Pioneering CAR-T cell therapy for blood cancers

In CAR T-cell therapy, an artificial molecule called „CAR“ („chimeric antigen receptor“) is incorporated into special defence cells of the immune system, the T-cells, which guides these cells like a navigation system to certain surface features of tumour cells. In the patient's body, they can thus detect and kill the diseased cells with astonishing effectiveness. CAR-T cells are living cells that can no longer be directly controlled in their activity after transfer to the patient. This can be particularly problematic if side effects occur.

A team led by Prof Michael Bachmann, Director at the Institute for Radiopharmaceutical Cancer Research at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR), has therefore developed a new drug in close collaboration with the Dresden University Medicine to develop the UniCAR technology, which is based on CAR T-cell therapy and is one of the most promising approaches to immunotherapy. The researchers have incorporated an additional switch that enables direct therapy control in the patient's body.

The modified CAR-T cell now does not bind directly to the tumour cell. Instead, a special link - a target module - is interposed between the immune cell and the cancer cell, which makes it possible to kill the cancer cell in the first place. As the artificially generated target modules are quickly excreted from the body, the activity of the UniCAR-T cells can be controlled and thus side effects better controlled.

A research team led by biologist Dr Claudia Arndt from the HZDR Institute of Radiopharmaceutical Cancer Research and physician Dr Frederick Faßlrinner from the Dresden University Medical Centre is using a module that targets a tumour-associated surface molecule of AML called FLT3. FLT3 is a type of marker that helps to better recognise cancer cells. The researchers succeeded in killing AML cell lines as well as primary samples from AML patients in vitro with high efficiency. The team was also able to confirm this in animal models. Analyses using positron emission tomography also indicate that the UniCAR-T cells can be switched on and off quickly, making it possible to control the therapy rapidly.

In order to be able to successfully treat AML with immunotherapy, it is crucial to prevent resistance to therapy and depletion of the T cells. UniCAR technology could achieve this, as Frederick Faßlrinner emphasises: „The combination of different target molecules makes it possible to attack the AML cells via different target structures. This means that the cancer cell has less chance of evading the therapy. We hope to be able to cure more patients this way.

The researchers are confident that breaks between individual applications will give the UniCAR-T cells time to recover to prevent exhaustion.

„Overall, the presented preclinical data encourage the further development and clinical implementation of FLT3-specific UniCAR-T cells for the treatment of AML“, concludes Claudia Arndt. „This applies in particular in combination with the so-called CD123-targeted UniCAR-T cell therapy, which is currently being trialled in patients in a first phase I study.“

Arndt and Faßlrinner are working with their team at the Dresdner Mildred-Scheel-Nachwuchszentrum (MSNZ) on CAR-T cell therapy for blood cancers. The MSNZ offers young scientists individual career paths in cancer research. Medical and scientific expertise flow together in so-called tandems. This enables clinically relevant questions to be answered in a joint research team.

Press release of the "HZDR" from 14 September 2023