New method for labeling T cells in immunotherapy

Tracking immune cells inside the body

An interdisciplinary team at TUM and the TUM University Hospital has now proposed a solution. In simplified terms, a second artificial receptor is inserted into the modified immune cells. These cells can then be visualized using PET imaging and a specially developed, non-toxic radioactive contrast agent. When this so-called radioligand is injected into the body, it binds exclusively to the modified cells and their descendants, making them visible.

The technique relies on artificial proteins with specific binding properties, known as anticalins. These have been developed since the 1990s by Arne Skerra, Professor of Biological Chemistry at TUM and a pioneer in protein engineering. His work led to the creation of an anticalin that binds the ligand DTPA and has now been adapted as part of a cell surface receptor. A team led by Wolfgang Weber, Professor of Nuclear Medicine at TUM University Hospital, used this concept to engineer an artificial gene that causes cells to express the anticalin receptor "DTPA-R" on their surface. The project was spearheaded by Volker Morath and Katja Fritschle from the Department of Nuclear Medicine, who, along with their team, also developed the matching radioligand for DTPA-R: ¹⁸F-DTPA. The method was tested on CAR T cells in collaboration with immunotherapy expert Dirk Busch, Professor of Medical Microbiology, Immunology and Hygiene at TUM.

In experiments with mice, the researchers were able to demonstrate that the modified cells indeed migrated to the affected diseased tissue and proliferated there. They also showed that the radioligand is rapidly excreted via the kidneys, binds exclusively to cells with the artificial receptor, and does not interfere with other processes in the body. Moreover, the study showed that this approach can also be used to monitor gene therapies in which viruses serve as tools to alter genetic information within cells.

“For several years now, it has been clear that new medical applications like immunotherapies and gene therapies hold tremendous potential,” says Prof. Wolfgang Weber, who led the study. “We believe that we have created a valuable tool that can make such therapies safer by providing better insight into what happens inside the body.” The technique is still in its early stages. Before it can be used in human patients, its safety and efficacy must be verified in clinical trials. Further development toward clinical trial use and commercialization is currently ongoing.

Still, the researchers believe the method can already yield valuable insights for basic research. It is also intended to support animal welfare: If laboratory animals can be continuously monitored during experiments, their numbers could be significantly reduced in the development of new cell and gene therapies.