New approaches to cancer, allergies and other diseases
The Immunotherapy are a relatively new approach to treatment based on targeted activation of the immune system. For example, cancer cells are to be fought with the support of the body's own defenses. Professor Dr. med. Dirk Schadendorf, Director of the Clinic for Dermatology, Venereology and Allergology at the University Hospital Essen and Director of the West German Tumor Center (WTZ), answered the most important questions about immunotherapy.
How does antibody-assisted treatment work?
Activating the immune system against cancer cells has been promising for years. So-called "checkpoint inhibitors" ensure that the body's own immune cells fight cancer. The drugs do not attack the cancer cells themselves, but intervene in the control of the immune response, so-called checkpoints. A series of studies is now showing how successfully the immune system fights cancer cells once the right shift levers are actuated by special antibodies from the laboratory: deadly tumors shrink rapidly, some disappear completely. Patients with advanced cancer and poor prognosis survive much longer than with any other therapy.
Cancers that are difficult to treat become vulnerable to immunotherapy: oncologists are currently seeing the greatest success in black skin and lung cancer. Especially in malignant melanoma, immunotherapies are a pioneering treatment pillar, since this form of cancer is almost resistant to chemotherapeutic agents. The cancer can no longer hide from the immune cells. While chemotherapy attacks the tumor directly with cell toxins, the antibodies activate immune system defense cells. You can no longer be fooled by cancer. The advantage: your own immune system can recognize tumor-specific changes very well. For example, immunotherapy does not only respond well to black skin cancer, but also to other tumor diseases that are triggered by so-called carcinogens, i.e. cancer-causing substances or radiation such as alcohol and cigarette consumption or UV light. These include, for example, tumors of the lungs, bladder or kidney and in the head and neck area. Even with these types of cancer, external influences damage the genetic material in the cells and lead to tumor development.
What distinguishes immunotherapy from previous treatment approaches?
Immunotherapies show good treatment success for black skin cancer: In 2012, the first immunotherapeutic drug in Europe was approved for this type of cancer. Further so-called "checkpoint inhibitors" followed in 2015. Thus, immunotherapies for numerous cancers are becoming increasingly important. The form of therapy continues to play a pioneering role in the treatment of black skin cancer. Because the new drugs enable for the first time that up to 50 percent of those affected respond to the therapy of malignant melanoma. This has a dramatic impact on average survival rates. Just ten years ago, just under every 20 patients survived the following five years and longer as soon as the black skin cancer had metastasized. Nowadays, the five-year survival rate is 40 to 45 percent - almost every second. A significant improvement has occurred for a significant proportion of the patients.
The special thing about immunotherapies: If the patient responds to the treatment and the tumor shrinks, this therapeutic benefit often lasts for years. This is a new quality in cancer therapy. Because chemotherapy can also shrink numerous tumors, success usually does not last that long. The immunotherapies are characterized by the fact that they do not directly destroy the cancer cells. Instead, the drugs enable the body's immune system to keep the tumor under control.
But even with inflammatory skin diseases such as psoriasis and neurodermatitis, immunotherapies are currently experiencing enormous tailwinds. There is now more than ten different antibody therapies for psoriasis, all of which have the goal of changing the effectiveness of the immune system and fighting inflammation on the skin and internal organs. Psoriasis patients often have not only the visible inflammation of the skin. Vessels are also often affected; changes in the brain and heart lead to an increased risk of a heart attack or stroke. Initial study results suggest that the antibodies used in psoriasis may also be of benefit there.
With which diseases is an application possible?
Immunotherapy often works wonders for skin and lung cancer. However, the therapy does not always work. But when it does, the cancer is often checked for a long time. The first years of use have shown that a large proportion of patients respond to it and, above all, benefit in the long term and for years.
Numerous other applications are currently in clinical trials. Cancer immunotherapy promises new hope, for example, for Merkel cell carcinoma, a rare but particularly aggressive skin cancer. The checkpoint inhibitor avelumab has also been on the market for therapy in Germany since autumn 2017. For advanced squamous cell carcinoma, a rare form of white skin cancer that spreads to the lymph nodes and organs, approval of a new checkpoint inhibitor is expected in early 2019. However, immunotherapy has also found its way into lung, bladder, head and neck cancer and kidney cancer in recent years and has established a new treatment pillar.
