A groundbreaking development in cancer immunotherapy has emerged from Dresden University Hospital, where researchers have announced promising results from a phase 1 clinical trial utilizing T cell receptor (TCR)-engineered T cells. This innovative approach involves genetically modifying a patient’s own immune cells to specifically recognize and attack tumor cells while sparing healthy tissues. The trial’s primary focus was on advanced solid tumors, a category notoriously resistant to conventional treatments such as chemotherapy and immune checkpoint inhibitors.
At the heart of this research lies IMA203, a newly developed cell therapy designed to target the PRAME peptide. PRAME is a protein abundantly expressed in a wide spectrum of tumors including melanoma, ovarian cancer, sarcomas, and lung cancer, but is minimally or not at all produced by normal, healthy cells. This selective expression of PRAME provides an ideal target, enabling engineered T cells to precisely identify and eradicate cancer cells without causing collateral damage to the patient’s normal tissues—a longstanding challenge in solid tumor oncology.
The clinical trial enrolled 40 patients who had exhausted standard treatment options. These patients had aggressive and advanced tumor diseases, many of which had shown little to no response to previous therapies. Thanks to the incorporation of a high-affinity TCR that recognizes the PRAME peptide presented on tumor cells, the T cells were reprogrammed to seek and destroy tumor cells selectively. This precision targeting marks a significant departure from earlier, less specific immunotherapies which often caused severe systemic side effects.
Results from the study were encouraging: approximately half of the treated patients, who had previously failed standard treatments, demonstrated a meaningful clinical response to IMA203 therapy. Importantly, many responses were durable, lasting not merely months but extending beyond eight months, with some patients still without relapse for over two years. This longevity of response marks a profound improvement compared to traditional chemotherapy options, which generally offer only limited durable benefit lasting a few months at best.
Equally noteworthy, the cell therapy exhibited a favorable safety profile. Patients mainly experienced manageable side effects such as mild to moderate fever and skin rashes, which were transient and resolved without serious complications. The absence of severe immune-related adverse events underscores the specificity and controlled activity of the engineered TCR T cells, a critical factor for broad clinical application in solid tumors.
Professor Martin Wermke, the head of the Early Clinical Trial Unit and the lead author of the study, heralded these findings as a transformative milestone. He emphasized that for the first time, a lasting therapeutic response has been achieved in common solid tumors through engineered T cells. Contrasting this breakthrough with current treatments, Prof. Wermke underscored not only the increased response rates but also the prolonged duration of remission, describing some cases as potentially curative, which holds tremendous promise for patients with historically poor prognoses.
Dresden University Hospital has long been a pioneer in cell therapies, particularly for hematologic malignancies. Professor Martin Bornhäuser, Director of Medical Clinic I and NCT/UCC Dresden, reflected on the historical evolution of the cell therapy program initiated over two decades ago. What was initially tailored toward blood cancers now provides vital infrastructure and expertise necessary to extend cutting-edge cell therapies like IMA203 to patients battling solid tumors, a frontier previously fraught with challenges.
Looking forward, the researchers plan to expand clinical investigations of IMA203 into larger phase 2 and 3 trials, especially focusing on melanoma patients who have failed to respond to conventional immunotherapies and targeted treatments. These upcoming studies aim to validate and potentially establish IMA203 as a new standard therapy for solid tumors, addressing an unmet medical need that affects millions worldwide. The efforts are part of a broader strategic commitment by the NCT/UCC Dresden to develop and test novel cell-based immunotherapies against a variety of challenging cancers.
The project has garnered enthusiastic support from academic leadership. Professor Esther Troost, Dean of TU Dresden’s Faculty of Medicine, lauded the perseverance and dedication of the research team, recognizing the growing prominence of oncology research at the institution. The clinical successes realized through IMA203 serve as compelling evidence that intensive investment in cellular immunotherapies can translate into tangible hope for cancer patients facing limited treatment options.
Moreover, the hospital’s Medical Director, Professor Uwe Platzbecker, highlighted that regulatory approvals for similar cell therapies targeting solid tumors are anticipated imminently. Preparations are underway to ensure that these innovative treatments can be rapidly integrated into clinical practice, maximizing patient access. This proactive stance underscores the hospital’s vision of becoming a leading center for personalized cancer immunotherapy.
Technically, the mechanism of action of IMA203 involves the genetic engineering of patient-derived T cells to express a TCR with high affinity for a PRAME peptide presented in the context of HLA molecules on tumor cell surfaces. Upon infusion back into the patient, these TCR-engineered T cells circulate and home toward tumor sites, where they recognize peptide-HLA complexes and initiate targeted cytotoxicity. This approach combines the specificity of the adaptive immune system with advances in gene editing and cell manufacturing, creating a powerful anti-tumor modality distinct from previous antibody-based or general immune-stimulating methods.
Equally critical to this therapeutic success is the manufacturing infrastructure, which ensures the production of high-quality, standardized TCR-T cell products suitable for patient administration. Dresden University Hospital’s established facilities and expertise in cell processing have enabled seamless translation of this academic innovation into a viable clinical treatment. The sustained collaboration between immunologists, oncologists, genetic engineers, and clinical trial experts has been pivotal in overcoming technical, logistical, and regulatory hurdles.
In summary, the advent of IMA203 represents a paradigm shift in the treatment of solid tumors, demonstrating that TCR-engineered T cell therapies can achieve meaningful and lasting responses with manageable toxicity profiles. As the field of cellular immunotherapy continues to evolve, these findings provide a beacon of hope that could transform cancer care, offering patients durable remissions and the possibility of long-term survival or even cures. The results reported from Dresden University Hospital are a significant step toward realizing the full potential of personalized, immune-based cancer therapies.
Subject of Research: People
Article Title: Research success at Dresden University Hospital: New cell therapy shows promising results in advanced tumor diseases
News Publication Date: 25-Apr-2025
Web References:
DOI 10.1038/s41591-025-03650-6
Image Credits: UKD/Thomas Albrecht
Keywords: T cell receptor-engineered T cells, IMA203, PRAME peptide, solid tumors, immunotherapy, melanoma, cell therapy, clinical trial, Dresden University Hospital, personalized cancer treatment, durable response, cancer immunotherapy
Tags: advanced cancer clinical trials outcomescell therapy for advanced tumorsclinical trial results for solid tumorsDresden University Hospital cancer researchgenetically modified immune cells in cancerimmune system targeting tumor cellsimmunotherapy breakthroughs in cancer treatmentinnovative cancer treatments 2023PRAME peptide targeted therapyprecision oncology and cell therapyT cell receptor engineered T cellstreatment-resistant advanced solid tumors
