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Novel CAR-T cell therapy established at the University Medical Center Freiburg / Great potential of the therapy expected

At the end of August, doctors at the University Medical Center Freiburg used a new type of gene therapy against cancer for the first time - with great success. The patient suffers from diffuse large cell lymphoma, the most common form of lymph gland cancer, which quickly leads to death if left untreated. As part of a so-called CAR T-cell therapy, the patient's immune cells, the so-called T-lymphocytes, were genetically modified in the laboratory so that they can recognize and fight the cancer cells. Initial examinations after the therapy show that the therapy works very well. Due to its complexity, CAR T-cell therapy can only be carried out in a few clinics that have extensive experience in the transplantation of cell preparations.

"It is incredible to see how much the tumor cells have been pushed back throughout the body - and that only a few weeks after CAR T-cell therapy," says PD Dr. Reinhard Marks, attending senior physician at the Department of Internal Medicine I at the Freiburg University Medical Center.

Despite intensive treatment of her lymph gland tumor, the 44-year-old patient's cancer cells had returned very quickly. "In such a situation, the long-term control of the cancer poses a difficult therapeutic challenge. No more cancer cells were detectable in the patient after the CAR-T cells were used," says Marks. Previous studies suggest that in most cases it is possible to keep the cancer under control for a long time with this good response.

"With CAR-T cells, we are gaining a very effective weapon, especially in the fight against blood cancer. I am convinced that the approach could also be effective for other types of tumor. The first successful application has confirmed our goal of expanding this form of therapy in Freiburg," says Prof. Dr. Justus Duyster, Medical Director of the Department of Internal Medicine I at the Freiburg University Medical Center.

Arming defense cells against cancer

The immune system provides the body with numerous weapons to render cancer cells harmless. Sometimes, however, the immune system does not recognize the malignant cells. In certain cases, the immune system can now be given a helping hand. Doctors take T lymphocytes from the patient. "It is important that sufficient functional T lymphocytes can be obtained from the heavily pre-treated patients in order to produce an effective CAR T cell preparation," says Prof. Dr. Ralph Wäsch, Head of the Cell Therapy Section at the Department of Internal Medicine I at the Freiburg University Medical Center. In the laboratory, the blueprint for an artificial surface receptor is introduced into the T lymphocytes using gene therapy. This new "Chimeric Antigen Receptor", or CAR for short, on the surface of the T-lymphocytes fits like a lock and key to structures on the tumor surface. The modified cells are then transplanted back into the patient, where these CAR T cells are activated and specifically destroy the tumor cells.

The great potential of the therapy is offset by certain risks and side effects. In particular, cell activation can lead to a so-called cytokine storm, in which inflammatory reactions, such as severe fever, are triggered by the release of messenger substances. Furthermore, temporary and completely reversible changes in brain function can occur. This is why comprehensive internal, neurological and intensive medical care is essential during treatment. "This therapy can only be offered if oncology, neurology, intensive care and transplantation medicine work together optimally, as is the case here in Freiburg," says Duyster. To ensure the safety of patients, staff are specially trained in handling these cell preparations.

"So far, CAR T-cell therapy has only been approved in Germany for a few forms of leukemia and lymphoma and may generally only be used in patients who do not respond as desired to standard therapies," says Prof. Dr. Toni Cathomen, Head of the Institute of Transfusion Medicine and Gene Therapy at the Freiburg University Medical Center. As part of a large EU project, a team led by Cathomen is researching ways to make the therapy safer using CAR-T cells that can be switched off. "If we succeed in increasing the safety of the therapy, we could treat significantly more patients with it and use it for other types of cancer," says Cathomen.

Contact: 
Prof. Dr. Justus Duyster
Medical Director
Department of Internal Medicine I
Freiburg University Medical Center
Phone: 0761 270-34060
justus.duyster@uniklinik-freiburg.de