In recent years, cell therapies have developed alongside chemotherapy and immunotherapy to become a new pillar in the treatment of patients with blood and lymph gland cancer. In solid tumours, such as skin, lung, or bone and soft tissue cancer (sarcomas), they have not yet proven themselves as a treatment method.

Tumour shrinkage was achieved only in rare cases, but the side effects were all the more severe. An international research group led by scientists from the National Centre for Tumour Diseases (NCT/UCC) in Dresden has now conducted a Phase I clinical trial of a novel cell therapy approach that shows promise for solid tumours.

The results are published in Nature Medicine.

In the Phase I trial involving 40 patients, the research group investigated the use of T cell receptor (TCR)-engineered T cells. Using genetic engineering techniques, the researchers incorporated a kind of target identification into the T cells to enable them to recognise tumour-specific proteins.

The newly tested IMA203 therapy targets the PRAME peptide, which is produced almost exclusively by tumours and not by healthy tissue. This enables the T cells to attack tumour cells in a targeted manner without damaging normal cells. PRAME is produced by many tumours, such as melanoma, ovarian cancer, sarcomas, and lung cancer.

A good half of the people treated who had not responded previously to standard therapies responded to the new therapy. The majority of them even responded over a period of eight months or several years.

Compared to chemotherapy, which usually lasts three to six months, this is a significant advancement in treatment. The cell therapy was also well tolerated. Side effects such as fever or skin rash were mostly mild to moderate and only temporary.

"Based on these results, we can speak of a breakthrough," says Prof. Martin Wermke, head and first author of the trial.

"For the first time, we have achieved a lasting response in truly common solid tumours. The efficacy of IMA203 goes far beyond what we can achieve with our current chemotherapy and immunotherapy treatments.

"Not only do we have significantly more patients responding to treatment, but the effect is also lasting much longer. We now have patients who have not had a relapse of their tumour disease more than two years after receiving IMA203. Some of these patients may even have been permanently cured of their cancer."

"Cell therapies are virtually part of the DNA of the Dresden University Hospital," adds Prof. Martin Bornhäuser, Director of Medical Clinic I and the NCT/UCC Dresden. He began setting up the cell therapy program at Dresden University of Medicine more than two decades ago.

"The infrastructure we have developed over many years, primarily for patients with blood and lymph gland cancer, will help us in the future to offer innovative cell therapies such as IMA203 to as many patients as possible who are suffering from solid tumours."

In a next step, IMA203 could be used in a larger trial in patients with melanoma who have not responded to conventional immune and targeted therapies. The NCT/UCC Dresden is testing other cell therapies for other types of skin cancer and lung cancer.

"I would like to congratulate the scientists on their years of perseverance and the success they have now achieved," said Prof. Esther Troost, Dean of TU Dresden's Faculty of Medicine. "The Faculty of Medicine's focus on oncology is bearing fruit and now gives cancer patients justified hope."

Prof. Uwe Platzbecker, Medical Director of the University Hospital, said, "The first approvals for cell therapies to treat solid tumours are already in the pipeline, and we are working hard to prepare for these. Our goal is to be able to offer these innovative therapies to as many patients as possible."

More information: Martin Wermke et al, Autologous T cell therapy for PRAME+ advanced solid tumours in HLA-A*02+ patients: a phase 1 trial, Nature Medicine (2025). DOI: 10.1038/s41591-025-03650-6

Provided by Nationales Centrum für Tumorerkrankungen (NCT/UCC) Dresden

--Nationales Centrum für Tumorerkrankungen (NCT/UCC) Dresden