ASCO 2026 | The current state and future of TILs and other cell therapies in melanoma
Marco Donia, MD, PhD, Copenhagen University Hospital, Herlev, Denmark, discusses various immunotherapeutic approaches in melnoma, including therapy with tumor-infiltrating lymphocytes (TILs), modified TIL protocols, and leading precision T-cell therapies such as TCR T-cells and CAR-T cells. Dr Donia highlights the different stages of development and approval for these treatments, noting that TILs have received FDA approval, while CAR-T cells are at an early stage in melanoma. This interview took place during the 2026 American Society of Clinical Oncology (ASCO) Meeting in Chicago, IL.
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Transcript
The innovations that probably will expand the role of cell therapy in melanoma are going to be in the number two and number three topics I discussed. Number two is modified TILs. We have several platforms, for example with gene-engineered TILs, that have advantages compared to the original protocol. For example, some of the platforms can reduce the dependency on the interleukin-2, which is the major source of toxicity, or platforms that can improve the efficacy of TIL therapy...
The innovations that probably will expand the role of cell therapy in melanoma are going to be in the number two and number three topics I discussed. Number two is modified TILs. We have several platforms, for example with gene-engineered TILs, that have advantages compared to the original protocol. For example, some of the platforms can reduce the dependency on the interleukin-2, which is the major source of toxicity, or platforms that can improve the efficacy of TIL therapy. The other one, the leading challenger to TIL therapy, is TCR T cells. So gene-engineered cells where we take them from the blood, different from TILs where we have an origin that is a tumor. So we take blood, we engineer immune cells from the blood with a receptor that is going to recognize the tumor and then we infuse the cells back to the same patient. Now this is a precision platform because there is a precise TCR, T-cell receptor, that recognizes a precise antigen. So what is the advantage is that we know what is recognizing. The disadvantage is that typically it’s a single antigen that is recognized compared to the TILs where we have a polyclonal activation. Polyclonal T cells recognize cancer cells from multiple angles. TCR recognizes only one, which also means that cancer cells have to mutate or reduce the expression of only one to escape. This has proven so far to be anyway very effective in some types of melanoma, like for example, uveal melanoma, but also cutaneous melanoma. Uveal melanoma is an absolutely dramatic disease with essentially very little advances in the past year. There is a new drug called Tebentafusp that improved the overall survival still doesn’t cure any patient. We hope the TCR T is gonna do it. One major limitation is that this is gonna be, is right now available in clinical trials only for patients with a certain HLA type that is expressed in about 45% of the European or US population.
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