What potential do you see for the future?
Many patients already benefit from vastly improved treatment options. Even if the annual therapy costs for the new drugs initially appear to be relatively expensive in comparison to old forms of therapy, the great benefit for those affected quickly becomes apparent. For the first time, the new antibodies in psoriasis give us the possibility that more than 90 percent of people's skin heals again. With older forms of therapy, on the other hand, the healing rates of the skin were at best 50 to 75 percent, which are determined using the so-called PASI Score (Psoriasis Area Severity Index), a psoriasis index. According to initial studies, around seven out of ten patients respond to antibody therapy. The first drug for neurodermatitis is now approved in Germany. We see a significant improvement, particularly in the case of severe illnesses.
But how long does the therapy with the new drugs have to take? When is the right time to stop taking it so that people with chronic diseases such as neurodermatitis or psoriasis can also be temporarily therapy-free? It is particularly important here that those affected rely on expert expertise. Current research is also increasingly focusing on these questions and examining the long-term consequences of immunotherapy.
Which antibodies have already been tested?
The dermatological clinic of the Essen University Hospital is one of the leading research centers for immunotherapy for inflammatory skin diseases and all forms of skin cancer. This also includes a wide range of courses. Currently, many study concepts are based on the good experience in treating all forms of skin cancer with so-called PD-1 antibodies. Antibody therapy came to the German market for the first time in 2011 with ipilimumab. The active ingredient triggers an increased immune response and is used in advanced melanoma. Other drugs are about to be approved here. A special research focus is also the combination of immunotherapies with other treatment approaches. A study in which the lung carcinoma was first irradiated and then the checkpoint inhibitor durvalumab was used was particularly promising. The results suggest that patients in the advanced stage survive significantly longer, which recently led to the approval of the PD-1L inhibitor durvalumab in lung cancer. The use of antibodies is currently being tested at a breathtaking pace. The PD-1 antibodies are in clinical trials for more than 30 types of tumor.
One of the most important fields in the future will also be the combined therapy of effective, targeted drugs with checkpoint blockers. Expectations are particularly high in patients with black skin cancer and a so-called BRAF mutation, which occurs in 40 percent of those affected. The hope is that even in the case of inoperable or metastatic melanoma, up to 85 percent of the affected patients will respond to the tumor therapy and benefit from the therapy in the long term, thereby further increasing survival rates.
What are the risks?
The antibody therapies trigger an increased immune response and thus act at the point of contact between the tumor and T cells. The activation of the immune system fights the cancer cells, but it can also target healthy cells in the body, so that sometimes serious and even life-threatening autoimmune diseases of the intestine, thyroid or other organs can occur. Overall, however, therapy with PD-1 antibodies is very well tolerated. There are very few cases where treatment is stopped due to serious side effects. As with all new drugs, the risks and possible benefits of immunotherapy must also be weighed up, as no reliable long-term data have yet been collected. But with response rates of up to 40 percent - especially in melanoma patients in the advanced tumor stage and people with inoperable, metastatic and aggressive forms of cancer - immunotherapies are a great hope only for short-term improvement.
About the interview partner:
Professor Dr. Dirk Schadendorf is director of the Clinic for Dermatology, Venereology and Allergology at the University Hospital Essen and director of the West German Tumor Center (WTZ), the largest tumor center in Germany and one of the leading oncological centers of the German Cancer Aid. He is also chair of the Dermatological Oncology Working Group and is currently involved in more than 30 clinical studies. For his studies on black skin cancer, Prof. Schadendorf received i.a. 2010 the German Cancer Award in the "Clinical Section". One of his main research areas is white and black skin cancer. Prof. Dr. In 2017, Dirk Schadendorf took first place in the ranking of the laboratory journal, one of the most renowned scientific magazines, as the most cited cancer researcher in Germany - with more than 17,000 citations. One piece of work is particularly outstanding in which the BRAF kinase inhibitor vemurafenib was tested on patients with melanoma in a phase 3 clinical study. A certain mutation in the BRAF gene had previously been detected in their degenerate cells. (fp)
Author and source information
This text corresponds to the specifications of the medical literature, medical guidelines and current studies and has been checked by medical doctors.
Dipl. Geogr. Fabian Peters, Barbara Schindewolf-Lensch
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