Abstract
Immunotherapy with immune-checkpoint inhibitors (ICIs) and targeted therapy with BRAF and MEK inhibitors have revolutionized the treatment of melanoma over the past decade. Despite these breakthroughs, the 5-year survival rate of patients with advanced-stage melanoma is at most 50%, emphasizing the need for additional therapeutic strategies. Adoptive cell therapy with tumour-infiltrating lymphocytes (TILs) is a therapeutic modality that has, in the past few years, demonstrated long-term clinical benefit in phase II/III trials involving patients with advanced-stage melanoma, including those with disease progression on ICIs and/or BRAF/MEK inhibitors. In this Review, we summarize the current status of TIL therapies for patients with advanced-stage melanoma, including potential upcoming marketing authorization, the characteristics of TIL therapy products, as well as future strategies that are expected to increase the efficacy of this promising cellular immunotherapy.
Key points
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Tumour-infiltrating lymphocyte (TIL) therapy shows consistent clinical activity in patients with advanced-stage melanoma, including after disease progression on or after immune-checkpoint inhibitors and BRAF plus MEK inhibitors, and is manageable in most patients.
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Selection of tumour-reactive T cells and improvements in T cell function during the manufacturing process are expected to further improve the clinical activity of TIL therapy while limiting toxicity.
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Further clinical implementation of TIL therapy will require the establishment of infrastructure for centralized TIL production or point-of-care manufacturing, as well as treatment by an experienced medical team.
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Centralized TIL production and treatment of patients at dedicated centres might be important to enhance the clinical feasibility of TIL therapy and will drive further technological innovation.
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S.K., T.T.P.S. and J.B.A.G.H. researched data for the manuscript. All authors made a substantial contribution to discussions of content. S.K., T.T.P.S. and J.B.A.G.H. wrote the manuscript and all authors edited and/or reviewed the manuscript before submission.
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S.K. has acted as an adviser of Regeneron. T.N.S. has acted as an adviser of Allogene Therapeutics, Asher Therapeutics, Celsius, Merus, Neogene Therapeutics and Scenic Biotech; is a stockholder in Allogene Therapeutics, Asher Therapeutics, Cell Control, Celsius, Merus and Scenic Biotech; and is a venture partner at Third Rock Ventures. J.B.A.G.H. has acted as an adviser of Achilles Therapeutics, BioNTech, Bristol Myers Squibb, CureVac, Gadeta, Immunocore, Instil Bio, Iovance Bio, Ipsen, Merck Serono, Molecular Partners, MSD, Neogene Therapeutics, Novartis, Pfizer, Roche/Genentech, Sanofi, Scenic, Seattle Genetics, Third Rock Ventures and T-Knife, and has received research grants from Amgen, Asher Bio, BioNTech, Bristol Myers Squibb, MSD, Novartis and Sastra Cell Therapy. T.T.P.S. declares no competing interests.
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Klobuch, S., Seijkens, T.T.P., Schumacher, T.N. et al. Tumour-infiltrating lymphocyte therapy for patients with advanced-stage melanoma. Nat Rev Clin Oncol 21, 173–184 (2024). https://doi.org/10.1038/s41571-023-00848-w
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DOI: https://doi.org/10.1038/s41571-023-00848-w