NCT Supports First Study of a Novel TCR-T Cell Therapy – Clinical Trial to Begin in 2027

Advanced, hard-to-treat cancers are among the leading causes of death worldwide—second only to cardiovascular diseases. While CAR-T cell therapies have already shown remarkable success in treating blood and lymphatic cancers, comparable immunotherapy approaches for solid tumors—such as those in the lungs, bladder, soft tissue, or head and neck—have so far yielded significantly less effective results.

The NCT is now supporting a new therapeutic approach with great potential. The multicenter ToMA4TA1 trial will, for the first time, test a newly developed TCR-T cell therapy in patients with advanced solid tumors. The study will include up to 24 participants and aims to evaluate the therapy’s safety, optimal dosing, and initial signs of efficacy. It is coordinated by NCT Berlin, with participation from the NCT sites in Dresden, Heidelberg, SouthWest, WERA, and West, as well as the Nuremberg Hospital as an external partner. The principal investigator is PD Dr. Antonia Busse at Charité – Universitätsmedizin Berlin, Campus Benjamin Franklin. Charité is also the legal sponsor of the study.

This study is the result of years of research funded by the Federal Ministry for Research, Technology and Space (BMFTR), the Max Delbrück Center for Molecular Medicine (MDC), and the Berlin Institute of Health at Charité (BIH). The clinical trial is made possible through NCT’s newly allocated funding, with a projected start in 2027.

A Milestone for NCT Berlin

The study is based on a joint initiative between Charité and the biotech company Captain T Cell, a successful spin-off from the Max Delbrück Center. “The funding of this study is another important step toward personalized cancer therapy and a major milestone for the development of the newly established NCT site in Berlin, which is taking the scientific lead here,” says Prof. Ulrich Keilholz, spokesperson and managing director of NCT Berlin. He calls the collaboration between Captain T Cell researchers and leading university cancer centers in Germany “exemplary of the NCT’s approach to advancing top-tier cancer research through national cooperation.”

Innovative Therapeutic Approach

The TCR-T cell therapy uses T cells that have been genetically engineered to express a T cell receptor (TCR) that specifically targets the tumor antigen MAGE-A4—a protein found in various solid tumors and considered a promising target for immunotherapy. These engineered T cells can recognize not only surface markers on tumor cells but also hidden intracellular structures. Additionally, the cells have been molecularly modified to survive longer and remain active within the hostile tumor microenvironment.

Another key innovation: The T cells used in the ToMA4TA1 trial were specifically developed and optimized for patients with the HLA-A1 tissue marker. By contrast, the first TCR-T cell therapy recently approved in the U.S.—also targeting MAGE-A4—is only available to patients with the HLA-A2 variant, thereby excluding a significant number of potential patients. The new trial opens up treatment possibilities for this underserved group.

High Relevance for Patients

“This novel approach is highly relevant for patients,” emphasizes Antonia Busse. “In clinical practice, we see many people for whom no established treatment options remain. We urgently need new therapies. Innovative TCR-T cell therapies offer a chance for meaningful therapeutic success—even in cases previously deemed virtually untreatable.”

“The preclinical data are promising and give us hope that we can achieve a substantial therapeutic effect,” adds Dr. Felix Lorenz, CEO and CSO of Captain T Cell. “This is a major milestone for our team—our TCR-T cell therapy will now be used in a clinical trial for the first time. Our goal is to offer new hope to patients with no remaining treatment options.”

Patient Involvement from the Beginning

Ulla Ohlms, spokesperson of the Patient Research Council at NCT Berlin and involved in the study’s development from the start, also underscores the therapy’s importance. “As a patient representative, I don’t need to understand the complex mechanisms of HLA-A1 or MAGE-A4,” she explains. “Our role is to evaluate whether and how this therapy can benefit patients. ToMA4TA1 is a ‘proof of concept’ trial—testing new therapeutic possibilities for patients who have exhausted all other options. That’s what I consider true patient benefit,” says Ohlms.