Advanced metastatic melanoma was long considered barely treatable. Immunotherapies have improved survival dramatically since 2011, but in a substantial share of patients they still do not work. New cell therapy approaches are meant to close that gap. The first has already been approved in the United States. In Europe, research is advancing along several paths at once.
TIL Therapy: Already in Use in the US
In February 2024 the FDA approved lifileucel, brand name Amtagvi, as the first tumor-infiltrating lymphocyte therapy for advanced melanoma. The principle: doctors extract the patient's own T lymphocytes directly from the tumour, where they have already begun fighting the cancer. These cells are then multiplied in the lab for several weeks and returned to the patient in large numbers.
The overall response rate in the registration trial was 31.5 percent. For patients who have exhausted all other treatment lines, this is an option that did not previously exist. The therapy is complex and expensive because it must be manufactured individually for each patient. It is now being established in specialized cancer centres across the US. The European Medicines Agency is reviewing it.
A Discovery From April 2026
A paper published in early April 2026 describes a finding that could fundamentally improve the effectiveness of cell therapies against solid tumours like melanoma. Cancer cells possess their own cellular alarm system, originally meant to warn other immune cells. That system can be exploited to steer CAR-T cells, genetically modified immune cells, more precisely into the tumour. In early laboratory experiments, CAR-T effectiveness improved markedly with this approach.
This matters because CAR-T therapies are now standard against blood cancers but have so far barely worked against solid tumours. Dense tumour tissue and a hostile immune environment prevented CAR-T cells from entering effectively. The new approach may overcome this barrier. The research is still at the preclinical stage.
TCR-T Cells as an Alternative
In parallel, TCR-T cell therapy is developing. Unlike CAR-T cells, TCR-T cells use the natural T-cell receptor to recognize cancer cells. This allows them to detect proteins inside the cell, not just surface markers. Early clinical trials with the candidate IMA203 showed tumour regressions in a portion of treated melanoma patients with metastases. Larger clinical trials on efficacy and safety are underway.
Nine Years of Immunotherapy Data
At the annual ESMO Congress of the European Society for Medical Oncology in autumn 2025 in Berlin, researchers presented long-term data from the CheckMate-238 trial. Nine years out, patients treated with the checkpoint inhibitor nivolumab after surgical removal of a melanoma still showed better survival than the comparison group. The takeaway for practice: the benefit of immunotherapy holds up over the long term.