Personalized medicine is widely regarded as a megatrend of the future. Dolores Schendel and her biotech company Medigene go one step further. The company has declared war on cancer with individualized therapies. Gene tests and big data play a key role. An inside look.
From the window of her office,
Dolores Schendel can make out the shape of the Munich Helmholtz Zentrum through the fog. Schendel, CEO of biotech company Medigene, headed the Helmholtz Institute of Molecular Immunology for 16 years. “That’s where it all started,” she says. The scientist and entrepreneur has devoted most of her life to research: she began investigating T cells and their therapeutic potential back in the 1970s, and her work has won multiple awards, including from the German Cancer Aid Foundation.
Schendel is one of the pioneers of the therapies that are changing the face of medicine. Her research is an important step toward medical care that is personalized and – increasingly – even individualized, with precision-targeted therapies based on the genetic, molecular or cellular characteristics of patients. Using these biomarkers, physicians can identify which drugs are best suited for which patients, how effective they are likely to be, and how well patients are likely to tolerate them. With these precision approaches, physicians could avoid needless treatment, ineffective therapies and unnecessary side effects.
The immune system is like a fingerprint. It’s unique to every individual. Since we work with the patient’s living cells, the therapy is precision-targeted to the patient.
Digital transformation is a vital catalyst for this new era of medicine – particularly in cancer therapy, because tumors arise from gene mutations. Through genetic tests, doctors can now identify the cancer-causing mutations. The tests disclose everything about the specific characteristics of the tumor, and explain why some therapies will work for one patient but not for the next. The tests are used in various ways, often involving
big data analytics: results are collected and collated, and then compared with thousands of patient records all over the world. The information is analyzed by algorithms as well as by doctors and bioinformaticians. Doctors then have the best possible basis for treatment decisions. What will give the patient the best chances? Which targeted drugs can be used?
Big data for a strong immune system
Dolores Schendel and Medigene’s 100-plus employees go a step further. The patient’s immune system is modified to target certain cancer cells. Yet to do this, it first has to know the enemy. To provide this knowledge base, Medigene is sifting through the data libraries that store the properties of just about every tumor cell. Breast cancer looks different from liver or lung cancer, prostate cancer or leukemia. What is above all relevant is the cell surface, as this where the antigens are located, critical tumor markers that T cells can target with specific receptors. It’s all about designing the right key for a particular lock – and this is what will take the step from personalized to individualized medicine. “The immune system is like a fingerprint. It’s unique to every individual. Since we work with the patient’s living cells, the therapy is precision-targeted to the patient,” says Schendel.
Schendel, who was born in the USA, has been researching T cells for decades, first in the USA and the UK, and now in Germany. She was Professor of Immunology at the University of Munich, and in 1998 became the first woman to head the Immunology Institute at the
Helmholtz Zentrum. “Research has always been what matters most to me. I wanted to understand everything about T cells, and figure out how to use them in the fight against cancer.”
Whenever we have an infection, the body produces abundant T cells that specifically target pathogens. Once active, T cells mercilessly destroy viruses or bacteria. Once the job is done, they die off, leaving only a small remainder as memory cells in the lymph nodes and bone marrow. These memory cells go on instant high alert should the pathogens reappear. This is why people cannot usually become ill twice from the same pathogen.
Medicines such as Novartis’ Kymriah can help in early stages of the disease (Image: Novartis)
Certain T cells can also fight tumors. “But they have no chance against the sheer numbers of rapidly dividing cancer cells,” says Dolores Schendel. This is where Medigene comes in. T cells are taken from the patient’s blood. Then special receptors are added in the laboratory and the cells are grown over the course of just a few weeks. The T cells are transferred back to the patient, and can then identify antigens on cancer cells.
These receptors are Medigene’s contribution to a medical revolution: probably no other company pursues such a systematic and automated approach to discovering T cell receptors. Medigene uses bioinformatic software that trawls through the huge volumes of information in publicly available databases on protein abundance. Using this data, researchers can zero in on new target structures and search for receptors to combat them. Potential side effects can also be better assessed.
