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Stefanie Winkler

Interview Targeted Antibody Therapy Against Brain Tumor Glioblastoma

Prof. Reinhard Zeidler about hope in the fight against glioblastoma, the most common and malignant form of brain tumor and how he accelerates the development of antibodies into application.

Prof. Reinhard Zeidler about hope in the fight against glioblastoma, the most common and malignant form of brain tumor and how he accelerates the development of antibodies into application.

"Hope in the fight against glioblastoma, the most common and malignant form of brain tumor: A combination of a highly specific antibody with a therapeutically effective radionuclide* could target metastases."
Prof. Reinhard Zeidler, Head of the Research Group "Therapeutic Antibodies" at Helmholtz Munich


Currently, a specific tumor therapy against so-called glioblastomas is being tested in a clinical phase I trial. The team around Prof. Reinhard Zeidler has not only conducted basic research, but has also scientifically accompanied the entire process up to this point.

What makes this therapy so special?

RZ: We have developed an antibody* that targets glioblastoma cells, specifically binds to them and helps to destroy them. While at the same time sparing healthy brain cells. If the clinical trials are successful, people with glioblastoma could survive longer, because currently applying the standard therapy the median survival from diagnosis is only 12-15 months.

Expert Knowledge: How Does the Helmholtz Munich Antibody Combined with Radionuclide* Work?

The antibody binds specifically to the enzyme carbonic anhydrase XII, which is exclusively found in the brain on the surface of cancer cells – presumably because it is important for their rapid growth. Coupled to lutetium-177, a radioactive emitter (radionuclide), the antibody is injected into the resulting cavity after surgical removal of the main tumor, from where it migrates into the surrounding brain tissue and binds to remaining tumor cells. The antibody has a dual effect: First, it inhibits the enzyme, and second, it specifically directs lutetium-177 to tumor cells that could not be eliminated by standard therapy. The radiation released during the radioactive decay of lutetium-177 destroys the tumor cells in the immediate vicinity. These scattered tumor cells are often the reason for the recurrence of the disease, which is referred to as relapse. The new therapy is expected to significantly delay the occurrence of recurrences.

Why Are People With Glioblastoma Currently Having Such a Short Survival Time?

RZ: Starting from the main tumor, many individual cancer cells spread into the healthy brain tissue. These cancer cells are not destroyed efficiently enough with the standard therapy, usually consisting of a combination of radiation and chemotherapy, which has been used until now after surgical removal of the tumor. As a result, individual surviving cancer cells begin to divide and form a new tumor, often leading to death – despite successful removal of the main tumor. Glioblastomas are very aggressive and malignant brain tumors: They spread particularly strongly and form recurrences quickly. To improve the prognosis of those affected, these individual tumor cells and recurrences must be combated more efficiently. I have hope that we will succeed in this with our antibody.

Why does the antibody therapy work better?

RZ: Our antibody is administered locally and acts on the spot, so to speak. There, it specifically docks onto tumor cells, and the coupled radionuclide efficiently destroys them through therapeutically effective radioactive radiation. Chemotherapy is far less specific – resulting in, on the one hand, scattered cancer cells, that are not destroyed as efficiently and, on the other, more severe side effects due to healthy tissue damage.

Hope in Targeted Antibody Therapy

What are your expectations for the antibody?

RZ: We know so far that treatment with the antibody is very well tolerated. Whether it also leads to longer survival will be investigated in an extensive clinical trial. Even though I see great potential in our antibody, it will probably not be a miracle cure in the fight against glioblastomas. What I do hope for, however, is an improvement in the quality of life and a significantly longer survival for those affected.

What catalyzed the way to this promising cancer therapy?

Particularly important to me is the freedom to implement unconventional ideas and to work on projects that seem risky and are not 'mainstream'. I was able to do this at Helmholtz Munich and at the LMU Hospital. The immediate proximity to the Klinikum Großhadern and to the Helmholtz Munich Core Facility "Monoclonal Antibodies", which was formerly headed by Dr. Elisabeth Kremmer and located in our building in Großhadern, were and are further important success factors. In addition to the appropriate infrastructure, short distances, personal contacts to physicians and cooperation partners, and access to patient material are essential for our work. The most important catalyst, however, was probably that I believed in the special technology with which we produce our antibodies from the very beginning, and still do. With it, we have developed many therapeutically promising antibodies and gained new insights into cancer cells.

What Does the Core Facility “Monoclonal Antibodies” Do?

What happened after you have developed this Antibody?

You can only develop a therapeutic antibody in a team. I would like to single out Dr. Franz Gildehaus from the Institute of Nuclear Medicine and especially Prof. Hans-Jürgen Reulen, the former head of the Department of Neurosurgery at the LMU Hospital. Specialized departments of Helmholtz Munich supported the technology transfer internally, and Ascenion GmbH, the members of my working group and many cooperation partners also contributed greatly to the success. Realistically, we would still have failed with our academic team if the company ITM Isotope Technologies Munich had not supported the project and licensed the antibody: they were instrumental in the approval process for the antibody in the last step.

Developing an antibody that is suitable for the treatment of glioblastomas is, of course, a great success for me personally! But it is also proof that the technology of how we produce many different antibodies and identify the most promising ones has great potential: The antibody for the treatment of glioblastoma is just the first in this series. I am very confident that more antibodies will be suitable for treating other types of cancer. But in order to know that, a lot of money and work still needs to be invested.

Helmholtz Munich Promotes Translational Research

For this purpose, you have founded the spin-off “Eximmium”…

The development of therapeutic antibodies is a long and expensive process. It cannot be done with public funds alone. That's why we founded our spin-off 'Eximmium', which has exclusively licensed many of these antibodies from Helmholtz Munich. This is the only way we have the chance to identify financially strong investors who ideally have not only money but also a network and important know-how to bring further antibodies into the clinic in the foreseeable future. Here, I see Eximmium on a very good path.

Find Out More About Prof. Reinhard Zeidler and Connected Research

Prof. Reinhard Zeidler, Head of the Research Group "Therapeutic Antibodies" at the Institute of Structural Biology at Helmholtz Munich and at the Clinical Center of Ludwig-Maximilians-University Munich (LMU).