Engineered T cells targeting solid tumors show promising results in early patient trial

The IMA203 treatment uses T cells engineered to target the PRAME peptide, which is almost exclusively produced by solid tumors and not healthy cells – Image credit copyright Nature Medicine

CANCER DIGEST – April, 27, 2025 – More than half of the melanoma patients, who had failed to respond to standard treatments, responded to a new treatment using genetically engineered T cells, according to a German research team.

Led by professor Martin Wermke, head and first author of the trial, the research team at the National Center for Tumor Diseases (NCT/UCC) in Dresden, Germany conducted the early stage clinical trial of the new treatment, called IMA203, in 40 melanoma patients. Wermke said the results, reported in the April 9, 2025 journal Nature Medicine. proved very encouraging.

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

The results are remarkable in such an early clinical trial primarily aimed at determining safety and optimal dose. In the phase 1 trial involving 40 patients who had not responded to standard therapies including chemotherapy and CAR T cell immunotherapy were given infusions of the newly engineered T cells in two groups.

One group (27 patients) received a minimal dose to test safety. Once shown to be safe the 13 remaining patients received increasing doses to evaluate side effects. All the patients treated with the higher doses experienced side effects, such as fever and skin rash, that was treated with short courses of steroids. 

While the trial did not aim to test the effectiveness of the treatment, the researchers reported that all patients did show a response to the tumor, meaning the cancer stopped growing or shrank, and that the response lasted more than eight months, and in some patients more than two years. This is a significantly longer response time compared to chemotherapy, which typically lasts three to six months. 

The results offer a promising advance in treating solid tumors with engineered T cells. Other engineered T cell immunotherapies such as CAR T-cells have been very successful in treating liquid tumors, such as leukemias and lymphomas, but have been less successful in attacking solid tumors due to the challenges of solely targeting surface antigens on these tumors.

Cell surface antigens are proteins that mark the cell for recognition by the immune system. Some antigens mark a cell as "self," which tells T cells to ignore them, while other antigens label a cell as "foreign," which activates T cells to attack them. 

The new T cell receptor-engineered T cells (TCR T-cells) target both cell surface antigens and intracellular antigens produced by the body’s immune system, called the major histocompatibility complex, or MHC antigens. 

Solid tumor cells produce cell surface antigens that disguise the tumor from being recognized as "foreign" by T cells. However, cancer cells rely on a peptide call PRAME to produce some of these antigens, and the PRAME peptide is almost exclusively produced by cancer cells.

The new treatment uses T cells engineered to target the PRAME peptide. This IMA203 T cell therapy enables the T cells to attack tumor cells in a targeted manner without damaging normal cells. PRAME is produced by many tumors, such as melanoma, ovarian cancer, sarcomas, and lung cancer.

“Based on these results, we can speak of a breakthrough,” Wermke said in a press release,  “For the first time, we have achieved a lasting response in truly common solid tumors. The efficacy of IMA203 goes far beyond what we can achieve with our current chemotherapy and immunotherapy treatments."

Sources: Dresden University Hospital press release and the journal Nature Medicine