According to the statistics, approximately 1,500 people develop a malignant melanoma (skin cancer) every year in Austria, although the actual number is probably much higher. Since the malignant disease tends to metastasise at an early stage, the prognosis is not good and melanoma has long been considered to be hard to treat. However, the use of immunotherapy has brought about a paradigms shift.
Activating the body’s self-defences
The underlying principle of immunotherapy is to activate the patient's own immune system and direct it against cancer cells. An important role in this process is played by so-called immune checkpoints. These are receptor proteins that are formed on the surface of T cells (white blood cells used for immune defence). If specific signalling substances (ligands) bind to the checkpoints, the T cell is curbed. It is this mechanism that naturally regulates the immune system and prevents it from "overshooting" and attacking healthy body cells.
However, cancer cells can also form ligands, which inhibit the immune system via the checkpoints. If the checkpoints of the T cell can be successfully blocked and the ligands thereby prevented from binding to the receptor, the signalling pathway is blocked, the T cell activated, an immune response triggered and the tumour attacked. This blockade is achieved by using so-called checkpoint inhibitors, that is to say artificially manufactured antibodies (humanised monoclonal antibodies), which are administered by infusion.
New: in routine clinical use
Following a three-year trial, MedUni Vienna and Vienna General Hospital now routinely use the new generation of checkpoint inhibitors (Nivolumab and Pembrolizumab, both PD1 antibodies). Hubert Pehamberger, Director of the University Department of Dermatology at MedUni Vienna and Vienna General Hospital and member of the Comprehensive Cancer Center (CCC) says: "For nearly ten years now, our department has been involved in all major studies in the field of immunotherapy." Christoph Höller, melanoma specialist at the University Department of Dermatology, adds: "The results were so successful that we have been using both antibodies as a first-line therapy for about two months now. Complete regression of the tumour is achieved in between 7 – 9% of all patients and, in many others, we are at least able to bring about lasting remission. That is significant, given the essentially poor prognosis of the disease."
Studies investigate new treatment protocols
Inspired by the successes achieved so far, MedUni scientists are now working on further improvements to this therapy. Höller: "We are continuing to conduct studies into immunotherapy. On the one hand, we are testing the combination of checkpoint inhibitors PD1 ( Nivolumab) and CTLA4 (Ipilimumab). On the other, we are starting a study, in which a PD1 antibody is combined with a genetically modified herpes virus." The virus is injected into the metastases and causes the cancer cells to disintegrate. The cancer cell fragments provoke a strong local immune reaction, which is further strengthened by administration of the antibody. Höller: "However, we are also looking at the metastasis of malignant melanomas. Following surgical removal of the skin cancer, there is a risk of metastases forming. Therefore, in an ongoing study, we are administering PD1 antibodies on a quasi-preventive basis and, to put it bluntly, waiting to see that no metastasis occurs."
European Congress of Immunology in Vienna
Immunotherapy in oncology is an important topic at the European Congress of Immunology, taking place in Vienna between 6 – 9 September. MedUni Vienna and the CCC are prominently represented by Christoph Zielinski, Director of the University Department of Internal Medicine I of MedUni Vienna and Vienna General Hospital and Chairman of the CCC, amongst others. Zielinski will chair the session on "Immunotherapy in oncology".