Cancer vaccine study
in tumor diseases with DNAJB1-PRKACA gene fusions

FL-HCC is a rare tumor disease that typically affects people without a history of underlying liver disease. In recent years, an increasing incidence of these tumors has been observed. The 5-year survival rate for patients with FL-HCC is currently only 45%. This is mainly due to the fact that the removal of the tumor by surgery is currently the only treatment option that can achieve a cure. However, surgery can only be performed meaningfully if the cancer is diagnosed before metastases (spread of tumor cells to other organs) occur, and even after successful surgery, the disease may relapse. If metastases have already occurred, the only possibility is a targeted, so-called systemic therapy that reaches all tumor cells in the body, e.g. in the form of chemotherapy. However, according to current knowledge, FL-HCC rarely responds to chemotherapy or other systemic therapies in the long term, so there is currently no standard treatment for advanced FL-HCC. This makes the development of new treatment options, particularly to prevent relapses after initial therapy, an urgent necessity.

For many years, vaccinations have been used to prevent infectious diseases such as measles, mumps and influenza. The principle of these vaccinations is that parts of pathogens (also called antigens) are administered to the patient. This activates the immune system, enabling it to recognize and fight off any subsequent contact with these pathogens. Today, it is assumed that a new type of vaccination can also be used to treat tumors. In contrast to infectious diseases, where vaccination is used as a preventive measure, these cancer or tumor vaccines are used in patients who already have cancer, which is referred to as therapeutic cancer vaccination. An attractive target for such a therapeutic cancer vaccination in advanced tumor diseases is a specific genetic recognition feature of the tumor. This feature can be used as a target structure to direct the immune system against the tumor with a therapeutic cancer vaccination.

In current studies of tumor tissue from patients with fibrolamellar hepatocellular carcinoma, the so-called DNAJB1-PRKACA gene fusion could be identified as a genetic hallmark of the tumor. A fusion transcript is a “combined” protein that is formed based on the fusion of two different genes and is largely responsible for tumor development. The DNAJB1-PRKACA gene fusion is present in FL-HCC as a trigger of tumor development, but there are also isolated cases of other tumor diseases, e.g. of the pancreas or bile ducts, in which the DNAJB1-PRKACA fusion transcript is detected.

The therapeutic cancer vaccine Fusion-VAC-XS15 administered in this study contains a peptide (protein) derived from this DNAJB1-PRKACA gene fusion. In order for the therapeutic cancer vaccine to trigger an immune response against the tumor, an immunostimulator, a so-called adjuvant, must be used in addition to the vaccination peptide. In this study, the adjuvant XS15 is used, which is injected under the skin together with the vaccination peptide and the emulsifier Montanide. XS15 is used to activate immune cells at the vaccination site, thus enabling a strong immune response. The results of initial studies on the use of XS15 in humans are promising in terms of the tolerability and effectiveness of the immunostimulator. Preliminary results from four ongoing studies with peptide vaccines containing XS15 show that vaccination was able to stimulate a good and strong immune response, especially of the so-called T cells against the respective vaccine peptides used.