Medigene also relies on big data outside of research – for market analysis, for instance. Before products enter the development pipeline, analytics are used to determine whether there is a sufficiently large market, and how key medical trends and competing products will affect development.
Immunotherapies on the rise
But back to the T cells. “The altered, living cells are returned to the patient via transfusion, and can then take effect in the body,” explains Dolores Schendel. The idea is that the new T cells will detect and destroy cancer cells, ideally also depositing memory cells that will continue to search for cancer cells and prevent a much-feared recurrence.
Medigene currently has three T cell technologies in development: cancer-targeting T cells, a cancer vaccine with dendritic cells for use after chemotherapy, and a platform for developing T cell-specific antibodies. Clinical trials are already underway for the first two approaches. Schendel hopes for positive results; for Medigene this would be a major and very important success.
Although immunotherapies are expensive at the point of use, they are usually needed only once, and may be permanently effective.
Oncology is not the only field of medicine where immunotherapy is on the rise. It’s easy to understand why: ultimately, it is the immune system that decides whether we are ill or healthy. By influencing the immune system, scientists can unlock new possibilities for personalized and individualized therapies. If medical knowledge is then digitally combined with bioinformatic methods, an entirely new vista of opportunity opens up.
“We’re only in the second generation of these therapies. There is still much room for improvement,” says Schendel. The patients currently being treated with T cells in studies have exhausted all other possible treatment options. Yet even with these gravely ill people, some amazing success stories are emerging, mainly in the USA. A case in point is the study on the drug
Kymriah, which is marketed by Novartis: 79 patients were treated, of whom 82 percent were cancer-free after three months. “With CAR-T cells, even advanced cancers can be brought under control,” says Schendel. An important goal will therefore be not just to treat terminally ill patients, but also to use the drugs at much earlier stages of the disease.
Rich vs poor: what price medical care?
The new technologies throw up a range of questions. How will these therapies be funded? Who will protect patient data containing such sensitive information as cell types or genetic fingerprints? Medigene only uses certain characteristics of the human genome, but data protection still plays an important role. All data is encoded, staff are specially trained, and the pseudonymized patient data is stored on secure servers. But if such therapies were to become widely accepted or even standard in the future, medicine and politics would have to completely rethink data protection.
Costs are also a major barrier right now. Despite all the progress, laboratory diagnostics and molecular medicine remain prohibitively expensive; new drugs such as immunotherapy with the active substance ipilimumab cost around 80,000 euros. Cellular therapy, for example with Kymriah, costs around 320,000 euros due to the labor-intensive work in laboratory production. Some experts fear that personalized medicine could therefore be the preserve of an exclusive group of patients, exacerbating the problem of two-class healthcare.
Dolores Schendel disagrees. “We have to keep the big picture in mind. Although immunotherapies are expensive at the point of use, they are usually needed only once, and may be permanently effective. So follow-on costs are lower. We are also eliminating the cost of unnecessary treatment.” Calculation models have in fact shown that personalized therapies work out at lower cost owing to the greater efficiency of treatment. This could reduce the burden both on individual patients and the healthcare system. Cancer patients, in particular, may suffer all their lives not only from the consequences of their illness but also from the after-effects of highly stressful treatment. Many are also unable to return to work.
Cure is a big word. But I am confident we will be able to control the disease.
If a gentle form of treatment with long-term effectiveness were to be found, the cost would probably fall in the long term. Presumably, the growing use of immunotherapy will drive down prices – due to competition between therapies and improvements in production. “If processes were further automated and streamlined, there would be huge potential for savings,” says Schendel. Immunotherapies are both an opportunity and a challenge, but that’s how innovation works.
Meanwhile, the fog outside the office window has cleared. The Helmholtz Institute is now visible. Will cancer be cured in the future? “Cure is a big word. But I am confident we will be able to control the disease,” says Schendel. That is her goal. “I’m still a researcher. But now I’m living the dream of translating knowledge into benefit.“
Lead and sidebar images: Medigene