Innovative PET Technique Enables Monitoring of Engineered T Cells in Immunotherapy

Recent advancements at the Technical University of Munich (TUM) have paved the way for new ways to visualize and track engineered immune cells during immunotherapy treatments. Researchers have developed a novel positron emission tomography (PET)-based method that allows for real-time monitoring of modified T cells within the body, significantly enhancing our understanding of their behavior in cancer therapies.

In modern immunotherapy, especially CAR-T-cell therapy, immune cells are extracted from patients, genetically modified to target specific tumor antigens, and then reintroduced into the body to attack cancer cells. A critical challenge has been the inability to precisely observe how these cells migrate, proliferate, and act within the patient, raising concerns about unpredictable behavior and potential off-target effects.

To address this, the TUM team introduced a second artificial receptor into the engineered T cells. This receptor, based on a specially designed protein known as an anticalin, binds to a non-toxic radioactive contrast agent called a radioligand. When injected into the patient, the radioligand selectively attaches to the modified cells expressing this receptor, rendering them visible on PET scans. This method provides a non-invasive and specific way to track the location, movement, and proliferation of therapeutic cells in vivo.

The research, led by experts including Wolfgang Weber and Volker Morath, involved engineering cells to express the DTPA-R receptor, which binds to a radioligand developed in collaboration with scientists like Arne Skerra, a pioneer in protein engineering. The experiments conducted on mice demonstrated that the modified cells successfully migrated to tumor tissue, multiplied there, and that the radioligand was quickly cleared from the body, only binding to the target cells without interfering with normal functions.

This innovative approach not only facilitates better monitoring of cell therapies but also opens doors for tracking gene therapies using viral vectors. Its development could improve the safety and efficacy of future treatments, allowing clinicians to observe and adapt therapies in real time.

Prof. Weber emphasizes that this technology holds the potential to make complex cellular and gene therapies safer, providing valuable insights into the biology of these treatments. Before human application, further validation through clinical trials is essential. Nonetheless, the method promises to significantly advance basic research, reduce reliance on animal testing, and improve patient outcomes in the long run.

The researchers’ findings were published in Nature Biomedical Engineering, marking a significant step forward in personalized medicine and targeted cancer therapies.