CAR T-cell therapy: opportunities and risks for cancer patients revealed!

CAR T-cell therapy: opportunities and risks for cancer patients revealed!

FAU has a new expert in the field of CAR T-cell therapy: Prof. Dr. Fabian Müller, who holds the W3 professorship for this promising research area. The Friedrich-Alexander University Erlangen-Nuremberg (FAU) is one of the 15 largest and most research-intensive universities in Germany. It employs over 6,000 people and offers more than 270 study programs for more than 39,000 students. Prof. Müller brings extensive experience from his previous post-doctoral position at the National Cancer Institute in Bethesda, MD, USA.

The research focus of Prof. Dr. Müller focuses on antibody-based therapies that aim to specifically switch off degenerated or dysregulated cells. These technologies are expected to significantly reduce the side effects of traditional cancer therapies, making them a promising approach to fighting cancer.

CAR T-cell therapy and how it works

CAR T-cell therapy is a modern method of treating certain blood and lymphatic cancers, such as acute lymphocytic leukemia (ALL) and non-Hodgkin lymphoma (NHL). The term “CAR” stands for chimeric antigen receptor, which is integrated into T cells to specifically kill tumor cells. The therapy process includes several steps:

• Blutentnahme und Filtration der weißen Blutzellen durch Leukapherese.
• Isolierung der T-Zellen im Labor und deren gentechnische Veränderung zur Herstellung des CAR.
• Verabreichung einer Chemotherapie zur Hemmung von Tumorzellen und Immunsystem (Lymphodepletion).
• Infusion der CAR-T-Zellen, die im Körper aktiv werden.

Each patient receives individual, genetically modified T cells. Two CAR T-cell therapies are approved in Germany: axicabtagene ciloleucel and tisagenlecleucel, both of which target the surface marker CD19. The therapy has proven effective, with studies showing that tumors can shrink significantly.

Side effects and new findings

However, possible side effects should be taken into account. These include cytokine release syndrome, neurological problems such as headaches and dizziness, and cytopenias with low cell levels in the blood. There is also an increased risk of infections. Long-term support and monitoring of patients is planned for up to 15 years after therapy.

A current research team at the University Hospital Düsseldorf (UKD) has intensively studied the side effects of CAR T-cell therapy. Rare cases of secondary cancers, such as T-cell lymphomas, have been observed. Mutations in hematopoietic stem cells have been identified as a possible cause of these diseases. These mutations can arise spontaneously or be promoted by previous therapies such as chemotherapy.

Research has indicated that a patient suffering from primary central nervous system lymphoma developed peripheral T-cell lymphoma six weeks after CAR T-cell therapy, which ultimately led to the patient's death. DNA analysis revealed mutations in the DNMT3A and TET2 genes, which are associated with hematological cancers.

In summary, CAR T-cell therapy represents an innovative treatment option for cancer patients, but also carries certain risks. Ongoing research will be crucial to better understand these risks and, if necessary, to find appropriate pre-therapy screening methods to advise patients individually and minimize the risk of complications.

For further information about CAR T-cell therapy and the associated challenges, we refer to the detailed reports from FAU, German Cancer Society as well as the latest findings from Düsseldorf University Hospital.