing metastases and protects the liver from possible recurrence of the disease. The results we have got in animals suggest that this is a highly promising treatment which could be effective in patients with liver metastases of colon cancer".

At present, the researchers' work is focusing on perfecting the mechanisms for producing gene therapy vectors which are pure and effective enough to use in clinical practice. "At the same time, we are going to validate these results in other experimental models, to try to predict as far as possible the effect that they would have when used in human beings".