Tumour-infiltrating lymphocyte therapy for patients with advanced-stage melanoma

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.Despite dramatic progress over the past decade, only around 50% of patients with advanced-stage melanoma derive durable benefit from immune-checkpoint inhibitors (ICIs) and/or BRAF and MEK (BRAF/MEK) inhibitors. Over the past few years, adoptive cell therapy with tumour-infiltrating lymphocytes (TILs) has demonstrated encouraging efficacy including in patients with disease progression on ICIs or BRAF/MEK inhibitors. In this Review, the authors summarize the role of TIL therapies in the management of these patients and describe future research strategies that might improve safety or efficacy.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.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.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.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.